Vaccines

22 pages, 583 KiB

Open AccessCommentary

Accelerating Global Measles and Rubella Eradication—Saving Millions of Lives, Preventing Disability, and Averting the Next Pandemic

by David N. Durrheim, Jon K. Andrus, Shahina Tabassum, David Githanga, Mira Kojouharova and Nadia Talab

Vaccines 2024, 12(6), 699; https://doi.org/10.3390/vaccines12060699 - 20 Jun 2024

Cited by 1 | Viewed by 1440

Abstract

No vaccine has been more effective in reducing disease burden, especially in preventing child deaths, than measles-containing vaccine. The return on investment makes measles-containing vaccine one of the most cost-effective public health measures available. Exhaustive reviews of biological, technical, economic and programmatic evidence [...] Read more.

No vaccine has been more effective in reducing disease burden, especially in preventing child deaths, than measles-containing vaccine. The return on investment makes measles-containing vaccine one of the most cost-effective public health measures available. Exhaustive reviews of biological, technical, economic and programmatic evidence have concluded that measles can and should be eradicated, and by including rubella antigen in measles-containing vaccine, congenital rubella syndrome will also be eradicated. All World Health Organisation Regions have pledged to achieve measles elimination. Unfortunately, not all countries and global partners have demonstrated an appropriate commitment to these laudable public health goals, and the negative impact of the COVID-19 pandemic on coverage rates has been profound. Unsurprisingly, large disruptive outbreaks are already occurring in many countries with a global epidemic curve ominously similar to that of 2018/2019 emerging. The Immunization Agenda 2030 will fail dismally unless measles and rubella eradication efforts are accelerated. Over half of all member states have been verified to have eliminated rubella and endemic rubella transmission has not been re-established in any country to date. In 2023, 84 countries and areas were verified to have sustained elimination of measles. However, without a global target, this success will be difficult to sustain. Now is the time for a global eradication goal and commitment by the World Health Assembly. Having a galvanising goal, with a shared call for action, will demand adequate resourcing from every country government and global partners. Greater coordination across countries and regions will be necessary. Measles, rubella and congenital rubella syndrome eradication should not remain just a technically feasible possibility but rather be completed to ensure that future generations of children do not live under the shadow of preventable childhood death and lifelong disability. Full article

(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)

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2 pages, 117 KiB

Open AccessEditorial

Addressing the Dangerous Consequences of the Resurgence of Measles and Rubella: The Critical Need for a Global Target

by Jon Kim Andrus

Vaccines 2024, 12(6), 698; https://doi.org/10.3390/vaccines12060698 - 20 Jun 2024

Viewed by 712

Abstract

I am delighted and honored to be Guest Editor of this Vaccines Special Issue on measles and rubella elimination [...] Full article

(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)

12 pages, 236 KiB

Open AccessReview

Measles and Rubella Diagnostic and Classification Challenges in Near- and Post-Elimination Countries

by Thomas D. Filardo, Stephen N. Crooke, Bettina Bankamp, Kelley Raines, Adria D. Mathis, Tatiana M. Lanzieri, R. Suzanne Beard, Ludmila Perelygina, David E. Sugerman and Paul A. Rota

Vaccines 2024, 12(6), 697; https://doi.org/10.3390/vaccines12060697 - 20 Jun 2024

Viewed by 975

Abstract

Measles and rubella are vaccine-preventable viral diseases and can be prevented by safe, highly effective vaccination with measles- and rubella-containing vaccines. Given the myriad causes of febrile exanthems, laboratory surveillance for both measles and rubella is important to document the incidence of these [...] Read more.

Measles and rubella are vaccine-preventable viral diseases and can be prevented by safe, highly effective vaccination with measles- and rubella-containing vaccines. Given the myriad causes of febrile exanthems, laboratory surveillance for both measles and rubella is important to document the incidence of these diseases and to track the progress and maintenance of elimination in near- and post-elimination settings. Diagnostic challenges can hinder effective surveillance and classification challenges can hinder efforts to demonstrate achievement or maintenance of elimination. In this report, we review diagnostic and classification challenges for measles and rubella in near- and post-elimination settings. Full article

(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)

20 pages, 1439 KiB

Open AccessArticle

Progress and Challenges in Measles and Rubella Elimination in the WHO European Region

by Mark Muscat, Myriam Ben Mamou, Catharina Reynen-de Kat, Dragan Jankovic, José Hagan, Simarjit Singh and Siddhartha Sankar Datta

Vaccines 2024, 12(6), 696; https://doi.org/10.3390/vaccines12060696 - 20 Jun 2024

Cited by 2 | Viewed by 1549

Abstract

The elimination of both measles and rubella remains a priority for all 53 Member States of the World Health Organization (WHO) European Region. To provide an update on the epidemiological status of measles and rubella in the Region, we reviewed surveillance data on [...] Read more.

The elimination of both measles and rubella remains a priority for all 53 Member States of the World Health Organization (WHO) European Region. To provide an update on the epidemiological status of measles and rubella in the Region, we reviewed surveillance data on both diseases for 2023 submitted monthly by national surveillance institutions. We analyzed the cases of measles and rubella for 2023 by age group, case classification, vaccination, hospitalization, and importation status and report on measles-related deaths. In 2023, 60,860 measles cases, including 13 fatal cases, were reported in 41 countries. Most cases (95%; n = 57,584) were reported by six countries: Azerbaijan, Kazakhstan, Kyrgyzstan, Romania, the Russian Federation, and Türkiye. Of the 60,848 cases with data on age, 19,137 (31%) were 1–4 years old and 12,838 (21%) were 5–9 years old. A total of 10,412 (17%) were 20 years and older. The genotypes identified in the Region were largely dominated by D8 variants (n = 1357) and the remainder were B3 variants (n = 221). In 2023, 345 rubella cases were reported by 17 countries, mostly from Poland, Kyrgyzstan, Tajikistan, Türkiye, and Ukraine. A total of 262 cases (76%) were classified as clinically compatible and 79 (23%) were laboratory-confirmed. To achieve the elimination of measles and rubella in the Region, political commitment needs to be revived to enable urgent efforts to increase vaccination coverage, improve surveillance and outbreak preparedness, and respond immediately to outbreaks. Full article

(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)

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12 pages, 2248 KiB

Open AccessArticle

Breakthrough Measles among Vaccinated Adults Born during the Post-Soviet Transition Period in Mongolia

by José E. Hagan, Stephen N. Crooke, Nyamaa Gunregjav, Sun B. Sowers, Sara Mercader, Carole J. Hickman, Mick N. Mulders, Roberta Pastore, Yoshihiro Takashima, David N. Durrheim, James L. Goodson and Paul A. Rota

Vaccines 2024, 12(6), 695; https://doi.org/10.3390/vaccines12060695 - 20 Jun 2024

Viewed by 1050

Abstract

Mongolia experienced a nationwide measles outbreak during 1 March 2015–31 December 2016, with 49,077 cases reported to the WHO; many were among vaccinated young adults, suggesting a possible role of vaccine failure. Advanced laboratory methods, coupled with detailed epidemiological investigations, can help classify [...] Read more.

