-
Vaccines Jun 2024Although vaccines address critical public health needs, inter-individual differences in responses are not always considered in their development. Understanding the...
Although vaccines address critical public health needs, inter-individual differences in responses are not always considered in their development. Understanding the underlying basis for these differences is needed to optimize vaccine effectiveness and ultimately improve disease control. In this pilot study, pre- and post-antiviral immunological and gut microbiota features were characterized to examine inter-individual differences in SARS-CoV-2 mRNA vaccine response. Blood and stool samples were collected before administration of the vaccine and at 2-to-4-week intervals after the first dose. A cohort of 14 adults was separated into two groups based on neutralizing antibody levels (high [HN] or low [LN]) at 10 weeks following vaccination. Bivariate correlation analysis was performed to examine associations between gut microbiota, inflammation, and neutralization capacity at that timepoint. These analyses revealed significant differences in gut microbiome composition and inflammation states pre-vaccination, which predicted later viral neutralization capacity, with certain bacterial taxa, such as those in the genus , found at higher abundance in the LN vs HN group that were also negatively correlated with a panel of inflammatory factors such as IL-17, yet positively correlated with plasma levels of the high mobility group box 1 (HMGB-1) protein at pre-vaccination. In particular, we observed a significant inverse relationship (Pearson = -0.54, = 0.03) between HMGB-1 pre-vaccination and neutralization capacity at 10 weeks post-vaccination. Consistent with known roles as mediators of inflammation, our results altogether implicate HMGB-1 and related gut microbial signatures as potential biomarkers in predicting SARS-CoV-2 mRNA vaccine effectiveness measured by the production of viral neutralization antibodies.
PubMed: 38932366
DOI: 10.3390/vaccines12060637 -
Vaccines Jun 2024Inactivated and live attenuated vaccines are the mainstays of preventing viral poultry diseases. However, the development of recombinant DNA technology in recent years... (Review)
Review
Inactivated and live attenuated vaccines are the mainstays of preventing viral poultry diseases. However, the development of recombinant DNA technology in recent years has enabled the generation of recombinant virus vector vaccines, which have the advantages of preventing multiple diseases simultaneously and simplifying the vaccination schedule. More importantly, some can induce a protective immune response in the presence of maternal antibodies and offer long-term immune protection. These advantages compensate for the shortcomings of traditional vaccines. This review describes the construction and characterization of primarily poultry vaccine vectors, including fowl poxvirus (FPV), fowl adenovirus (FAdV), Newcastle disease virus (NDV), Marek's disease virus (MDV), and herpesvirus of turkey (HVT). In addition, the pathogens targeted and the immunoprotective effect of different poultry recombinant virus vector vaccines are also presented. Finally, this review discusses the challenges in developing vector vaccines and proposes strategies for improving immune efficacy.
PubMed: 38932359
DOI: 10.3390/vaccines12060630 -
Vaccines Jun 2024There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced widespread SARS-CoV-2 infection before vaccine...
There are few data on the real-world effectiveness of COVID-19 vaccines and boosting in Africa, which experienced widespread SARS-CoV-2 infection before vaccine availability. We assessed the association between vaccination and severe COVID-19 in the Western Cape, South Africa, in an observational cohort study of >2 million adults during 2020-2022. We described SARS-CoV-2 testing, COVID-19 outcomes, and vaccine uptake over time. We used multivariable cox models to estimate the association of BNT162b2 and Ad26.COV2.S vaccination with COVID-19-related hospitalization and death, adjusting for demographic characteristics, underlying health conditions, socioeconomic status proxies, and healthcare utilization. We found that by the end of 2022, 41% of surviving adults had completed vaccination and 8% had received a booster dose. Recent vaccination was associated with notable reductions in severe COVID-19 during periods dominated by Delta, and Omicron BA.1/2 and BA.4/5 (sub)lineages. During the latest Omicron BA.4/5 wave, within 3 months of vaccination or boosting, BNT162b2 and Ad26.COV2.S were each 84% effective against death (95% CIs: 57-94 and 49-95, respectively). However, distinct reductions of effectiveness occurred at longer times post completing or boosting vaccination. Results highlight the importance of continued emphasis on COVID-19 vaccination and boosting for those at high risk of severe COVID-19, even in settings with widespread infection-induced immunity.
