Vaccines, Volume 11, Issue 3 (March 2023) – 221 articles

This study aims to investigate the causes of COVID-19 vaccine hesitancy among the Chinese population. The LDA model and content analysis were used to analyze the content of COVID-19 vaccine hesitancy expressed by the Chinese on Weibo from 2020 to 2022, the leading causes of vaccine hesitancy, and the changes in the reasons for vaccine hesitancy over time. The study found that when the Chinese expressed vaccine hesitancy, it usually involved themes such as information access (18.59%), vaccination services (13.91%), and physical illness (13.24%), and topics such as vaccination process (6.83%), allergic diseases (6.59%), and international news (6.43%). Constraints (35.48%), confidence (17.94%), and calculation (15.99%) are the leading causes of vaccine hesitancy on Weibo. These findings provide a comprehensive picture of how the Chinese express vaccine hesitancy in social media and the reasons and changes for vaccine hesitancy, which can help inspire public health experts, health organizations, or governments in various countries to improve the phenomenon of vaccine hesitancy. Full article

The major concern with COVID-19 therapeutic monoclonal antibodies is the loss of efficacy against continuously emerging variants of SARS-CoV-2. To predict antibody efficacy against future Omicron subvariants, we conducted deep mutational scanning (DMS) encompassing all single mutations of the receptor-binding domain of the BA.2 strain utilizing an inverted infection assay with an ACE2-harboring virus and library spike-expressing cells. In the case of bebtelovimab, which preserves neutralization activity against BA.2 and BA.5, a broad range of amino acid substitutions at K444, V445, and G446, and some substitutions at P499 and T500, were indicated to achieve the antibody escape. Among subvariants with current rises in case numbers, BA2.75 with G446S partially evaded neutralization by bebtelovimab, while complete evasion was observed in XBB with V445P and BQ.1 with K444T. This is consistent with the DMS results against BA.2, highlighting the potential of DMS as a predictive tool for antibody escape. Full article

Hepatitis E Virus (HEV) is a major cause of acute and chronic hepatitis. The severity of HEV infection increases manyfold in pregnant women and immunocompromised patients. Despite the extensive research on HEV in the last few decades, there is no widely available vaccine yet. In the current study, immunoinformatic analyses were applied to predict a multi-epitope vaccine candidate against HEV. From the ORF2 region, 41 conserved and immunogenic epitopes were prioritized. These epitopes were further analyzed for their probable antigenic and non-allergenic combinations with several linkers. The stability of the vaccine construct was confirmed by molecular dynamic simulations. The vaccine construct is potentially antigenic and docking analysis revealed stable interactions with TLR3. These results suggest that the proposed vaccine can efficiently stimulate both cellular and humoral immune responses. However, further studies are needed to determine the immunogenicity of the vaccine construct. Full article

The sentiment analysis of social media for predicting behavior during a pandemic is seminal in nature. As an applied contribution, we present sentiment-based regression models for predicting the United States COVID-19 first dose, second dose, and booster daily inoculations from 1 June 2021 to 31 March 2022. The models merge independent variables representing fear of the virus and vaccine hesitancy. Large correlations exceeding 77% and 84% for the first-dose and booster-dose models inspire confidence in the merger of the independent variables. Death count as a traditional measure of fear is a lagging indicator of inoculations, while Twitter-positive and -negative tweets are strong predictors of inoculations. Thus, the use of sentiment analysis for predicting inoculations is strongly supported with administrative events being catalysts for tweets. Non-inclusion in the second-dose regression model of data occurring before the 1 June 2021 timeframe appear to limit the second-dose model results—only achieving a moderate correlation exceeding 53%. Limiting tweet collection to geolocated tweets does not encompass the entire US Twitter population. Nonetheless, results from Kaiser Family Foundation (KFF) surveys appear to generally support the regression factors common to the first-dose and booster-dose regression models and their results. Full article

Newcastle disease virus (NDV) and avian metapneumovirus (aMPV) are among the most impactful pathogens affecting the turkey industry. Since turkeys are routinely immunized against both diseases, the hatchery administration of the combined respective live vaccines would offer remarkable practical advantages. However, the compatibility of NDV and aMPV vaccines has not yet been experimentally demonstrated in this species. To address this issue, an aMPV subtype B live vaccine was administered to day-old poults either alone or in combination with one of two different ND vaccines. The birds were then challenged with a virulent aMPV subtype B strain, clinical signs were recorded and aMPV and NDV vaccine replication and humoral immune response were assessed. All results supported the absence of any interference hampering protection against aMPV, with no significant differences in terms of clinical scoring. In addition, the mean aMPV vaccine viral titers and antibody titers measured in the dual vaccinated groups were comparable or even higher than in the group vaccinated solely against aMPV. Lastly, based on the NDV viral and antibody titers, the combined aMPV and NDV vaccination does not seem to interfere with protection against NDV, although further studies involving an actual ND challenge will be necessary to fully demonstrate this hypothesis. Full article