Mongolia experienced a nationwide measles outbreak during 1 March 2015–31 December 2016, with 49,077 cases reported to the WHO; many were among vaccinated young adults, suggesting a possible role of vaccine failure. Advanced laboratory methods, coupled with detailed epidemiological investigations, can help classify cases as vaccine failure, failure to vaccinate, or both. In this report, we conducted a study of cases to identify risk factors for breakthrough infection for a subset of laboratory-confirmed measles cases. Of the 193 cases analyzed, only 19 (9.8%) reported measles vaccination history, and 170 (88%) were uncertain. Measles-specific IgG avidity testing classified 120 (62%) cases as low IgG avidity, indicating no prior exposure to measles. Ten of these cases with low IgG avidity had a history of measles vaccination, indicating primary vaccine failure. Overall, sixty cases (31%) had high IgG avidity, indicating breakthrough infection after prior exposure to measles antigen through vaccination or natural infection, but the IgG avidity results were highly age-dependent. This study found that among young children aged 9 months–5 years, breakthrough infection was rare (4/82, 5%); however, among young adults aged 15–25 years, breakthrough infection due to secondary vaccine failure (SVF) occurred on a large scale during this outbreak, accounting for the majority of cases (42/69 cases, 61%). The study found that large-scale secondary vaccine failure occurred in Mongolia, which highlights the potential for sustained outbreaks in post-elimination settings due to “hidden” cohorts of young adults who may have experienced waning immunity. This phenomenon may have implications for the sustainability of measles elimination in countries that remain vulnerable to the importation of the virus from areas where it is still endemic. Until global measles elimination is achieved, enhanced surveillance and preparedness for future outbreaks in post- or peri-elimination countries may be required. Full article

(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)

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18 pages, 590 KiB

Open AccessReview

A World without Measles and Rubella: Addressing the Challenge of Vaccine Hesitancy

by David M. Higgins and Sean T. O’Leary

Vaccines 2024, 12(6), 694; https://doi.org/10.3390/vaccines12060694 - 20 Jun 2024

Cited by 1 | Viewed by 1717

Abstract

The worldwide elimination of measles and rubella is feasible, but not without overcoming the substantial challenge of vaccine hesitancy. This challenge is complicated by the spread of misinformation and disinformation fueled by rapidly progressing technologies and evolving forms of online communication. The recent [...] Read more.

The worldwide elimination of measles and rubella is feasible, but not without overcoming the substantial challenge of vaccine hesitancy. This challenge is complicated by the spread of misinformation and disinformation fueled by rapidly progressing technologies and evolving forms of online communication. The recent COVID-19 pandemic has only added further complexity to this challenge. However, considerable progress has been made in understanding the scope of the problem and the complex factors that influence vaccine hesitancy. Our understanding of evidence-based strategies for addressing vaccine hesitancy has grown significantly, including evidence for effective communication and behavioral interventions. In this article, we review measles and rubella vaccines and vaccine hesitancy. We then provide an overview of evidence-based strategies for addressing vaccine hesitancy, including communication strategies and behavioral interventions. This article is relevant to healthcare professionals, health system leaders, public health professionals, policymakers, community leaders, and any individuals who have a role in addressing vaccine hesitancy in their communities. Finally, we review future directions and major areas of research need. Full article

(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)

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7 pages, 190 KiB

Open AccessCommentary

Evolution and Contribution of a Global Partnership against Measles and Rubella, 2001–2023

by Peter Strebel, Mark Grabowsky, Edward Hoekstra, Andrea Gay and Stephen Cochi

Vaccines 2024, 12(6), 693; https://doi.org/10.3390/vaccines12060693 - 20 Jun 2024

Cited by 3 | Viewed by 1156

Abstract

This article describes the arc of global measles and rubella elimination since 2000 from the perspective of the founding partners of the Measles Initiative. The Measles Initiative was formed in 2001 as a partnership among the American Red Cross, the Centers for Disease [...] Read more.

This article describes the arc of global measles and rubella elimination since 2000 from the perspective of the founding partners of the Measles Initiative. The Measles Initiative was formed in 2001 as a partnership among the American Red Cross, the Centers for Disease Control and Prevention, UNICEF, the United Nations Foundation, and the World Health Organization with the aim to reduce measles deaths in low-income countries. Recognizing rubella as the leading infectious disease cause of congenital abnormalities globally and achievement of measles and rubella elimination in the region of the Americas, the partnership was renamed the Measles and Rubella Initiative (MRI) in 2012. The goals of the MRI were at least a 95% reduction in global measles mortality and elimination of measles and rubella in at least five of the six WHO regions. In January 2023, the membership of the partnership was expanded to include the Bill and Melinda Gates Foundation (BMGF) and Gavi the Vaccine Alliance, and its name changed to the IA2030 Measles and Rubella Partnership. We describe the role the partnership has had in measles partner effectiveness and its impact on measles and rubella disease burden, including how the partnership has strategically adapted to the evolving immunization landscape. We conclude with lessons learned regarding the role global partnerships can play in furthering the impact of disease control programs within the current global immunization environment. Full article

(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)

7 pages, 226 KiB

Open AccessCommentary

The Case for Assessing the Drivers of Measles Vaccine Uptake

by Jessica Kaufman, Ashleigh Rak, Sophia Vasiliadis, Navrit Brar, Eeman Atif, Jennifer White, Margie Danchin and David N. Durrheim

Vaccines 2024, 12(6), 692; https://doi.org/10.3390/vaccines12060692 - 20 Jun 2024

Viewed by 1302

Abstract

Global measles cases are on the rise following disruptions to routine immunisation programs during the COVID-19 pandemic, with devastating consequences. According to the World Health Organization, the behavioural and social drivers of vaccination include what people think and feel about vaccines, social processes, [...] Read more.

Global measles cases are on the rise following disruptions to routine immunisation programs during the COVID-19 pandemic, with devastating consequences. According to the World Health Organization, the behavioural and social drivers of vaccination include what people think and feel about vaccines, social processes, motivation to vaccinate and practical barriers to vaccination. However, the drivers of measles vaccine uptake are not necessarily the same as those for other childhood vaccines, and we lack data on how these drivers specifically have changed during and since the COVID-19 pandemic. Without accurately measuring the behavioural and social drivers for measles vaccination, and ideally measuring them serially over time, countries cannot design, target and implement interventions that effectively increase and sustain measles vaccine coverage. This paper outlines what is and is not known about the behavioural and social drivers of measles vaccination and provides recommendations for improving their post-pandemic assessment. Full article

(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)

20 pages, 2466 KiB

Open AccessArticle

Determinants of Systemic SARS-CoV-2-Specific Antibody Responses to Infection and to Vaccination: A Secondary Analysis of Randomised Controlled Trial Data

by Juana Claus, Thijs ten Doesschate, Esther Taks, Priya A. Debisarun, Gaby Smits, Rob van Binnendijk, Fiona van der Klis, Lilly M. Verhagen, Marien I. de Jonge, Marc J. M. Bonten, Mihai G. Netea and Janneke H. H. M. van de Wijgert

Vaccines 2024, 12(6), 691; https://doi.org/10.3390/vaccines12060691 - 20 Jun 2024

Viewed by 1017

Abstract

SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naïve Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the [...] Read more.

SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naïve Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the one-year follow-up. We assessed determinants of systemic anti-S1 and anti-N immunoglobulin type G (IgG) responses using trial data. Participants were randomised to BCG or placebo vaccination, reported daily symptoms, SARS-CoV-2 test results, and COVID-19 vaccinations, and donated blood for SARS-CoV-2 serology at two time points. In the 970 participants, anti-S1 geometric mean antibody concentrations (GMCs) were much higher than anti-N GMCs. Anti-S1 GMCs significantly increased with increasing number of immune events (SARS-CoV-2 infection or COVID-19 vaccination): 104.7 international units (IU)/mL, 955.0 IU/mL, and 2290.9 IU/mL for one, two, and three immune events, respectively (p < 0.001). In adjusted multivariable linear regression models, anti-S1 and anti-N log₁₀ concentrations were significantly associated with infection severity, and anti-S1 log₁₀ concentration with COVID-19 vaccine type/dose. In univariable models, anti-N log₁₀ concentration was also significantly associated with acute infection duration, and severity and duration of individual symptoms. Antibody concentrations were not associated with long COVID or long-term loss of smell/taste. Full article

(This article belongs to the Section Epidemiology)

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12 pages, 499 KiB

Open AccessReview

Sustaining the Elimination of Measles, Rubella and Congenital Rubella Syndrome in the Americas, 2019–2023: From Challenges to Opportunities

by Gloria Rey-Benito, Desirée Pastor, Alvaro Whittembury, Regina Durón, Carmelita Pacis-Tirso, Pamela Bravo-Alcántara, Claudia Ortiz and Jon Andrus

Vaccines 2024, 12(6), 690; https://doi.org/10.3390/vaccines12060690 - 20 Jun 2024

Cited by 2 | Viewed by 1163

Abstract

This report reviews national data from all Member States on measles, rubella, and congenital rubella syndrome (CRS) elimination in the Region of the Americas during 2019–2023. It includes an analysis of compliance with vaccination coverage, surveillance indicators, and measles outbreaks, as well as [...] Read more.