PubMed: 38932357
DOI: 10.3390/vaccines12060628 -
Vaccines Jun 2024Chagas disease, caused by the protozoan , remains a major public health challenge affecting millions in Latin America and worldwide. Although significant progress has...
Chagas disease, caused by the protozoan , remains a major public health challenge affecting millions in Latin America and worldwide. Although significant progress has been made in vector control, no vaccine exists to prevent infection or mitigate disease pathogenesis. We developed a rationally designed chimeric protein vaccine, N-Tc52/TSkb20, incorporating immunodominant epitopes from two antigens, the amino-terminal portion of Tc52 and the TSkb20 epitope derived from trans-sialidase. The objectives of this study were to construct and characterize the antigen and evaluate its protective potential in an immunoprophylactic murine model of infection. The N-Tc52/TSkb20 protein was recombinantly expressed in and its identity was confirmed using mass spectrometry and Western blotting. Immunization with the chimeric protein significantly controlled parasitemia and reduced the heart, colon, and skeletal muscle parasite burdens compared to non-vaccinated mice. Protection was superior to vaccination with the individual parental antigen components. Mechanistically, the vaccine induced potent CD8+ T-cell and IFNγ responses against the incorporated epitopes and a protective IgG antibody profile. A relatively low IL-10 response favored early parasite control. These results validate the promising multi-epitope approach and support the continued development of this type of rational vaccine design strategy against Chagas disease.
PubMed: 38932350
DOI: 10.3390/vaccines12060621 -
Vaccines Jun 2024(Pg), a Gram-negative anaerobic bacterium found in dental plaque biofilm within periodontal pockets, is the primary pathogenic microorganism responsible for chronic... (Review)
Review
(Pg), a Gram-negative anaerobic bacterium found in dental plaque biofilm within periodontal pockets, is the primary pathogenic microorganism responsible for chronic periodontitis. Infection by Pg significantly impacts the development and progression of various diseases, underscoring the importance of eliminating this bacterium for effective clinical treatment. While antibiotics are commonly used to combat Pg, the rise of antibiotic resistance poses a challenge to complete eradication. Thus, the prevention of Pg infection is paramount. Research suggests that surface antigens of Pg, such as fimbriae, outer membrane proteins, and gingipains, can potentially be utilized as vaccine antigens to trigger protective immune responses. This article overviews these antigens, discusses advancements in mucosal adjuvants (including immunostimulant adjuvants and vaccine-delivery adjuvants), and their application in Pg vaccine development. Furthermore, the review examines the advantages and disadvantages of different immune pathways and common routes of Pg vaccine immunization. By summarizing the current landscape of Pg vaccines, addressing existing challenges, and highlighting the potential of mucosal vaccines, this review offers new insights for the advancement and clinical implementation of Pg vaccines.
PubMed: 38932348
DOI: 10.3390/vaccines12060619 -
Vaccines Jun 2024Bovine alphaherpesvirus 1 (BoAHV-1) infection affects the production and reproductive performance of dairy and beef livestock, resulting in considerable economic losses....