Live-attenuated Rift Valley fever (RVF) vaccines transiently replicate in the vaccinated host, thereby effectively initiating an innate and adaptive immune response. Rift Valley fever virus (RVFV)-specific neutralizing antibodies are considered the main correlate of protection. Vaccination with classical live-attenuated RVF vaccines during gestation in livestock has been associated with fetal malformations, stillbirths, and fetal demise. Facilitated by an increased understanding of the RVFV infection and replication cycle and availability of reverse genetics systems, novel rationally-designed live-attenuated candidate RVF vaccines with improved safety profiles have been developed. Several of these experimental vaccines are currently advancing beyond the proof-of-concept phase and are being evaluated for application in both animals and humans. We here provide perspectives on some of these next-generation live-attenuated RVF vaccines and highlight the opportunities and challenges of these approaches to improve global health. Full article

Following the rollout of a booster campaign to promote immunity against COVID-19 in China, this study aimed to assess booster hesitancy among adults who were fully vaccinated with primary doses across Zhejiang Province. Firstly, the modified 5C scale developed by a German research team was assessed for reliability and validity via a pre-survey in Zhejiang Province. Then, a 30-item questionnaire was established to conduct online and offline surveys during 10 November to 15 December 2021. Demographic characteristics and information on previous vaccination experience, vaccine type of primary doses, attitudes towards booster doses and awareness of SARS-CoV-2 infection were collected. Chi-square tests, pairwise comparison and multivariate logistic regression were performed in data analysis. In total, 4039 valid questionnaires were analyzed, with booster hesitancy of 14.81%. Dissatisfaction with previous vaccination experience of primary doses (ORs = 1.771~8.025), less confidence in COVID-19 vaccines (OR = 3.511, 95%CI: 2.874~4.310), younger age compared to the elderly aged 51–60 years old (2.382, 1.274~4.545), lower education level (ORs = 1.707~2.100), weaker awareness of social responsibility of prevention and control of COVID-19 (1.587, 1.353~1.859), inconvenience of booster vaccination (1.539, 1.302~1.821), complacency regarding vaccine efficacy as well as self-health status (1.224, 1.056~1.415) and excessive trade-offs before vaccination (1.184, 1.005~1.398) were positively associated with booster hesitancy. Therefore, intelligent means should be strengthened to optimize vaccination services. More influential experts and other significant figures should be supported to promote timely evidence-based information via various media platforms to reduce public hesitancy and increase booster uptake. Full article

As the COVID-19 pandemic erupted, attempts to contain the spread of the virus took two concurrent forms, including mobility restrictions (aka lockdowns) and the race to produce a vaccine. However, it is quite striking that, amidst both the lockdown and the race to produce a vaccine, the question of how COVID-19 survivors/patients coped with the disease has not received the degree of attention it deserved. To navigate this issue, we employed a sample consisting of 100 COVID-19 survivors; this paper explores the relationship between the biopsychosocial (BPS) impacts of COVID-19, death anxiety, and coping strategies. In this context, the mediating role of death anxiety is placed in the spotlight. The analysis reveals a significant positive association between the BPS impact of COVID-19 and death anxiety and a significant negative association between death anxiety and coping strategies among COVID-19 survivors. Thus, death anxiety mediates the relationship between the BPS impact and the coping strategies that COVID-19 survivors adopt. Given the general recognition of the validity of the BPS model in contemporary medical science and practice, a thorough examination of COVID-19 survivors and their experiences related to surviving is necessary to match the challenges of today, including the increased probability of pandemics. Full article

Vaccines are considered the best protective means against coronavirus infection. There is increasing interest in reporting the side effects of vaccines, especially for individuals younger than 18 years old. Accordingly, this analytical cohort study aims to report on the side effects of adult and young individuals who received vaccination within 24 h, 72 h, 5 days, and 1 week through the entire course of vaccination (ECoV). A validated online survey was used to collect information. In total, 1069 individuals were completely followed. Most individuals received the Pfizer vaccine (59.6%). Most individuals had received two doses (69.4%). Very strong and statistically significant associations with side effects (p < 0.05, Phi (Φ) > 0.25) throughout the ECoV were reported for the type of vaccine and female gender. Non-smokers reported weak statistically significant associations. Fatigue and localized pain were the most commonly reported side effect, with onset within 24 h and duration of less than 72 h. The prevalence of reported side effects was statistically significantly higher among young individuals (<18 years old) than among adults (X² (1) =7.6, p = 0.006. Phi φ = 0.11). Full article