This report reviews national data from all Member States on measles, rubella, and congenital rubella syndrome (CRS) elimination in the Region of the Americas during 2019–2023. It includes an analysis of compliance with vaccination coverage, surveillance indicators, and measles outbreaks, as well as an analysis of the response capacity of the laboratory network and a country case study that meets all indicators. The sources of information were the integrated epidemiological surveillance system for measles and rubella of the Pan American Health Organization (PAHO)/World Health Organization (WHO) and the Joint Reporting Form (eJRF), among others. From 2020 to 2022, regional coverage with first (MMR-1) and second doses (MMR-2) decreased to rates below 90%. The regional suspected case notification rate was maintained above the minimum expected 2.0 suspect cases per 100,000 population, except in 2021. During 2019 to 2023, 18 countries experienced outbreaks, with two of the outbreaks resulting in re-established endemic transmission. In conclusion, two countries in the Americas have not maintained measles elimination, but by the end of 2023 no country showed endemic measles transmission. One of the countries that lost its certification of elimination in 2018 managed to be reverified in 2023; the other is pending reverification. All countries maintained rubella elimination. Despite these challenges, the sustainability of the elimination of these diseases remains a health priority in the Region. Full article

(This article belongs to the Special Issue A World without Measles and Rubella: Meeting the Regional Elimination Targets on the Path to Global Eradication)

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22 pages, 3340 KiB

Open AccessArticle

Vaccination with a Human Papillomavirus L2 Multimer Provides Broad Protection against 17 Human Papillomavirus Types in the Mouse Cervicovaginal Challenge Model

by Zhenwei Han, Shen Wang, Ting Mu, Ping Zhao, Lingli Song, Ying Zhang, Jin Zhao, Wen Yin, Yue Wu, Huan Wang, Bo Gong, Min Ji, Richard B. S. Roden, Yanping Yang, Michel Klein and Ke Wu

Vaccines 2024, 12(6), 689; https://doi.org/10.3390/vaccines12060689 - 20 Jun 2024

Viewed by 4193

Abstract

Human papillomavirus (HPV) is a prevalent cause of mucosal and cutaneous infections and underlying conditions ranging from benign warts to anogenital and oropharyngeal cancers affecting both males and females, notably cervical cancer. Cervical cancer is the fourth leading cause of cancer deaths among [...] Read more.

Human papillomavirus (HPV) is a prevalent cause of mucosal and cutaneous infections and underlying conditions ranging from benign warts to anogenital and oropharyngeal cancers affecting both males and females, notably cervical cancer. Cervical cancer is the fourth leading cause of cancer deaths among women globally and is the most impactful in low- and middle-income countries (LMICs), where the costs of screening and licensed L1-based HPV vaccines pose significant barriers to comprehensive administration. Additionally, the licensed L1-based HPV vaccines fail to protect against all oncogenic HPV types. This study generated three independent lots of an L2-based target antigen (LBTA), which was engineered from conserved linear L2-protective epitopes (aa11–88) from five human alphapapillomavirus genotypes in E. coli under cGMP conditions and adjuvanted with aluminum phosphate. Vaccination of rabbits with LBTA generated high neutralizing antibody titers against all 17 HPV types tested, surpassing the nine types covered by Gardasil^®9. Passive transfer of naïve mice with LBTA antiserum revealed its capacity to confer protection against vaginal challenge with all 17 αHPV types tested. LBTA shows stability at room temperature over >1 month. Standard in vitro and in vivo toxicology studies suggest a promising safety profile. These findings suggest LBTA’s promise as a next-generation vaccine with comprehensive coverage aimed at reducing the economic and healthcare burden of cervical and other HPV+ cancers in LMICs, and it has received regulatory approval for a first-in-human clinical study (NCT05672966). Full article

(This article belongs to the Special Issue Human Papillomavirus Vaccine against Cervical Cancer: New Usage Strategies and Coverage Issues)

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13 pages, 240 KiB

Open AccessArticle

COVID-19 Booster Vaccination Status and Long COVID in the United States: A Nationally Representative Cross-Sectional Study

by Jamie L. Romeiser and Kelsey Schoeneck

Vaccines 2024, 12(6), 688; https://doi.org/10.3390/vaccines12060688 - 20 Jun 2024

Cited by 1 | Viewed by 1185

Abstract

Early studies have found that the initial COVID-19 vaccination series was protective against severe symptoms and long COVID. However, few studies have explored the association of booster doses on severe disease outcomes and long COVID. This cross-sectional analysis used data from the 2022 [...] Read more.

Early studies have found that the initial COVID-19 vaccination series was protective against severe symptoms and long COVID. However, few studies have explored the association of booster doses on severe disease outcomes and long COVID. This cross-sectional analysis used data from the 2022 US National Health Interview Survey data to investigate how vaccination status correlates with COVID-19 infection severity and long COVID among previously infected individuals. Participants were categorized into three groups: those who had received at least one booster, those with only the initial complete vaccination series, and those with either an incomplete series or no vaccinations. Out of 9521 survey respondents who reported a past positive COVID-19 test, 51.2% experienced moderate/severe infections, and 17.6% experienced long COVID. Multivariable regression models revealed that receiving at least one booster shot was associated with lower odds of experiencing moderate/severe symptoms (aOR = 0.78, p < 0.001) compared to those unvaccinated or with an incomplete series. Additionally, having at least one booster reduced long COVID odds by 24% (aOR = 0.76, p = 0.003). Completing only the primary vaccine series did not significantly decrease the likelihood of severe illness or long COVID. These findings support the continued promotion of booster vaccinations to mitigate long COVID risks in vulnerable populations. Full article

(This article belongs to the Section COVID-19 Vaccines and Vaccination)

21 pages, 3027 KiB

Open AccessArticle

The JMU-SalVac-System: A Novel, Versatile Approach to Oral Live Vaccine Development

by Andreas Iwanowitsch, Joachim Diessner, Birgit Bergmann and Thomas Rudel

Vaccines 2024, 12(6), 687; https://doi.org/10.3390/vaccines12060687 - 20 Jun 2024

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Abstract

Salmonella enterica Serovar Typhi Ty21a (Ty21a) is the only licensed oral vaccine against typhoid fever. Due to its excellent safety profile, it has been used as a promising vector strain for the expression of heterologous antigens for mucosal immunization. As the efficacy of [...] Read more.

