Vaccines

Research

18 pages, 2835 KiB

Open AccessArticle

Application of the Sponge Model Implants in the Study of Vaccine Memory in Mice Previously Immunized with LBSap

by Mariana Ferreira Lanna, Lucilene Aparecida Resende, Paula Mello De Luca, Wanessa Moreira Goes, Maykelin Fuentes Zaldívar, André Tetzl Costa, Walderez Ornelas Dutra, Alexandre Barbosa Reis, Olindo Assis Martins-Filho, Kenneth Jhon Gollob, Sandra Aparecida Lima de Moura, Edelberto Santos Dias, Érika Michalsky Monteiro, Denise Silveira-Lemos and Rodolfo Cordeiro Giunchetti

Vaccines 2024, 12(12), 1322; https://doi.org/10.3390/vaccines12121322 - 26 Nov 2024

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Abstract

Background/Objectives: Considering the large number of candidates in vaccine-testing studies against different pathogens and the amount of time spent in the preclinical and clinical trials, there is a pressing need to develop an improved in vivo system to quickly screen vaccine candidates. The [...] Read more.

Background/Objectives: Considering the large number of candidates in vaccine-testing studies against different pathogens and the amount of time spent in the preclinical and clinical trials, there is a pressing need to develop an improved in vivo system to quickly screen vaccine candidates. The model of a polyester–polyurethane sponge implant provides a rapid analysis of the specific stimulus–response, allowing the study of a compartmentalized microenvironment. The sponge implant’s defined measurements were standardized as a compartment to assess the immune response triggered by the vaccinal antigen. The LBSap vaccine (composed of Leishmania braziliensis antigens associated with saponin adjuvant) was used in the sponge model to assess the antigen-specific immunological biomarker, including memory generation after initial contact with the antigen. Methods: Mice strains (Swiss, BALB/c, and C57BL/6) were previously immunized using LBSap vaccine, followed by an antigenic booster performed inside the sponge implant. The sponge implants were assessed after 72 h, and the immune response pattern was analyzed according to leukocyte immunophenotyping and cytokine production. Results: After LBSap vaccination, the innate immune response of the antigenic booster in the sponge implants demonstrated higher levels in the Ly+ neutrophils and CD11c+ dendritic cells with reduced numbers of F4/80+ macrophages. Moreover, the adaptive immune response in Swiss mice demonstrated a high CD3+CD4+ T-cell frequency, consisting of an effector memory component, in addition to a cytoxicity response (CD3+CD8+ T cells), displaying the central memory biomarker. The major cell surface biomarker in the BALB/c mice strain was related to CD3+CD4+ effector memory, while the increased CD3+CD8+ effector memory was highlighted in C57/BL6. The cytokine profile was more inflammatory in Swiss mice, with the highest levels of IL-6, TNF, IFN-g, and IL-17, while the same cytokine was observed in in C57BL/6 yet modulated by enhanced IL-10 levels. Similar to Swiss mice, BALB/c mice triggered an inflammatory environment after the antigenic booster in the sponge implant with the increased levels in the ILL-6, TNF, and IFN-g. Conclusions: The findings emphasized the impact of genetic background on the populations engaged in immune responses, suggesting that this model can be utilized to enhance and track both innate and adaptive immune responses in vaccine candidates. Consequently, these results may inform the selection of the most suitable experimental model for biomolecule testing, taking into account how the unique characteristics of each mouse strain affect the immune response dynamics. Full article

(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)

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16 pages, 3406 KiB

Open AccessArticle

Design, Immunogenicity and Preclinical Efficacy of the ChAdOx1.COVconsv12 Pan-Sarbecovirus T-Cell Vaccine

by Edmund G.-T. Wee, Sarah Kempster, Deborah Ferguson, Joanna Hall, Claire Ham, Susan Morris, Alison Crook, Sarah C. Gilbert, Bette Korber, Neil Almond and Tomáš Hanke

Vaccines 2024, 12(9), 965; https://doi.org/10.3390/vaccines12090965 - 26 Aug 2024

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Abstract

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection pre-clinically and in humans. While deploying these spike-based vaccines saved millions of lives worldwide, it has [...] Read more.