Background: Patients with immune-mediated inflammatory diseases (IMIDs) treated with immunomodulatory therapy present an increased susceptibility to infections. Vaccination is a crucial element in the management of IMID patients; however, rates remain suboptimal. This study intended to clarify the adherence to prescribed vaccines. Materials and methods: This prospective cohort study included 262 consecutive adults with inflammatory bowel disease and rheumatological diseases who underwent an infectious diseases evaluation before initiating or switching immunosuppressive/biological therapy. Vaccine prescription and adherence were assessed during an infectious diseases (ID) consultation using a real-world multidisciplinary clinical project. Results: At baseline, less than 5% had all their vaccines up-to-date. More than 650 vaccines were prescribed to 250 (95.4%) patients. The most prescribed were pneumococcal and influenza vaccines, followed by hepatitis A and B vaccines. Adherence to each of the vaccines ranged from 69.1–87.3%. Complete adherence to vaccines occurred in 151 (60.4%) patients, while 190 (76%) got at least two-thirds of them. Twenty patients (8%) did not adhere to any of the vaccines. No significant differences were found in the adherence rates of patients with different sociodemographic and health-related determinants. Conclusions: ID physicians can play a role in the process of increasing vaccine prescription and adherence. However, more data on patients’ beliefs and vaccine hesitancy, along with mobilization of all health care professionals and adequate local interventions, shall be considered to improve vaccine adherence. Full article

Presence of a large foreign workforce and the annual gathering of people for pilgrimage from around the globe have significantly contributed to the emergence and diversity of respiratory viruses in Saudi Arabia. Here, we report the sequence and phylogenetic analysis of the H3N2 subtype of influenza A virus (IAV) in clinical samples collected from Riyadh, Saudi Arabia. Based on RT-PCR, IAV was found in 88 (28.3%) of the 311 samples screened. Of the 88-IAV positive samples, 43 (48.8%) were H1N1 subtype while the remaining 45 (51.2%) were found to be of the H3N2 subtype. Complete sequencing of HA and NA genes of H3N2 revealed, twelve and nine amino acid (AA) substitutions respectively, and importantly, these variations are absent in the current vaccine strains. Based on the phylogenetic analysis, the majority of H3N2 strains were grouped in the same clades as the vaccine strains. Importantly, the N-glycosylation sites at AA 135(NSS) were found to be unique to 6 strains in the investigated HA1 protein and were absent in the current vaccine strains. These data may have significant clinical implications in designing novel and population-based vaccines for IAV and underscore the need for regular monitoring of efficacy of vaccines due to emerging variants. Full article

Background: Longitudinal humoral SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) immunity for up to 15 months due to vaccination, the efficacy of vaccination strategies (homologous, vector–vector versus heterologous, vector–mRNA), the influence of vaccination side effects, and the infection rate in German healthcare workers need to be investigated. Methods: In this study, 103 individuals vaccinated against SARS-CoV-2 were enrolled to examine their anti-SARS-CoV-2 anti-N- and anti-RBD/S1-Ig levels. A total of 415 blood samples in lithium heparin tubes were prospectively obtained, and a structured survey regarding medical history, type of vaccine, and vaccination reactions was conducted. Results: All participants demonstrated a humoral immune response, among whom no values decreased below the positivity cutoff. Five to six months after the third vaccination, three participants showed anti-RBD/S1 antibodies of less than 1000 U/mL. We observed higher levels for heterologous mRNA-/vector-based combinations compared to pure vector-based vaccination after the second vaccination, which is harmonized after a third vaccination with the mRNA-vaccine only in both cohorts. The incidence of vaccine breakthrough in a highly exposed cohort was 60.3%. Conclusion: Sustained long-term humoral immunity was observed, indicating the superiority of a heterologous mRNA-/vector-based combination compared to pure vector-based vaccination. There was longevity of anti-RBD/S1 antibodies of at least 4 and up to 7 months without external stimulus. Regarding vaccination reactogenity, the occurrence of local symptoms as pain at the injection site was increased after the first mRNA application compared to the vector–vector cohort with a general decrease in adverse events at later vaccination time points. Overall, a correlation between the humoral vaccination response and vaccination side effects was not observed. Despite the high prevalence of vaccine breakthroughs, these only occurred in the later course of the study when more infectious variants, which are, however, associated with milder courses, were present. These results provide insights into vaccine-related serologic responses, and the study should be expanded using additional vaccine doses and novel variants in the future. Full article