Salmonella enterica Serovar Typhi Ty21a (Ty21a) is the only licensed oral vaccine against typhoid fever. Due to its excellent safety profile, it has been used as a promising vector strain for the expression of heterologous antigens for mucosal immunization. As the efficacy of any bacterial live vector vaccine correlates with its ability to express and present sufficient antigen, the genes for antigen expression are traditionally located on plasmids with antibiotic resistance genes for stabilization. However, for use in humans, antibiotic selection of plasmids is not applicable, leading to segregational loss of the antigen-producing plasmid. Therefore, we developed an oral Ty21a-based vaccine platform technology, the JMU-SalVac-system (Julius-Maximilians-Universität Würzburg) in which the antigen delivery plasmids (pSalVac-plasmid-series) are stabilized by a ΔtyrS/tyrS⁺-based balanced-lethal system (BLS). The system is made up of the chromosomal knockout of the essential tyrosyl-tRNA-synthetase gene (tyrS) and the in trans complementation of tyrS on the pSalVac-plasmid. Further novel functional features of the pSalVac-plasmids are the presence of two different expression cassettes for the expression of protein antigens. In this study, we present the construction of vaccine strains with BLS plasmids for antigen expression. The expression of cytosolic and secreted mRFP and cholera toxin subunit B (CTB) proteins as model antigens is used to demonstrate the versatility of the approach. As proof of concept, we show the induction of previously described in vivo inducible promoters cloned into pSalVac-plasmids during infection of primary macrophages and demonstrate the expression of model vaccine antigens in these relevant human target cells. Therefore, antigen delivery strains developed with the JMU-SalVac technology are promising, safe and stable vaccine strains to be used against mucosal infections in humans. Full article

(This article belongs to the Special Issue Advances in Oral Vaccine Development)

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15 pages, 1987 KiB

Open AccessArticle

Immune Responses and Protection Profiles in Mice Induced by Subunit Vaccine Candidates Based on the Extracellular Domain Antigen of Respiratory Syncytial Virus G Protein Combined with Different Adjuvants

by Ruiwen Han, Tangqi Wang, Xueting Cheng, Jialuo Bing, Jia Li, Yao Deng, Xuchang Shan, Xuejie Zhang, Donghong Wang, Shucai Sun and Wenjie Tan

Vaccines 2024, 12(6), 686; https://doi.org/10.3390/vaccines12060686 - 19 Jun 2024

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Abstract

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease of infants and older people. There is an urgent need for safe and effective vaccines against RSV infection. In this study, we analyzed the effects of the immune response [...] Read more.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease of infants and older people. There is an urgent need for safe and effective vaccines against RSV infection. In this study, we analyzed the effects of the immune response and protection with the RSV recombinant G protein extracellular domain (G^ecto) combined with various adjuvants as novel subunit vaccines in mice. All groups receiving RSV G^ecto combined with adjuvants exhibited robust humoral and cellular immunity compared to those receiving an adjuvant alone or inactivated RSV vaccine. The greatest effect was observed in mice receiving G^ecto combined with a CpG ODN + Alum salt adjuvant, resulting in the highest production of neutralizing antibodies against both RSV A and B subtypes, G-specific IgG and IFN-γ production in splenocytes, and interleukin-2 and interferon-γ expression in CD4⁺ T cells. Significant humoral and cellular immune responses were observed in mice immunized with G^ecto combined with AddaS03™ or cyclosporin A adjuvants. The vaccine containing the AddaS03™ adjuvant showed significantly high expression of interleukin-4 in CD4⁺ T cells. Cross-protection against a challenge with either RSV A or B subtypes was observed in the G^ecto plus adjuvant groups, resulting in a significant decrease in viral load and reduced pathological damage in the mouse lungs. These findings offer valuable insights into the development and application of recombinant RSV G-subunit vaccines with adjuvants. Full article

(This article belongs to the Section Vaccine Adjuvants)

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14 pages, 2243 KiB

Open AccessArticle

Field Trials of Live and Inactivated Camelpox Vaccines in Kazakhstan

by Muratbay Mambetaliyev, Sanat Kilibayev, Marzhan Kenzhebaeva, Nuraiym Sarsenkulova, Shalkar Tabys, Aisulu Valiyeva, Dias Muzarap, Moldir Tuyskanova, Balzhan Myrzakhmetova, Nurkuisa Rametov, Aizhamal Sarbassova, Ryspek Nurgaziev, Aslan Kerimbayev, Shawn Babiuk and Kuandyk Zhugunissov

Vaccines 2024, 12(6), 685; https://doi.org/10.3390/vaccines12060685 - 19 Jun 2024

Cited by 1 | Viewed by 1161

Abstract

An outbreak of camelpox occurred in the Mangistau region of Kazakhstan in 2019. To control the outbreak of camelpox and to prevent its further spread to other regions, camels were vaccinated using live and inactivated camelpox vaccines produced in Kazakhstan. To evaluate the [...] Read more.

An outbreak of camelpox occurred in the Mangistau region of Kazakhstan in 2019. To control the outbreak of camelpox and to prevent its further spread to other regions, camels were vaccinated using live and inactivated camelpox vaccines produced in Kazakhstan. To evaluate the efficacy of these camelpox vaccines in the field, vaccine trials used 172 camels on camel farms in the Beineu district. Of these, 132 camels were vaccinated using a live attenuated camelpox vaccine and 40 camels were vaccinated using an inactivated vaccine to observe immunogenicity and safety. The live vaccine was inoculated into camels by scarification at a dose of 5 × 10⁴ EID₅₀, and the inactivated vaccine was injected intramuscularly at 5 mL twice, with an interval of 35 days. During the safety evaluation, camels administered either vaccine displayed no clinical signs of illness or any adverse effects. Post-vaccination seroconversion demonstrated that the live attenuated vaccine started to elicit antibody responses in some animals as early as day seven, while, by day 28, 99% of vaccinated camels responded. For camels immunized with the inactivated vaccine, seroconversion began on day 21 at low titers ranging from 1:2 to 1:4. Ninety days post vaccination, 77% of the camels demonstrated an immune response that was up to a titer of 1:16. The antibody response waned six months post vaccination in camels vaccinated with two types of vaccine. Nonetheless, both vaccines were 100% effective at preventing clinical disease in vaccinated camels during the camelpox outbreak. All unvaccinated camels became ill, with manifestations of clinical signs characteristic of camelpox. Following these successful field trials in Kazakhstan, a vaccination program for camels, to control camelpox using the domestically produced live attenuated camelpox vaccine, has started. Full article

(This article belongs to the Special Issue Animal Virus Infection, Immunity and Vaccines)

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15 pages, 2848 KiB

Open AccessArticle

SARS-CoV-2-Specific Immune Cytokine Profiles to mRNA, Viral Vector and Protein-Based Vaccines in Patients with Multiple Sclerosis: Beyond Interferon Gamma

by Georges Katoul Al Rahbani, Christina Woopen, Marie Dunsche, Undine Proschmann, Tjalf Ziemssen and Katja Akgün

Vaccines 2024, 12(6), 684; https://doi.org/10.3390/vaccines12060684 - 19 Jun 2024

Viewed by 1554

Abstract

Disease-modifying therapies (DMTs) impact the cellular immune response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (pwMS). In this study, we aim to elucidate the characteristics of the involved antigen-specific T cells via the measurement of [...] Read more.