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection pre-clinically and in humans. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1.COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses, which are delivered by replication-deficient vector ChAdOx1. It directs T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1.COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1.COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8⁺ T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the β-coronavirus family. Full article

(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)

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14 pages, 1503 KiB

Open AccessArticle

Relationship between Endotoxin Content in Vaccine Preclinical Formulations and Animal Welfare: An Extensive Study on Historical Data to Set an Informed Threshold

by Federica Baffetta, Raffaella Cecchi, Eva Guerrini, Simona Mangiavacchi, Gilda Sorrentino and Daniela Stranges

Vaccines 2024, 12(7), 815; https://doi.org/10.3390/vaccines12070815 - 22 Jul 2024

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Abstract

The most widely known pyrogen impurity in vaccines is the Gram-negative bacterial endotoxin lipopolysaccharide (LPS). When administered at toxic doses, endotoxin triggers inflammatory responses, which lead to endotoxic shock. The literature on endotoxic content (EC) for preclinical vaccines’ formulations used in animal studies [...] Read more.

The most widely known pyrogen impurity in vaccines is the Gram-negative bacterial endotoxin lipopolysaccharide (LPS). When administered at toxic doses, endotoxin triggers inflammatory responses, which lead to endotoxic shock. The literature on endotoxic content (EC) for preclinical vaccines’ formulations used in animal studies is very poor, and the recommended thresholds are solely based on commercial vaccine limits set for humans and are, therefore, not connected to the actual impact of EC on animal welfare for species used in preclinical research studies. An extensive study to evaluate the presence of a potential relationship between endotoxin content in formulations administered to mice (the most common species used in preclinical research studies) and their welfare was conducted to calculate an EC threshold for formulations of candidate vaccines. Three years of historical data, from more than 500 formulations of different antigen types (i.e., proteins, glycoconjugates, OMV/GMMA) injected into more than 5000 mice, was evaluated with two alternative statistical methodologies, both demonstrating that there is no significant relationship between actual endotoxin levels and mouse welfare. The calculation of thresholds was, therefore, performed by consistency versus formulations that demonstrated no impact on animal welfare. Full article

(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)

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18 pages, 627 KiB

Open AccessArticle

Clinical and Diagnostic Features of Post-Acute COVID-19 Vaccination Syndrome (PACVS)

by Anna Katharina Mundorf, Amelie Semmler, Harald Heidecke, Matthias Schott, Falk Steffen, Stefan Bittner, Karl J. Lackner, Karin Schulze-Bosse, Marc Pawlitzki, Sven Guenther Meuth, Frank Klawonn, Jana Ruhrländer and Fritz Boege

Vaccines 2024, 12(7), 790; https://doi.org/10.3390/vaccines12070790 - 18 Jul 2024

Cited by 1 | Viewed by 11556

Abstract

Post-acute COVID-19 vaccination syndrome (PACVS) is a chronic disease triggered by SARS-CoV-2 vaccination (estimated prevalence 0.02%). PACVS is discriminated from the normal post-vaccination state by altered receptor antibodies, most notably angiotensin II type 1 and alpha-2B adrenergic receptor antibodies. Here, we investigate the [...] Read more.

Post-acute COVID-19 vaccination syndrome (PACVS) is a chronic disease triggered by SARS-CoV-2 vaccination (estimated prevalence 0.02%). PACVS is discriminated from the normal post-vaccination state by altered receptor antibodies, most notably angiotensin II type 1 and alpha-2B adrenergic receptor antibodies. Here, we investigate the clinical phenotype using a study registry encompassing 191 PACVS-affected persons (159 females/32 males; median ages: 39/42 years). Unbiased clustering (modified Jaccard index) of reported symptoms revealed a prevalent cross-cohort symptomatology of malaise and chronic fatigue (>80% of cases). Overlapping clusters of (i) peripheral nerve dysfunction, dysesthesia, motor weakness, pain, and vasomotor dysfunction; (ii) cardiovascular impairment; and (iii) cognitive impairment, headache, and visual and acoustic dysfunctions were also frequently represented. Notable abnormalities of standard serum markers encompassing increased interleukins 6 and 8 (>80%), low free tri-iodine thyroxine (>80%), IgG subclass imbalances (>50%), impaired iron storage (>50%), and increased soluble neurofilament light chains (>30%) were not associated with specific symptoms. Based on these data, 131/191 participants fit myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and simultaneously also several other established dysautonomia syndromes. Furthermore, 31/191 participants fit none of these syndromes. In conclusion, PACVS could either be an outlier of ME/CFS or a dysautonomia syndrome sui generis. Full article

(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)

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18 pages, 7736 KiB

Open AccessArticle

Host Functional Response to a Prototypic Orally Delivered Self-Replicating Vaccine Platform

by Allison C. Vilander, Julia Burak, Darby Gilfillan, Gregg A. Dean and Zaid Abdo

Vaccines 2024, 12(7), 701; https://doi.org/10.3390/vaccines12070701 - 21 Jun 2024

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Abstract

The development of mucosal vaccines has been limited and could be aided by a systems vaccinology approach to identify platforms and adjuvant strategies that induce protective immune responses. The induction of local immune responses by mucosal-delivered vaccines has been difficult to evaluate from [...] Read more.