Bovine alphaherpesvirus 1 (BoAHV-1) infection affects the production and reproductive performance of dairy and beef livestock, resulting in considerable economic losses. In addition to biosecurity measures, vaccination programs are effective strategies for controlling and preventing BoAHV-1 infection and transmission. We evaluated the serological immune response against BoAHV-1 induced by eight different formulations of commercial vaccines: three modified live vaccines and five killed vaccines containing BoAHV type 1 or types 1 and 5. In the first experiment, 50 BoAHV-1-seronegative guinea pigs were assigned to eight groups; each individual in the treatment groups received two doses (one-fifth of the bovine dose). The second experiment was conducted using 29 crossbred Holstein × Gir heifers in four groups of six to nine animals each. The serological immune response against BoAHV-1 was measured using virus neutralization and enzyme-linked immunosorbent assays to measure the total IgG against BoAHV. We evaluated the effects of the vaccine, time, and interaction of the vaccine and time on neutralizing antibodies against BoAHV-1. Killed vaccines produced low levels of antibodies against BoAHV-1, whereas modified live vaccines produced high levels of antibodies capable of providing neutralizing titers in the vaccinated animals, with the thermosensitive modified live vaccine showing the highest levels of antibodies.
PubMed: 38932344
DOI: 10.3390/vaccines12060615 -
Vaccines Jun 2024We report on a highly significant, positive association between anthrax vaccination and occurrence of Gulf War Illness (GWI) in 111 Gulf War veterans (42 with GWI and 69...
We report on a highly significant, positive association between anthrax vaccination and occurrence of Gulf War Illness (GWI) in 111 Gulf War veterans (42 with GWI and 69 controls). GWI was diagnosed in 47.1% of vaccinated veterans but only in 17.2% of non-vaccinated veterans (Pearson = 7.08, = 0.008; odds ratio = 3.947; relative risk = 2.617), with 1.6x higher GWI symptom severity in vaccinated veterans ( = 0.007, F-test in analysis of covariance). Next, we tested the hypothesis that the susceptibility to GWI following anthrax vaccination could be due to inability to make antibodies against the anthrax protective antigen (PA), the key protein contained in the vaccine. Since the first step in initiating antibody production would be the binding of PA peptide fragments (typically 15-amino acid long [15-mer]) to peptide-binding motifs of human leukocyte antigen (HLA) Class II molecules, we assessed the binding-motif affinities of such HLA specific molecules to all linear 15-mer peptide fragments of the anthrax PA. We identified a total of 58 HLA Class II alleles carried by the veterans in our sample and found that, of those, 18 (31%) were present in the vaccinated group that did not develop GWI but were absent from the vaccinated group who developed GWI. Remarkably, in silico analyses revealed very high binding affinities of peptide-binding motifs of those 18 HLA alleles with fragments of anthrax vaccine PA, leading to the successful production of anti-PA antibodies. Conversely, the absence of these protective HLA alleles points to a reduced ability to develop antibodies against PA, thus resulting in harmful PA persistence and development of GWI.
PubMed: 38932342
DOI: 10.3390/vaccines12060613 -
Vaccines Jun 2024Introducing new recombinant protein antigens to existing pediatric combination vaccines is important in improving coverage and affordability, especially in low- and...
Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges.
Introducing new recombinant protein antigens to existing pediatric combination vaccines is important in improving coverage and affordability, especially in low- and middle-income countries (LMICs). This case-study highlights the analytical and formulation challenges encountered with three recombinant non-replicating rotavirus vaccine (NRRV) antigens (t-NRRV formulated with Alhydrogel adjuvant, AH) combined with a mock multidose formulation of a pediatric pentavalent vaccine used in LMICs. This complex formulation contained (1) vaccine antigens (i.e., whole-cell pertussis (wP), diphtheria (D), tetanus (T), (Hib), and hepatitis B (HepB), (2) a mixture of aluminum-salt adjuvants (AH and Adju-Phos, AP), and (3) a preservative (thimerosal, TH). Selective, stability-indicating competitive immunoassays were developed to monitor binding of specific mAbs to each antigen, except wP which required the setup of a mouse immunogenicity assay. Simple mixing led to the desorption of t-NRRV antigens from AH and increased degradation during storage. These deleterious effects were caused by specific antigens, AP, and TH. An AH-only pentavalent formulation mitigated t-NRRV antigen desorption; however, the Hib antigen displayed previously reported AH-induced instability. The same rank-ordering of t-NRRV antigen stability (P[8] > P[4] > P[6]) was observed in mock pentavalent formulations and with various preservatives. The lessons learned are discussed to enable future multidose, combination vaccine formulation development with new vaccine candidates.