Disease-modifying therapies (DMTs) impact the cellular immune response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (pwMS). In this study, we aim to elucidate the characteristics of the involved antigen-specific T cells via the measurement of broad cytokine profiles in pwMS on various DMTs. We examined SARS-CoV-2-specific T cell responses in whole blood cultures characterized by the release of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-13, IL-17A, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α), as well as antibodies (AB) targeting the SARS-CoV-2 spike protein in pwMS following either two or three doses of mRNA or viral vector vaccines (VVV). For mRNA vaccination non-responders, the NVX-CoV2373 protein-based vaccine was administered, and immune responses were evaluated. Our findings indicate that immune responses to SARS-CoV-2 vaccines in pwMS are skewed towards a Th1 phenotype, characterized by IL-2 and IFN-γ. Additionally, a Th2 response characterized by IL-5, and to a lesser extent IL-4, IL-10, and IL-13, is observed. Therefore, the measurement of IL-2 and IL-5 levels could complement traditional IFN-γ assays to more comprehensively characterize the cellular responses to SARS-CoV-2 vaccines. Our results provide a comprehensive cytokine profile for pwMS receiving different DMTs and offer valuable insights for designing vaccination strategies in this patient population. Full article

(This article belongs to the Special Issue Interferon Responses after Vaccine Administration)

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17 pages, 2792 KiB

Open AccessArticle

Immunogenicity, Safety, and Immune Persistence of One Dose of SARS-CoV-2 Recombinant Adenovirus Type-5 Vectored Vaccine in Children and Adolescents Aged 6–17 Years: An Immunobridging Trial

by Xu Han, Mingwei Wei, Xiuyu Zheng, Peng Wan, Jie Tang, Lu Zhang, Shupeng Zhang, Hanchi Zhou, Jiayu Lu, Li Zhou, Yawen Zhu, Jingxin Li and Fengcai Zhu

Vaccines 2024, 12(6), 683; https://doi.org/10.3390/vaccines12060683 - 19 Jun 2024

Viewed by 882

Abstract

Background: Though children infected by SARS-CoV-2 generally experience milder symptoms compared to adults, severe cases can occur. Additionally, children can transmit the virus to others. Therefore, the availability of safe and effective COVID-19 vaccines for children and adolescents is crucial. Method: A single-center, [...] Read more.

Background: Though children infected by SARS-CoV-2 generally experience milder symptoms compared to adults, severe cases can occur. Additionally, children can transmit the virus to others. Therefore, the availability of safe and effective COVID-19 vaccines for children and adolescents is crucial. Method: A single-center, randomized, double-blind clinical trial was conducted in Funing County, Yancheng City, Jiangsu Province, China. Healthy children and adolescents were divided into two subgroups (6–12 years old or 13–17 years old) and randomly assigned to one of three groups to receive one dose of Ad5-nCoV (3 × 10¹⁰ vp/dose). Another group, aged 18–59, received one dose of Ad5-nCoV (5 × 10¹⁰ vp/dose) as the control group. At 28, 90, 180, and 360 days post-vaccination, we measured the geometric mean titer (GMT)/concentration (GMC) of neutralizing and binding antibodies against the prototype SARS-CoV-2 strain, as well as serum antibody levels against the BA.4/5 variant. We also evaluated the incidence of adverse events within 28 days post-vaccination. Results: A total of 2413 individuals were screened from 3 June 2021 to 25 July 2021, of whom 2021 eligible participants were enrolled, including 1009 aged 6~17 years in the children and adolescent group and 1012 aged 18–59 years in the adults group. The GMT of anti-wild SARS-CoV-2 neutralizing antibodies was 18.6 (95% CI, 16.6–20.9) in children and adolescents and 13.2 (95% CI, 11.6–15.0) in adults on day 28. The incidence of solicited adverse reactions between the adult group (49.4% [124/251]) and the children and adolescent group (46.3% [156/337]) was not statistically significant. The neutralizing antibody levels decreased by a factor of 3.29 from day 28 to day 360 post-vaccination. Conclusions: A single dose of Ad5-nCoV at 3 × 10¹⁰ virus particles/dose is safe in children and adolescents, and it elicited significant immune response, which was not only non-inferior but also superior to that in adults aged 18–59 years. Full article

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15 pages, 900 KiB

Open AccessArticle

Hybrid Immunity and the Incidence of SARS-CoV-2 Reinfections during the Omicron Era in Frontline Healthcare Workers

by Carmen-Daniela Chivu, Maria-Dorina Crăciun, Daniela Pițigoi, Victoria Aramă, Monica Luminița Luminos, Gheorghiță Jugulete, Viorela Gabriela Nițescu, Andreea Lescaie, Cătălin Gabriel Apostolescu and Adrian Streinu Cercel

Vaccines 2024, 12(6), 682; https://doi.org/10.3390/vaccines12060682 - 19 Jun 2024

Viewed by 1027

Abstract

During the coronavirus disease (COVID-19) pandemic healthcare workers (HCWs) acquired immunity by vaccination or exposure to multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our study is a comparative analysis between subgroups of HCWs constructed based on the number of SARS-CoV-2 [...] Read more.

During the coronavirus disease (COVID-19) pandemic healthcare workers (HCWs) acquired immunity by vaccination or exposure to multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our study is a comparative analysis between subgroups of HCWs constructed based on the number of SARS-CoV-2 infections, vaccination, and the dominant variant of SARS-CoV-2 in the population. We collected and analyzed data using the χ² test and density incidence of reinfections in Microsoft Excel for Mac, Version 16.84, and MedCalc^®, 22.026. Of the 829 HCWs, 70.1% (581) had only one SARS-CoV-2 infection and 29.9% (248) had two infections. Of the subjects with two infections, 77.4% (192) worked in high-risk departments and 93.2% (231) of the second infections were registered during Omicron dominance. The density incidence of reinfections was higher in HCWs vaccinated with the primary schedule than those vaccinated with the first booster, and the incidence ratio was 2.8 (95% CI: 1.2; 6.7). The probability of reinfection was five times lower (95% CI: 2.9; 9.2) in HCWs vaccinated with the primary schedule if the first infection was acquired during Omicron dominance. The subjects vaccinated with the first booster had a density incidence of reinfection three times lower (95% CI: 1.9; 5.8) if the first infection was during Omicron. The incidence ratio in subgroups constructed based on characteristics such as gender, age group, job category, and department also registered significant differences in density incidence. The history of SARS-CoV-2 infection by variant is important when interpreting and understanding public health data and the results of studies related to vaccine efficacy for hybrid immunity subgroup populations. Full article

(This article belongs to the Special Issue Influence of Natural and/or Vaccine Immunity on the Dynamics of SARS-CoV-2)

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12 pages, 3067 KiB

Open AccessArticle

Water-Soluble and Freezable Aluminum Salt Vaccine Adjuvant

by Erwin G. Abucayon, Ilya Belikow-Crovetto, Elizabeth Hussin, Jiae Kim, Gary R. Matyas, Mangala Rao and Carl R. Alving

Vaccines 2024, 12(6), 681; https://doi.org/10.3390/vaccines12060681 - 19 Jun 2024

Viewed by 1259

Abstract

Particulate aluminum salts have long occupied a central place worldwide as inexpensive immunostimulatory adjuvants that enable induction of protective immunity for vaccines. Despite their huge benefits and safety, the particulate structures of aluminum salts require transportation and storage at temperatures between 2 °C [...] Read more.

Particulate aluminum salts have long occupied a central place worldwide as inexpensive immunostimulatory adjuvants that enable induction of protective immunity for vaccines. Despite their huge benefits and safety, the particulate structures of aluminum salts require transportation and storage at temperatures between 2 °C and 8 °C, and they all have exquisite sensitivity to damage caused by freezing. Here, we propose to solve the critical freezing vulnerability of particulate aluminum salt adjuvants by introducing soluble aluminum salts as adjuvants. The solubility properties of fresh and frozen aluminum chloride and aluminum triacetate, each buffered optimally with sodium acetate, were demonstrated with visual observations and with UV–vis scattering analyses. Two proteins, A244 gp120 and CRM₁₉₇, adjuvanted either with soluble aluminum chloride or soluble aluminum triacetate, each buffered by sodium acetate at pH 6.5–7.4, elicited murine immune responses that were equivalent to those obtained with Alhydrogel^®, a commercial particulate aluminum hydroxide adjuvant. The discovery of the adjuvanticity of soluble aluminum salts might require the creation of a new adjuvant mechanism for aluminum salts in general. However, soluble aluminum salts might provide a practical substitute for particulate aluminum salts as vaccine adjuvants, thereby avoiding the risk of inactivation of vaccines due to accidental freezing of aluminum salt particles. Full article

(This article belongs to the Section Vaccine Adjuvants)

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12 pages, 2373 KiB

Open AccessArticle

Evaluation of Formalin-Inactivated Vaccine Efficacy against Red Seabream Iridovirus (RSIV) in Laboratory and Field Conditions

by Joon-Gyu Min, Guk-Hyun Kim, Chong-Han Kim, Woo-Ju Kwon, Hyun-Do Jeong and Kwang-Il Kim

Vaccines 2024, 12(6), 680; https://doi.org/10.3390/vaccines12060680 - 19 Jun 2024

Viewed by 879

Abstract

Red seabream iridovirus (RSIV) is a major cause of marine fish mortality in Korea, with no effective vaccine available since its first occurrence in the 1990s. This study evaluated the efficacy of a formalin-killed vaccine against RSIV in rock bream under laboratory and [...] Read more.