The development of mucosal vaccines has been limited and could be aided by a systems vaccinology approach to identify platforms and adjuvant strategies that induce protective immune responses. The induction of local immune responses by mucosal-delivered vaccines has been difficult to evaluate from peripheral samples, as systemic responses often do not correlate with the mucosal response. Here, we utilized transcriptomics in combination with Gene Set Enrichment Analysis (GSEA) to assess innate immune activation by an oral probiotic Lactobacillus acidophilus-based vaccine platform in mice. The goal was to explore the earliest immune responses elicited after oral immunization at the Peyer’s patch. Twenty-four hours after oral delivery of the L. acidophilus vaccine platform, we found an abundance of L. acidophilus at Peyer’s patches and detected expression of the vaccine viral proteins and adjuvants, confirming in vivo vaccine delivery. Compared to mice orally dosed with buffer or wild-type L. acidophilus, we identified enhanced responses in immune pathways related to cytokine and gene signaling, T and B cell activation, phagocytosis, and humoral responses. While more work is needed to correlate these pathways with protection from infection and/or disease, they indicate this method’s potential to evaluate and aid in the iterative development of next-generation mucosal vaccines. Full article

(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)

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21 pages, 27314 KiB

Open AccessArticle

Breakthrough Infections in SARS-CoV-2-Vaccinated Multiple Myeloma Patients Improve Cross-Protection against Omicron Variants

by Angelika Wagner, Erika Garner-Spitzer, Claudia Auer, Pia Gattinger, Ines Zwazl, René Platzer, Maria Orola-Taus, Peter Pichler, Fabian Amman, Andreas Bergthaler, Johannes B. Huppa, Hannes Stockinger, Christoph C. Zielinski, Rudolf Valenta, Michael Kundi and Ursula Wiedermann

Vaccines 2024, 12(5), 518; https://doi.org/10.3390/vaccines12050518 - 9 May 2024

Cited by 3 | Viewed by 1976

Abstract

Patients with multiple myeloma (MM) are a heterogenous, immunocompromised group with increased risk for COVID-19 morbidity and mortality but impaired responses to primary mRNA SARS-CoV-2 vaccination. The effects of booster vaccinations and breakthrough infections (BTIs) on antibody (Ab) levels and cross-protection to variants [...] Read more.

Patients with multiple myeloma (MM) are a heterogenous, immunocompromised group with increased risk for COVID-19 morbidity and mortality but impaired responses to primary mRNA SARS-CoV-2 vaccination. The effects of booster vaccinations and breakthrough infections (BTIs) on antibody (Ab) levels and cross-protection to variants of concern (VOCs) are, however, not sufficiently evaluated. Therefore, we analysed humoral and cellular vaccine responses in MM patients stratified according to disease stage/treatment into group (1) monoclonal gammopathy of undetermined significance, (2) after stem cell transplant (SCT) without immunotherapy (IT), (3) after SCT with IT, and (4) progressed MM, and in healthy subjects (prospective cohort study). In contrast to SARS-CoV-2 hu-1-specific Ab levels, Omicron-specific Abs and their cross-neutralisation capacity remained low even after three booster doses in a majority of MM patients. In particular, progressed MM patients receiving anti-CD38 mAb and those after SCT with IT were Ab low responders and showed delayed formation of spike-specific B memory cells. However, MM patients with hybrid immunity (i.e., vaccination and breakthrough infection) had improved cross-neutralisation capacity against VOCs, yet in the absence of severe COVID-19 disease. Our results indicate that MM patients require frequent variant-adapted booster vaccinations and/or changes to other vaccine formulations/platforms, which might have similar immunological effects as BTIs. Full article

(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)

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Review

Jump to: Research, Other

33 pages, 847 KiB

Open AccessReview

Vaccines for the Elderly and Vaccination Programs in Europe and the United States

by Cleo Anastassopoulou, Stefanos Ferous, Snežana Medić, Nikolaos Siafakas, Fotini Boufidou, Georgia Gioula and Athanasios Tsakris

Vaccines 2024, 12(6), 566; https://doi.org/10.3390/vaccines12060566 - 22 May 2024

Cited by 3 | Viewed by 2229

Abstract

The share of the elderly population is growing worldwide as life expectancy increases. Immunosenescence and comorbidities increase infectious diseases’ morbidity and mortality in older adults. Here, we aimed to summarize the latest findings on vaccines for the elderly against herpes zoster, influenza, respiratory [...] Read more.