Due to the rapid development of COVID-19 vaccines, the world has faced a huge challenge with their general acceptance, including Poland. For this reason, we attempted to determine the sociodemographic factors influencing the decision of positive or negative attitudes toward COVID-19 vaccination. The analysis included 200,000 Polish participants—80,831 women (40.4%) and 119,169 men (59.6%). The results revealed that the most common reasons for vaccine refusal and hesitancy were the fear of post-vaccination complications and their safety (11,913/31,338, 38.0%; 9966/31,338, 31.8%). Negative attitudes were observed more often among male respondents with primary or secondary education (OR = 2.01, CI95% [1.86–2.17] and OR = 1.52, CI95% [1.41–1.63], respectively). On the other hand, older age ≥ 65 (OR = 3.69; 95%CI [3.44–3.96]), higher education level (OR = 2.14; 95%CI [2.07–2.22]), living in big cities with a range of 200,000–499,999 inhabitants and more than 500,000 inhabitants (OR = 1.57, CI95% [1.50–1.64] and OR = 1.90, CI95% [1.83–1.98], respectively), good physical conditions (OR = 2.05; CI95% [1.82–2.31]), and at last normal mental health conditions (OR = 1.67, CI95% [1.51–1.85]) were significantly associated with COVID-19 vaccine acceptance. Our study indicates which population group should be further supplied with data and information by health education, the government, and healthcare professionals to alleviate the negative attitude toward COVID-19 vaccines. Full article

The COVID-19 pandemic has caused havoc all around the world. The causative agent of COVID-19 is the novel form of the coronavirus (CoV) named SARS-CoV-2, which results in immune system disruption, increased inflammation, and acute respiratory distress syndrome (ARDS). T cells have been important components of the immune system, which decide the fate of the COVID-19 disease. Recent studies have reported an important subset of T cells known as regulatory T cells (Tregs), which possess immunosuppressive and immunoregulatory properties and play a crucial role in the prognosis of COVID-19 disease. Recent studies have shown that COVID-19 patients have considerably fewer Tregs than the general population. Such a decrement may have an impact on COVID-19 patients in a number of ways, including diminishing the effect of inflammatory inhibition, creating an inequality in the Treg/Th17 percentage, and raising the chance of respiratory failure. Having fewer Tregs may enhance the likelihood of long COVID development in addition to contributing to the disease’s poor prognosis. Additionally, tissue-resident Tregs provide tissue repair in addition to immunosuppressive and immunoregulatory activities, which may aid in the recovery of COVID-19 patients. The severity of the illness is also linked to abnormalities in the Tregs’ phenotype, such as reduced expression of FoxP3 and other immunosuppressive cytokines, including IL-10 and TGF-beta. Hence, in this review, we summarize the immunosuppressive mechanisms and their possible roles in the prognosis of COVID-19 disease. Furthermore, the perturbations in Tregs have been associated with disease severity. The roles of Tregs are also explained in the long COVID. This review also discusses the potential therapeutic roles of Tregs in the management of patients with COVID-19. Full article

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p < 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence. Full article

Background: Cervical cancer, the fourth most frequent cancer in women, is associated with the human papillomavirus (HPV). This study identifies risk factors and clinical findings for abnormal cervical cytology and histopathology in the Trinidad and Tobago populations. Some risk factors include early age of first coitus, a high number of sexual partners, high parity, smoking, and using certain medications, such as oral contraception. This study aims to identify the significance of Papanicolaou (pap) smears and the common risk factors that contribute to the development of premalignant and malignant cervical lesions. Method: A three-year retrospective, descriptive study of cervical cancer was conducted at the Eric Williams Medical Sciences Complex. The subject population included 215 female patients aged 18 years and older with the following documented abnormal cervical cytology: (ASCUS), ASC-H, LSIL, HSIL, Atypical Glandular cells, HPV, Adenocarcinoma, and Invasive Squamous Cell Carcinoma. Histopathology records were analysed for thirty-three of these patients. Patients’ information was recorded on data collection sheets adapted from the North Central Regional Health Authority’s cytology laboratory standardised reporting format request form. Results and Findings: The data were analysed via Statistical Package for Social Sciences (SPSS) software edition 23 using frequency tables and descriptive analysis. The mean sample age of the population was 36.7 years, the first age of coitus was 18.1 years, the number of sexual partners was 3.8, and the number of live births was 2. LSIL was the most popular abnormal finding, 32.6%, followed by HSIL, 28.8%, and ASCUS, 27.4%. Most histopathological reports resulted in CIN I and II. Conclusions: The significant risk factors observed for cytology abnormalities and premalignant lesions were early age of coitus, a high number of sexual partners, and no use of contraception. Patients mostly presented as asymptomatic despite obtaining abnormal cytology results. Hence, regular pap smear screening should continue to be highly encouraged. Full article