Red seabream iridovirus (RSIV) is a major cause of marine fish mortality in Korea, with no effective vaccine available since its first occurrence in the 1990s. This study evaluated the efficacy of a formalin-killed vaccine against RSIV in rock bream under laboratory and field conditions. For the field trial, a total of 103,200 rock bream from two commercial marine cage-cultured farms in Southern Korea were vaccinated. Farm A vaccinated 31,100 fish in July 2020 and monitored them for 18 weeks, while farm B vaccinated 30,700 fish in August 2020 and monitored them for 12 weeks. At farm A, where there was no RSIV infection, the vaccine efficacy was assessed in the lab, showing a relative percentage of survival (RPS) ranging from 40% to 80%. At farm B, where natural RSIV infections occurred, cumulative mortality rates were 36.43% in the vaccinated group and 80.32% in the control group, resulting in an RPS of 54.67%. The RSIV-infectious status and neutralizing antibody titers in serum mirrored the cumulative mortality results. This study demonstrates that the formalin-killed vaccine effectively prevents RSIV in cage-cultured rock bream under both laboratory and field conditions. Full article

(This article belongs to the Special Issue Fish Disease Occurrence and Immune Prevention and Control)

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16 pages, 3322 KiB

Open AccessArticle

Assessing Predictive Value of SARS-CoV-2 Epitope-Specific CD8⁺ T-Cell Response in Patients with Severe Symptoms

by Cristina Martín-Martín, Estefanía Salgado del Riego, Jose R. Vidal Castiñeira, Maria Soledad Zapico-Gonzalez, Mercedes Rodríguez-Pérez, Viviana Corte-Iglesias, Maria Laura Saiz, Paula Diaz-Bulnes, Dolores Escudero, Beatriz Suárez-Alvarez and Carlos López-Larrea

Vaccines 2024, 12(6), 679; https://doi.org/10.3390/vaccines12060679 - 18 Jun 2024

Viewed by 1329

Abstract

Specific T cell responses against SARS-CoV-2 provided an overview of acquired immunity during the pandemic. Anti-SARS-CoV-2 immunity determines the severity of acute illness, but also might be related to the possible persistence of symptoms (long COVID). We retrospectively analyzed ex vivo longitudinal CD8 [...] Read more.

Specific T cell responses against SARS-CoV-2 provided an overview of acquired immunity during the pandemic. Anti-SARS-CoV-2 immunity determines the severity of acute illness, but also might be related to the possible persistence of symptoms (long COVID). We retrospectively analyzed ex vivo longitudinal CD8⁺ T cell responses in 26 COVID-19 patients diagnosed with severe disease, initially (1 month) and long-term (10 months), and in a cohort of 32 vaccinated healthcare workers without previous SARS-CoV-2 infection. We used peptide-human leukocyte antigen (pHLA) dextramers recognizing 26 SARS-CoV-2-derived epitopes of viral and other non-structural proteins. Most patients responded to at least one of the peptides studied, mainly derived from non-structural ORF1ab proteins. After 10 months follow-up, CD8⁺ T cell responses were maintained at long term and reaction against certain epitopes (A*01:01-ORF1ab1637) was still detected and functional, showing a memory-like phenotype (CD127+ PD-1+). The total number of SARS-CoV-2-specific CD8⁺ T cells was significantly associated with protection against long COVID in these patients. Compared with vaccination, infected patients showed a less effective immune response to spike protein-derived peptides restricted by HLA. So, the A*01:01-S865 and A*24:02-S1208 dextramers were only recognized in vaccinated individuals. We conclude that initial SARS-CoV-2-specific CD8⁺ T cell response could be used as a marker to understand the evolution of severe disease and post-acute sequelae after SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue Population Immunity and Persistence to SARS-CoV-2 Induced by Infection and Vaccination, Protection against New Infections and Implication for Further Vaccination)

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13 pages, 685 KiB

Open AccessArticle

Real-World Assessment of Recommended COVID-19 Vaccination Waiting Period after Chemotherapy

by Kai-Wen Cheng, Chi-Hua Yen, Renin Chang, James Cheng-Chung Wei and Shiow-Ing Wang

Vaccines 2024, 12(6), 678; https://doi.org/10.3390/vaccines12060678 - 18 Jun 2024

Viewed by 1170

Abstract

There is a knowledge gap concerning the proper timing for COVID-19 vaccination in cancer patients undergoing chemotherapy. We aimed to evaluate the suitability of the guidelines that recommend waiting at least three months after undergoing chemotherapy before receiving a COVID-19 vaccine. This retrospective [...] Read more.

There is a knowledge gap concerning the proper timing for COVID-19 vaccination in cancer patients undergoing chemotherapy. We aimed to evaluate the suitability of the guidelines that recommend waiting at least three months after undergoing chemotherapy before receiving a COVID-19 vaccine. This retrospective cohort study used aggregated data from the TriNetX US Collaboratory network. Participants were grouped into two groups based on the interval between chemotherapy and vaccination. The primary outcome assessed was infection risks, including COVID-19; skin, intra-abdominal, and urinary tract infections; pneumonia; and sepsis. Secondary measures included healthcare utilization and all causes of mortality. Kaplan–Meier analysis and the Cox proportional hazard model were used to calculate the cumulative incidence and hazard ratio (HR) and 95% confidence intervals for the outcomes. The proportional hazard assumption was tested with the generalized Schoenfeld approach. Four subgroup analyses (cancer type, vaccine brand, sex, age) were conducted. Sensitivity analyses were performed to account for competing risks and explore three distinct time intervals. Patients receiving a vaccine within three months after chemotherapy had a higher risk of COVID-19 infection (HR: 1.428, 95% CI: 1.035–1.970), urinary tract infection (HR: 1.477, 95% CI: 1.083–2.014), and sepsis (HR: 1.854, 95% CI: 1.091–3.152) compared to those who adhered to the recommendations. Hospital inpatient service utilization risk was also significantly elevated for the within three months group (HR: 1.692, 95% CI: 1.354–2.115). Adhering to a three-month post-chemotherapy waiting period reduces infection and healthcare utilization risks for cancer patients receiving a COVID-19 vaccine. Full article

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17 pages, 3627 KiB

Open AccessReview

Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas

by Kawaljit Kaur, Jashan Sanghu, Sanaz Memarzadeh and Anahid Jewett

Vaccines 2024, 12(6), 677; https://doi.org/10.3390/vaccines12060677 - 18 Jun 2024

Viewed by 1610

Abstract

High-grade serous ovarian cancers (HGSOCs) likely consist of poorly differentiated stem-like cells (PDSLCs) and differentiated tumor cells. Conventional therapeutics are incapable of completely eradicating PDSLCs, contributing to disease progression and tumor relapse. Primary NK cells are known to effectively lyse PDSLCs, but they [...] Read more.