The share of the elderly population is growing worldwide as life expectancy increases. Immunosenescence and comorbidities increase infectious diseases’ morbidity and mortality in older adults. Here, we aimed to summarize the latest findings on vaccines for the elderly against herpes zoster, influenza, respiratory syncytial virus (RSV), COVID-19, and pneumococcal disease and to examine vaccine recommendation differences for this age group in Europe and the United States. PubMed was searched using the keywords “elders” and “vaccine” alongside the disease/pathogen in question and paraphrased or synonymous terms. Vaccine recommendations were also sought in the European and US Centers for Disease Control and Prevention databases. Improved vaccines, tailored for the elderly, mainly by using novel adjuvants or by increasing antigen concentration, are now available. Significant differences exist between immunization policies, especially between European countries, in terms of the recipient’s age, number of doses, vaccination schedule, and implementation (mandatory or recommended). Understanding the factors that influence the immune response to vaccination in the elderly may help to design vaccines that offer long-term protection for this vulnerable age group. A consensus-based strategy in Europe could help to fill the gaps in immunization policy in the elderly, particularly regarding vaccination against RSV and pneumococcus. Full article

(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)

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Other

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11 pages, 599 KiB

Open AccessBrief Report

Seroprevalence Assessment of Anti-Varicella Antibodies among Adults in the Province of Florence (Italy)

by Angela Bechini, Marco Del Riccio, Cristina Salvati, Benedetta Bonito, Beatrice Zanella, Massimiliano Alberto Biamonte, Mario Bruschi, Johanna Alexandra Iamarino, Letizia Fattorini, Lorenzo Baggiani, Monica Della Fonte, Giovanna Mereu, Paolo Bonanni, Working Group and Sara Boccalini

Vaccines 2024, 12(9), 1056; https://doi.org/10.3390/vaccines12091056 - 16 Sep 2024

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Abstract

Background: Varicella infections follow a benign course in around 90% of cases, with more severe forms occurring in adults. To identify potential pockets of susceptibility and to improve targeted immunization strategies, this study aims to critically assess immunological status by evaluating varicella seroprevalence [...] Read more.

Background: Varicella infections follow a benign course in around 90% of cases, with more severe forms occurring in adults. To identify potential pockets of susceptibility and to improve targeted immunization strategies, this study aims to critically assess immunological status by evaluating varicella seroprevalence among adults (18–99 years) in the province of Florence (Italy), nearly a decade after Tuscany introduced the vaccination program. Methods: A convenience sample of 430 subjects aged 18 to 94 years (mean age 51.8 ± 18.8 years), stratified by age and sex (53.7% of subjects were female; N = 231), was collected between 2018 and 2019. Sero-analytical analyses were conducted utilizing EUROIMMUN Anti-VZV ELISA (IgG) kits. Results: Most of them were of Italian nationality (87.4%; N = 376). Among the 430 tested samples, 385 (89.5%) were positive and 39 (9.1%) were negative. The remaining six sera (1.4%), confirmed as equivocal, were excluded from further analysis. No significant differences were found based on sex (p-value = 0.706) or nationality (p-value = 0.112). The application of trend tests (Mantel–Haenszel; Kendall Tau-b) showed a significant trend (p < 0.024 and p < 0.032, respectively), with an increasing probability of finding a positive anti-varicella serological status passing from a lower age group (84.2%) to a higher one (93.0%). By considering the female population aged 18–49 years, the seroprevalence of anti-varicella antibodies was found to be 88.4%, with a susceptibility of 11.6%, highlighting the risk of acquiring infection during pregnancy. Conclusions: The introduction of varicella vaccination has had a significant impact on public health in Tuscany and in Italy more generally. However, further efforts should be made to reduce the number of individuals still susceptible in adulthood, with particular attention given to women of childbearing age and the promotion of vaccination through mass and social media and institutional websites. Full article

(This article belongs to the Special Issue Research on Immune Response and Vaccines: 2nd Edition)

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