Mass vaccination against coronavirus disease 2019 (COVID-19) is a global health strategy to control the COVID-19 pandemic. With the increasing number of vaccinations, COVID-19 vaccine-associated lymphadenopathy (C19-VAL) has been frequently reported. Current findings emphasize the characteristics of C19-VAL. The mechanism of C19-VAL is complicated to explore. Accumulated reports separately show that C19-VAL incidence is associated with receiver age and gender, reactive change within lymph nodes (LN), etc. We constructed a systematic review to evaluate the associated elements of C19-VAL and provide the mechanism of C19-VAL. Articles were searched from PubMed, Web of Science and EMBASE by using the processing of PRISMA. The search terms included combinations of the COVID-19 vaccine, COVID-19 vaccination and lymphadenopathy. Finally, sixty-two articles have been included in this study. Our results show that days post-vaccination and B cell germinal center response are negatively correlated with C19-VAL incidence. The reactive change within LN is highly related to C19-VAL development. The study results suggested that strong vaccine immune response may contribute to the C19-VAL development and perhaps through the B cell germinal center response post vaccination. From the perspective of imaging interpretation, it is important to carefully distinguish reactive lymph nodes from metastatic lymph node enlargement through medical history collection or evaluation, especially in patients with underlying malignancy. Full article

Vaccines have proven to be the most cost-efficient and reasonable way to fight and exterminate virulent pathogens. Vaccines can be designed using a variety of platforms including inactivated/attenuated pathogen or subunits of it. The most recent COVID mRNA vaccines have employed nucleic acid sequences for the antigen of interest to combat the pandemic. Different vaccine platforms have been chosen for different licensed vaccines which all have shown their ability to induce durable immune responses and protection. In addition to platforms, different adjuvants have been used to strengthen the immunogenicity of vaccines. Among the delivery routes, intramuscular injection has been the most common for vaccination. In this review, we present a historical overview of the integrated consideration of vaccine platforms, adjuvants, and delivery routes in the success of vaccine development. We also discuss the advantages and limitations of each choice in the efficacy of vaccine development. Full article

Brucellosis is a zoonotic bacterial illness that affects humans and a variety of domestic animals, especially ruminants. It is mostly transmitted through the consumption of contaminated drinks, foods, undercooked meat, or unpasteurized milk or contact with infected animals. Therefore, the present study aimed to investigate the seroprevalence of brucellosis in camels, sheep, and goat herds in the Qassim region, Saudi Arabia, using commonly used diagnostic serological procedures such as the Rose Bengal test (RBT), complement fixation test (CFT), and enzyme-linked immunosorbent assay (ELISA). The seroprevalence of brucellosis in camels, sheep, and goats was determined in the selected areas using a cross-sectional study design and a total of 690 farm animals of both sexes of different ages from the three animal species (274 camels, 227 sheep, and 189 goats). According to RBT results, 65 sera were positive for brucellosis, including 15 (5.47%) for camels, 32 (14.09%) for sheep, and 18 (9.50%) for goats. CFT and c-ELISA were performed as confirmatory tests on positive samples resulting from RBT. With c-ELISA, 60 serum samples were confirmed positive, in 14 (5.10%), 30 (13.21%), and 16 (8.46%) camels, sheep, and goats, respectively. There were 59 serum samples confirmed as positive for CFT, including 14 (5.11%), 29 (12.77%), and 16 (8.46%) for camels, sheep, and goats, respectively. Overall, the highest seroprevalence of brucellosis was found in sheep while the least was found in camels from the three tests (RBT, c-ELISA, and CFT). The highest seroprevalence of brucellosis was found in sheep while the least seroprevalence was found in camels. There was also a higher seroprevalence of brucellosis among female animals than males as well as among old animals than young animals. The study, thus, demonstrates brucellosis seroprevalence among farm animals (camels, sheep, and goats) and the significance of intervention measures against brucellosis incidence in both humans and animals through the creation of public awareness and other relevant policy measures such as livestock vaccination, effective hygiene management, and adequate quarantine or serological analysis for newly introduced animals. Full article

Since the coronavirus disease (COVID-19) pandemic hit the globe in early 2020, we have steadily gained insight into its pathogenesis; thereby improving surveillance and preventive measures. In contrast to other respiratory viruses, neonates and young children infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have a milder clinical presentation, with only a small proportion needing hospitalization and intensive care support. With the emergence of novel variants and improved testing services, there has been a higher incidence of COVID-19 disease reported among children and neonates. Despite this, the proportion of young children with severe disease has not increased. Key mechanisms that protect young children from severe COVID-19 disease include the placental barrier, differential expression of angiotensin-converting enzyme 2 (ACE-2) receptors, immature immune response, and passive transfer of antibodies via placenta and human milk. Implementing mass vaccination programs has been a major milestone in reducing the global disease burden. However, considering the lower risk of severe COVID-19 illness in young children and the limited evidence about long-term vaccine safety, the risk–benefit balance in children under five years of age is more complex. In this review, we do not support or undermine vaccination of young children but outline current evidence and guidelines, and highlight controversies, knowledge gaps, and ethical issues related to COVID-19 vaccination in young children. Regulatory bodies should consider the individual and community benefits of vaccinating younger children in their local epidemiological setting while planning regional immunization policies. Full article