High-grade serous ovarian cancers (HGSOCs) likely consist of poorly differentiated stem-like cells (PDSLCs) and differentiated tumor cells. Conventional therapeutics are incapable of completely eradicating PDSLCs, contributing to disease progression and tumor relapse. Primary NK cells are known to effectively lyse PDSLCs, but they exhibit low or minimal cytotoxic potential against well-differentiated tumors. We have introduced and discussed the characteristics of super-charged NK (sNK) cells in this review. sNK cells, in comparison to primary NK cells, exhibit a significantly higher capability for the direct killing of both PDSLCs and well-differentiated tumors. In addition, sNK cells secrete significantly higher levels of cytokines, especially those known to induce the differentiation of tumors. In addition, we propose that a combination of sNK and chemotherapy could be one of the most effective strategies to eliminate the heterogeneous population of ovarian tumors; sNK cells can lyse both PDSLCs and well-differentiated tumors, induce the differentiation of PDSLCs, and could be used in combination with chemotherapy to target both well-differentiated and NK-induced differentiated tumors. Full article

(This article belongs to the Section Cancer Vaccines and Immunotherapy)

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25 pages, 3860 KiB

Open AccessArticle

S2 Peptide-Conjugated SARS-CoV-2 Virus-like Particles Provide Broad Protection against SARS-CoV-2 Variants of Concern

by Chang-Kyu Heo, Won-Hee Lim, Ki-Beom Moon, Jihyun Yang, Sang Jick Kim, Hyun-Soon Kim, Doo-Jin Kim and Eun-Wie Cho

Vaccines 2024, 12(6), 676; https://doi.org/10.3390/vaccines12060676 - 18 Jun 2024

Viewed by 1363

Abstract

Approved COVID-19 vaccines primarily induce neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, the emergence of variants of concern with RBD mutations poses challenges to vaccine efficacy. This study aimed to design a next-generation vaccine that provides [...] Read more.

Approved COVID-19 vaccines primarily induce neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, the emergence of variants of concern with RBD mutations poses challenges to vaccine efficacy. This study aimed to design a next-generation vaccine that provides broader protection against diverse coronaviruses, focusing on glycan-free S2 peptides as vaccine candidates to overcome the low immunogenicity of the S2 domain due to the N-linked glycans on the S antigen stalk, which can mask S2 antibody responses. Glycan-free S2 peptides were synthesized and attached to SARS-CoV-2 virus-like particles (VLPs) lacking the S antigen. Humoral and cellular immune responses were analyzed after the second booster immunization in BALB/c mice. Enzyme-linked immunosorbent assay revealed the reactivity of sera against SARS-CoV-2 variants, and pseudovirus neutralization assay confirmed neutralizing activities. Among the S2 peptide-conjugated VLPs, the S2.3 (N1135-K1157) and S2.5 (A1174-L1193) peptide–VLP conjugates effectively induced S2-specific serum immunoglobulins. These antisera showed high reactivity against SARS-CoV-2 variant S proteins and effectively inhibited pseudoviral infections. S2 peptide-conjugated VLPs activated SARS-CoV-2 VLP-specific T-cells. The SARS-CoV-2 vaccine incorporating conserved S2 peptides and CoV-2 VLPs shows promise as a universal vaccine capable of generating neutralizing antibodies and T-cell responses against SARS-CoV-2 variants. Full article

(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies)

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32 pages, 2118 KiB

Open AccessReview

An Overview of the Strategies to Boost SARS-CoV-2-Specific Immunity in People with Inborn Errors of Immunity

by Emma Chang-Rabley, Menno C. van Zelm, Emily E. Ricotta and Emily S. J. Edwards

Vaccines 2024, 12(6), 675; https://doi.org/10.3390/vaccines12060675 - 18 Jun 2024

Viewed by 1451

Abstract

The SARS-CoV-2 pandemic has heightened concerns about immunological protection, especially for individuals with inborn errors of immunity (IEI). While COVID-19 vaccines elicit strong immune responses in healthy individuals, their effectiveness in IEI patients remains unclear, particularly against new viral variants and vaccine formulations. [...] Read more.

The SARS-CoV-2 pandemic has heightened concerns about immunological protection, especially for individuals with inborn errors of immunity (IEI). While COVID-19 vaccines elicit strong immune responses in healthy individuals, their effectiveness in IEI patients remains unclear, particularly against new viral variants and vaccine formulations. This uncertainty has led to anxiety, prolonged self-isolation, and repeated vaccinations with uncertain benefits among IEI patients. Despite some level of immune response from vaccination, the definition of protective immunity in IEI individuals is still unknown. Given their susceptibility to severe COVID-19, strategies such as immunoglobulin replacement therapy (IgRT) and monoclonal antibodies have been employed to provide passive immunity, and protection against both current and emerging variants. This review examines the efficacy of COVID-19 vaccines and antibody-based therapies in IEI patients, their capacity to recognize viral variants, and the necessary advances required for the ongoing protection of people with IEIs. Full article

(This article belongs to the Special Issue Influence of Natural and/or Vaccine Immunity on the Dynamics of SARS-CoV-2)

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10 pages, 1280 KiB

Open AccessArticle

Glycoprotein-Specific Polyclonal Antibodies Targeting Machupo Virus Protect Guinea Pigs against Lethal Infection

by Joseph W. Golden, Steven A. Kwilas and Jay W. Hooper

Vaccines 2024, 12(6), 674; https://doi.org/10.3390/vaccines12060674 - 18 Jun 2024

Viewed by 1072

Abstract

Convalescent plasma has been shown to be effective at protecting humans against severe diseases caused by New World (NW) arenaviruses, including Junin virus (JUNV) and Machupo virus (MACV). This plasma contains antibodies against the full complement of structural proteins including the nucleocapsid and [...] Read more.

Convalescent plasma has been shown to be effective at protecting humans against severe diseases caused by New World (NW) arenaviruses, including Junin virus (JUNV) and Machupo virus (MACV). This plasma contains antibodies against the full complement of structural proteins including the nucleocapsid and envelope glycoproteins (GPcs) consisting of GP1 and GP2. To gain insights into the protective and cross-protective properties of anti-GPc-specific polyclonal antibodies, we evaluated the ability of a DNA vaccine-produced anti-GPc rabbit antisera targeting MACV strain Carvallo to provide heterologous protection against another MACV strain termed Chicava in the Hartley guinea pig model. The neutralizing activity of the rabbit antisera against the heterologous MACV strains Chicava and Mallale was found to be 54-fold and 23-fold lower, respectively, compared to the titer against the homologous MACV strain Carvallo in the PRNT50 assay. Despite lower neutralizing activity against the strain Chicava, the rabbit antisera protected 100% of the guinea pigs from this strain when administered up to four days post-infection, whereas all the control animals succumbed to the disease. Using vesicular stomatitis virus (VSV) particles pseudotyped with MACV GPc, we identified a single amino acid difference at position 122 between the strains Chicava and Carvallo GPc that significantly influenced the neutralization activity of the rabbit antisera. These findings indicate that polyclonal antibodies targeting the MACV glycoproteins can protect against lethal infection in a post-challenge setting. These data will help guide future antibody-based therapeutics development against NW arenaviruses. Full article

(This article belongs to the Special Issue Immunotherapy and Vaccine Development for Viral Diseases)

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15 pages, 1060 KiB

Open AccessArticle

Safety Assessment of Concurrent Vaccination with the HPV Vaccine and the COVID-19 Vaccine in Fujian Province, China: A Retrospective Study

by Yan Zhang, Yuhang Zhang, Binhua Dong, Wenyu Lin, Yuxuan Huang, Kelvin Stefan Osafo, Xite Lin, Tingting Jiang, Yu Zhang, Huachun Zou and Pengming Sun

Vaccines 2024, 12(6), 673; https://doi.org/10.3390/vaccines12060673 - 18 Jun 2024

Viewed by 1468

Abstract

During acute respiratory infections, women may concurrently receive human papillomavirus (HPV) and respiratory vaccines, as observed during the coronavirus disease 2019 (COVID-19) pandemic in China. However, few studies have assessed the safety of such concurrent administration, which could impact HPV vaccination schedules. This [...] Read more.

During acute respiratory infections, women may concurrently receive human papillomavirus (HPV) and respiratory vaccines, as observed during the coronavirus disease 2019 (COVID-19) pandemic in China. However, few studies have assessed the safety of such concurrent administration, which could impact HPV vaccination schedules. This study analyzes the safety and optimal sequence of concurrent HPV and COVID-19 vaccinations. For this purpose, we surveyed women with both vaccines from January to October 2023 in Fujian Province, China. During this process, we collected vaccination history and adverse event (AE) data via telephone or interviews. Participants were grouped as Before, Concurrent, or After based on their vaccination sequence. A Chi-squared test, exact Fisher tests, and logistic regression were used to analyze the incidence of AEs and factors influencing vaccine safety. Overall, 1416 eligible participants were included. Although overall AE risk with the HPV vaccine was unaffected by vaccination sequence, individual AEs varied statistically between groups, including pain at the vaccination site (p < 0.001) and prolonged menstruation duration (p = 0.003). Based on the results, the optimal sequence would be to receive the HPV vaccine after the COVID-19 vaccine (After group). This insight may guide future emergency vaccination sequences for HPV and other respiratory infectious diseases. Full article

(This article belongs to the Section Human Papillomavirus Vaccines)

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20 pages, 1200 KiB

Open AccessArticle

Effectiveness and Safety of the COVID-19 Vaccine in Patients with Rheumatoid Arthritis in a Real-World Setting

by María Torres-Rufas, Esther F. Vicente-Rabaneda, Laura Cardeñoso, Ainhoa Gutierrez, David A. Bong, Cristina Valero-Martínez, José M. Serra López-Matencio, Rosario García-Vicuña, Miguel A. González-Gay, Isidoro González-Álvaro and Santos Castañeda

Vaccines 2024, 12(6), 672; https://doi.org/10.3390/vaccines12060672 - 18 Jun 2024

Viewed by 1281

Abstract

Novel mechanisms of COVID-19 vaccines raised concern about their potential immunogenicity in patients with rheumatoid arthritis (RA) undergoing immunomodulatory treatments. We designed a retrospective single-center study to investigate their effectiveness and safety in this population, analyzing data from the first vaccination program (December [...] Read more.

Novel mechanisms of COVID-19 vaccines raised concern about their potential immunogenicity in patients with rheumatoid arthritis (RA) undergoing immunomodulatory treatments. We designed a retrospective single-center study to investigate their effectiveness and safety in this population, analyzing data from the first vaccination program (December 2020–October 2021). Inclusion criteria were availability of post-vaccination serology and a minimum subsequent follow-up of 6 months. Binding antibody units (BAU/mL) ≥ 7.1 defined an adequate serological response. Post-vaccine COVID-19 incidence and its timing since vaccination, adverse events (AEs), and RA flares were recorded. Adjusted logistic and linear multivariate regression analyses were carried out to identify factors associated with vaccine response. We included 118 patients (87.2% women, age 65.4 ± 11.6 years, evolution 12.0 ± 9.6 years), of whom 95.8% had a complete vaccination schedule. Adequate humoral immunogenicity was achieved in 88.1% of patients and was associated with previous COVID-19 and mRNA vaccines, whereas smoking, aCCP, age, and DMARDs exerted a negative impact. Post-vaccine COVID-19 occurred in 18.6% of patients, a median of 6.5 months after vaccination. Vaccine AE (19.5%) and RA flares (1.7%) were mostly mild and inversely associated with age. Our results suggest that COVID-19 vaccines induce adequate humoral immunogenicity, with an acceptable safety profile in RA patients. Full article

(This article belongs to the Special Issue 2nd Edition: Safety and Autoimmune Response to SARS-CoV-2 Vaccination)

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25 pages, 1633 KiB

Open AccessArticle

Human Papillomavirus Perceptions, Vaccine Uptake, and Sexual Risk Factors in Students Attending a Large Public Midwestern University

by JaNiese E. Jensen, Linder H. Wendt, Joseph C. Spring and Jay Brooks Jackson

Vaccines 2024, 12(6), 671; https://doi.org/10.3390/vaccines12060671 - 17 Jun 2024

Viewed by 1111

Abstract

Background: It was to understand HPV vaccination patterns, uptake, perceptions, and sexual risk factors in students at a Midwest public university. Participants: Students were enrolled during the spring 2024 semester at the University of Iowa. Methods: A survey was developed and emailed to [...] Read more.

Background: It was to understand HPV vaccination patterns, uptake, perceptions, and sexual risk factors in students at a Midwest public university. Participants: Students were enrolled during the spring 2024 semester at the University of Iowa. Methods: A survey was developed and emailed to 28,095 students asking demographic, general and sexual health, and HPV-related questions. Results: The response rate was 4.9%, with 76% females and a median age of 22. The HPV vaccine uptake was 82%, with 88% recommending the vaccine. Parental preference was the main reason for being unvaccinated. The median age of sexual debut was 17 years, with a median of 2 sexual partners. Vaccination was associated with female, health science, sexually active, and COVID-19/influenza vaccinated students. Conclusions: HPV vaccine uptake at University of Iowa students is higher than the national and Iowa averages. Increased education regarding HPV vaccination is still needed, particularly in males, those not having sex, and those not receiving other vaccines. Full article

(This article belongs to the Special Issue Prevention of Human Papillomavirus and Vaccines Strategies)

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18 pages, 765 KiB

Open AccessReview

mRNA Technology and Mucosal Immunization

by Antonio Toniolo, Giuseppe Maccari and Giovanni Camussi

Vaccines 2024, 12(6), 670; https://doi.org/10.3390/vaccines12060670 - 17 Jun 2024

Viewed by 1441

Abstract

Current mRNA vaccines are mainly administered via intramuscular injection, which induces good systemic immunity but limited mucosal immunity. Achieving mucosal immunity through mRNA vaccination could diminish pathogen replication at the entry site and reduce interhuman transmission. However, delivering mRNA vaccines to mucosae faces [...] Read more.

Current mRNA vaccines are mainly administered via intramuscular injection, which induces good systemic immunity but limited mucosal immunity. Achieving mucosal immunity through mRNA vaccination could diminish pathogen replication at the entry site and reduce interhuman transmission. However, delivering mRNA vaccines to mucosae faces challenges like mRNA degradation, poor entry into cells, and reactogenicity. Encapsulating mRNA in extracellular vesicles may protect the mRNA and reduce reactogenicity, making mucosal mRNA vaccines possible. Plant-derived extracellular vesicles from edible fruits have been investigated as mRNA carriers. Studies in animals show that mRNA vehiculated in orange-derived extracellular vesicles can elicit both systemic and mucosal immune responses when administered by the oral, nasal, or intramuscular routes. Once lyophilized, these products show remarkable stability. The optimization of mRNA to improve translation efficiency, immunogenicity, reactogenicity, and stability can be obtained through adjustments of the 5′cap region, poly-A tail, codons selection, and the use of nucleoside analogues. Recent studies have also proposed self-amplifying RNA vaccines containing an RNA polymerase as well as circular mRNA constructs. Data from parenterally primed animals demonstrate the efficacy of nasal immunization with non-adjuvanted protein, and studies in humans indicate that the combination of a parenteral vaccine with the natural exposure of mucosae to the same antigen provides protection and reduces transmission. Hence, mucosal mRNA vaccination would be beneficial at least in organisms pre-treated with parenteral vaccines. This practice could have wide applications for the treatment of infectious diseases. Full article

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