Anti-platelet factor 4 (anti-PF4) antibodies were identified as pathogenic antibodies for vaccine-induced immune thrombocytopenia and thrombosis (VITT) in subjects receiving ChAdOx1 nCoV-19 vaccinations. We performed a prospective cohort study to determine the prevalence of anti-PF4 and the effect of the ChAdOx1 nCoV-19 vaccine on anti-PF4 in healthy Thai subjects. Anti-PF4 antibodies were measured before and four weeks after receiving the first vaccination. Participants with detectable antibodies were scheduled for repeat anti-PF4 analysis at 12 weeks after the second vaccination. Of 396 participants, ten participants (2.53%; 95% confidence interval [CI], 1.22–4.59) were positive for anti-PF4 before receiving vaccinations. Twelve people (3.03%; 95% CI, 1.58–5.23) had detectable anti-PF4 after the first vaccination. There was no difference in the optical density (OD) values of anti-PF4 antibodies when comparisons were made between pre-vaccination and four weeks after the first vaccination (p = 0.0779). There was also no significant difference in OD values in participants with detectable antibodies. No subjects experienced thrombotic complications. Pain at the injection site was associated with an increased risk of being anti-PF4 positive at an odds ratio of 3.44 (95% CI, 1.06–11.18). To conclude, the prevalence of anti-PF4 was low in Thais and did not significantly change over time. Full article

(1) Background: Better understanding of post-/long-COVID and limitations in daily life due to the symptoms as well as the preventive potential of vaccinations is required. It is unclear whether the number of doses and timepoint interrelate with the trajectory of post-/long-COVID. Accordingly, we examined how many patients positively screened with post-/long-COVID were vaccinated and whether the vaccination status and the timepoint of vaccination in relation to the acute infection were related to post-/long-COVID symptom severity and patients’ functional status (i.e., perceived symptom severity, social participation, workability, and life satisfaction) over time. (2) Methods: 235 patients suffering from post-/long-COVID were recruited into an online survey in Bavaria, Germany, and assessed at baseline (T1), after approximately three weeks (T2), and approximately four weeks (T3). (3) Results: 3.5% were not vaccinated, 2.3% were vaccinated once, 20% twice, and 53.3% three times. Overall, 20.9% did not indicate their vaccination status. The timepoint of vaccination was related to symptom severity at T1, and symptoms decreased significantly over time. Being vaccinated more often was associated with lower life satisfaction and workability at T2. (4) Conclusions: This study provides evidence to get vaccinated against SARS-CoV-2, as it has shown that symptom severity was lower in those patients who were vaccinated prior to the infection compared to those getting infected prior to or at the same time of the vaccination. However, the finding that being vaccinated against SARS-CoV-2 more often correlated with lower life satisfaction and workability requires more attention. There is still an urgent necessity for appropriate treatment for overcoming long-/post-COVID symptoms efficiently. Vaccination can be part of prevention measures, and there is still a need for a communication strategy providing objective information about the usefulness and risks of vaccinations. Full article

This Review initiates a wide-ranging discussion over 2023 by selecting and exploring core themes to be investigated more deeply in papers submitted to the Vaccines Special Issue on the “Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs”. To tackle the SARS-CoV-2 pandemic, an acceleration of vaccine development across different technology platforms resulted in the emergency use authorization of multiple vaccines in less than a year. Despite this record speed, many limitations surfaced including unequal access to products and technologies, regulatory hurdles, restrictions on the flow of intellectual property needed to develop and manufacture vaccines, clinical trials challenges, development of vaccines that did not curtail or prevent transmission, unsustainable strategies for dealing with variants, and the distorted allocation of funding to favour dominant companies in affluent countries. Key to future epidemic and pandemic responses will be sustainable, global-public-health-driven vaccine development and manufacturing based on equitable access to platform technologies, decentralised and localised innovation, and multiple developers and manufacturers, especially in low- and middle-income countries (LMICs). There is talk of flexible, modular pandemic preparedness, of technology access pools based on non-exclusive global licensing agreements in exchange for fair compensation, of WHO-supported vaccine technology transfer hubs and spokes, and of the creation of vaccine prototypes ready for phase I/II trials, etc. However, all these concepts face extraordinary challenges shaped by current commercial incentives, the unwillingness of pharmaceutical companies and governments to share intellectual property and know-how, the precariousness of building capacity based solely on COVID-19 vaccines, the focus on large-scale manufacturing capacity rather than small-scale rapid-response innovation to stop outbreaks when and where they occur, and the inability of many resource-limited countries to afford next-generation vaccines for their national vaccine programmes. Once the current high subsidies are gone and interest has waned, sustaining vaccine innovation and manufacturing capability in interpandemic periods will require equitable access to vaccine innovation and manufacturing capabilities in all regions of the world based on many vaccines, not just “pandemic vaccines”. Public and philanthropic investments will need to leverage enforceable commitments to share vaccines and critical technology so that countries everywhere can establish and scale up vaccine development and manufacturing capability. This will only happen if we question all prior assumptions and learn the lessons offered by the current pandemic. We invite submissions to the special issue, which we hope will help guide the world towards a global vaccine research, development, and manufacturing ecosystem that better balances and integrates scientific, clinical trial, regulatory, and commercial interests and puts global public health needs first. Full article

Background: The importance of immunization for child survival underscores the need to eliminate immunization inequalities. Few existing studies of inequalities use approaches that view the challenges and potential solutions from the perspective of caregivers. This study aimed to identify barriers and context-appropriate solutions by engaging deeply with caregivers, community members, health workers, and other health system actors through participatory action research, intersectionality, and human-centered design lenses. Methods: This study was conducted in the Demographic Republic of Congo, Mozambique and Nigeria. Rapid qualitative research was followed by co-creation workshops with study participants to identify solutions. We analyzed the data using the UNICEF Journey to Health and Immunization Framework. Results: Caregivers of zero-dose and under-immunized children faced multiple intersecting and interacting barriers related to gender, poverty, geographic access, and service experience. Immunization programs were not aligned with needs of the most vulnerable due to the sub-optimal implementation of pro-equity strategies, such as outreach vaccination. Caregivers and communities identified feasible solutions through co-creation workshops and this approach should be used whenever possible to inform local planning. Conclusions: Policymakers and managers can integrate HCD and intersectionality mindsets into existing planning and assessment processes, and focus on overcoming root causes of sub-optimal implementation. Full article

Strategies to combat COVID-19 include vaccines and Monoclonal Antibody Therapy. While vaccines aim to prevent development of symptoms, Monoclonal Antibody Therapy aims to prevent the progression of mild to severe disease. An increasing number of COVID-19 infections in vaccinated patients raised the question of whether vaccinated and unvaccinated COVID-19 positive patients respond differently to Monoclonal Antibody Therapy. The answer can help prioritize patients if resources are scarce. We performed a retrospective study to evaluate and compare the outcomes and risks for disease progression between vaccinated and unvaccinated COVID-19 patients treated with Monoclonal Antibody Therapy by measuring the number of Emergency Department visits and hospitalizations within 14 days as well as the progression to severe disease, defined through the Intensive Care Unit admissions within 14 days, and death within 28 days from the Monoclonal Antibody infusion. From 3898 included patients, 2009 (51.5%) were unvaccinated at the time of Monoclonal Antibody infusion. Unvaccinated patients had more Emergency Department visits (217 vs. 79, p < 0.0001), hospitalizations (116 vs. 38, p < 0.0001), and progression to severe disease (25 vs. 19, p = 0.016) following treatment with Monoclonal Antibody Therapy. After adjustment for demographics and comorbidities, unvaccinated patients were 2.45 times more likely to seek help in the Emergency Department and 2.70 times more likely to be hospitalized. Our data suggest the added benefit between the COVID-19 vaccine and Monoclonal Antibody Therapy. Full article

Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that causes systemic inflammation, autoimmunity, and joint abnormalities that result in permanent disability. Exosomes are nanosized extracellular particles found in mammals (40–100 nm). They are a transporter of lipids, proteins, and genetic material involved in mammalian cell–cell signaling, biological processes, and cell signaling. Exosomes have been identified as playing a role in rheumatoid arthritis-related joint inflammation (RA). Uniquely functioning extracellular vesicles (EVs) are responsible for the transport of autoantigens and mediators between distant cells. In addition, paracrine factors, such as exosomes, modulate the immunomodulatory function of mesenchymal stem cells (MSCs). In addition to transporting genetic information, exosomes convey miRNAs between cells and have been studied as drug delivery vehicles. In animal models, it has been observed that MSCs secrete EVs with immunomodulatory properties, and promising results have been observed in this area. By understanding the diversity of exosomal contents and their corresponding targets, it may be possible to diagnose autoimmune diseases. Exosomes can be employed as diagnostic biomarkers for immunological disorders. We here discuss the most recent findings regarding the diagnostic, prognostic, and therapeutic potential of these nanoparticles in rheumatoid arthritis and provide an overview of the evidence pertaining to the biology of exosomes in RA. Full article

Background: Specific vaccines are indicated for immunocompromised patients (ICPs) due to their vulnerability to infections. Recommendation of these vaccines by healthcare professionals (HCPs) is a crucial facilitator for vaccine uptake. Unfortunately, the responsibilities to recommend and administer these vaccines are not clearly allocated among HCPs involved in the care of adult ICPs. We aimed to evaluate HCPs’ opinions on directorship and their role in facilitating the uptake of medically indicated vaccines as a basis to improve vaccination practices. Methods: A cross-sectional survey was performed among in-hospital medical specialists (MSs), general practitioners (GPs), and public health specialists (PHSs) in the Netherlands to assess their opinion on directorship and the implementation of vaccination care. Additionally, perceived barriers, facilitators, and possible solutions to improve vaccine uptake were investigated. Results: In total, 306 HCPs completed the survey. HCPs almost unanimously (98%) reported that according to them, the primary treating physician is responsible for recommending medically indicated vaccines. Administering these vaccines was seen as a more shared responsibility. The most important barriers experienced by HCPs in recommending and administering were reimbursement problems, a lack of a national vaccination registration system, insufficient collaboration among HCPs, and logistical problems. MSs, GPs and PHSs all mentioned the same three solutions as important strategies to improve vaccination practices, i.e., reimbursement of vaccines, reliable and easily accessible registration of received vaccines, and arrangements for collaboration among the different HCPs that are involved in care. Conclusion: The improvement in vaccination practices in ICPs should focus on better collaboration among MSs, GPs, and PHSs, who should know each other’s expertise; clear agreement on responsibility; reimbursement for vaccines; and the availability of clear registration of vaccination history. Full article

Gender-based inequities in immunization impede the universal coverage of childhood vaccines. Leveraging data from the Government of Sindh’s Electronic Immunization Registry (SEIR), we estimated inequalities in immunization for males and females from the 2019–2022 birth cohorts in Pakistan. We computed male-to-female (M:F) and gender inequality ratios (GIR) Tfor enrollment, vaccine coverage, and timeliness. We also explored the inequities by maternal literacy, geographic location, mode of vaccination delivery, and gender of vaccinators. Between 1 January 2019, and 31 December 2022, 6,235,305 children were enrolled in the SEIR, 52.2% males and 47.8% females. We observed a median M:F ratio of 1.03 at enrollment and at Penta-1, Penta-3, and Measles-1 vaccinations, indicating more males were enrolled in the immunization system than females. Once enrolled, a median GIR of 1.00 indicated similar coverage for females and males over time; however, females experienced a delay in their vaccination timeliness. Low maternal education; residing in remote-rural, rural, and slum regions; and receiving vaccines at fixed sites, as compared to outreach, were associated with fewer females being vaccinated, as compared to males. Our findings suggeste the need to tailor and implement gender-sensitive policies and strategies for improving equity in immunization, especially in vulnerable geographies with persistently high inequalities. Full article

Background: Vaccines for SARS-CoV-2 have been critical for preventing disease. Previous research showed patients with diabetes have impaired immunity. This study aimed to determine the immunity to coronavirus after CoronaVac by comparing patients with type 2 diabetes (T2D) and healthcare workers (HCW). Materials and methods: A prospective cohort study evaluated immune responses and safety after two doses of CoronaVac in T2D and HCW groups at Chulabhorn Hospital. The levels of total antibodies against the receptor-binding domain (anti-RBD) of the SARS-CoV-2 spike protein at baseline and 4 weeks after vaccination were collected. The level of anti-RBD concentrations was reported as geometric mean concentration (GMC) and compared between groups using the geometric mean ratio (GMR). Results: 81 participants were included; 27 had T2D and 54 were HCW. After complete vaccination, anti-RBD concentrations were not significantly different between T2D (57.68 binding antibody units (BAU)/mL, 95% confidence interval (CI) = 29.08; 114.44) and HCW (72.49 BAU/mL, 95% CI = 55.77; 94.22) groups. Subgroup analysis showed the GMC of anti-RBD was significantly lower in T2D patients with dyslipidaemia (50.04 BAU/mL) than in T2D patients without dyslipidaemia (341.64 BAU/mL). Conclusions: The immune response at 4 weeks after two doses of CoronaVac did not significantly differ between patients with T2D and HCW. Full article

The coronavirus disease 2019 (COVID-19) pandemic imposed a pressing global threat. Vaccines against COVID-19 are a key tool to control the ongoing pandemic. The success of COVID-19 vaccination programs will largely depend on public willingness to receive the vaccine. This study aimed to evaluate the acceptability of COVID-19 vaccines among university students and lecturers in four different provinces of Indonesia. An anonymous, cross-sectional study was conducted online among university students and lecturers in Indonesia between 23 December 2020 and 15 February 2021. Of 3433 respondents, 50.3% stated that they would accept COVID-19 vaccination, while 10.7% expressed unwillingness and 39% were not sure about receiving the vaccine. Concern regarding the side effects after COVID-19 vaccination was the main reason among the participants for not willing to receive the vaccine. Being male, associated with the health sector, having a higher monthly expenditure and having health insurance could increase the acceptability of the COVID-19 vaccine. Low trust in the government and low confidence towards vaccine safety and efficacy could hinder participants’ decision to be vaccinated. Simple, clear and fact-based information from trusted sources on a regular basis will be important for building confidence towards the COVID-19 vaccination program in Indonesia. Full article