PubMed: 38932338
DOI: 10.3390/vaccines12060609 -
Vaccines Jun 2024The Bursa of Fabricius, an avian unique humoral immune organ, is instrumental to B cell development. Bursal-derived peptide BP9 fosters B-cell development and formation....
The Bursa of Fabricius, an avian unique humoral immune organ, is instrumental to B cell development. Bursal-derived peptide BP9 fosters B-cell development and formation. Yet, the exact mechanism wherein BP9 impacts B cell differentiation and antigenic presentation remains undefined. In this paper, B cell activation and differentiation in the spleen cells from mice immunized with the AIV vaccine and BP9 were detected following flow cytometry (FCM) analysis. Furthermore, the molecular mechanism of BP9 in B cell differentiation in vivo was investigated with RNA sequencing technology. To verify the potential functional mechanism of BP9 in the antigenic presentation process, the transcriptome molecular basis of chicken macrophages stimulated by BP9 was measured via high-throughput sequencing technology. The results proved that when given in experimental dosages, BP9 notably accelerated total B cells, and enhanced B-cell differentiation and plasma cell production. The gene expression profiles of B cells from mice immunized with 0.01 mg/mL BP9 and AIV vaccine disclosed that 0.01 mg/mL BP9 initiated the enrichment of several biological functions and significantly stimulated key B-cell pathways in immunized mice. Crucially, a total of 4093 differentially expressed genes were identified in B cells with BP9 stimulation, including 943 upregulated genes and 3150 downregulated genes. Additionally, BP9 induced various cytokine productions in the chicken macrophage HD11 cells and activated 9 upregulated and 20 downregulated differential miRNAs, which were involved in various signal and biological processes. Furthermore, BP9 stimulated the activation of multiple transcription factors in HD11 cells, which was related to antigen presentation processes. In summary, these results suggested that BP9 might promote B cell differentiation and induce antigen presentation, which might provide the valuable insights into the mechanism of B cell differentiation upon bursal-derived immunomodulating peptide stimulation and provide a solid experimental groundwork for enhancing vaccine-induced immunity.
PubMed: 38932336
DOI: 10.3390/vaccines12060607 -
Vaccines Jun 2024Porcine reproductive and respiratory syndrome (PRRS) remains a formidable challenge for the global pig industry. Caused by PRRS virus (PRRSV), this disease primarily... (Review)
Review
Porcine reproductive and respiratory syndrome (PRRS) remains a formidable challenge for the global pig industry. Caused by PRRS virus (PRRSV), this disease primarily affects porcine reproductive and respiratory systems, undermining effective host interferon and other immune responses, resulting in vaccine ineffectiveness. In the absence of specific antiviral treatments for PRRSV, vaccines play a crucial role in managing the disease. The current market features a range of vaccine technologies, including live, inactivated, subunit, DNA, and vector vaccines, but only modified live virus (MLV) and killed virus (KV) vaccines are commercially available for PRRS control. Live vaccines are promoted for their enhanced protective effectiveness, although their ability to provide cross-protection is modest. On the other hand, inactivated vaccines are emphasized for their safety profile but are limited in their protective efficacy. This review updates the current knowledge on PRRS vaccines' interactions with the host interferon system, and other immunological aspects, to assess their current status and evaluate advents in PRRSV vaccine development. It presents the strengths and weaknesses of both live attenuated and inactivated vaccines in the prevention and management of PRRS, aiming to inspire the development of innovative strategies and technologies for the next generation of PRRS vaccines.
PubMed: 38932335
DOI: 10.3390/vaccines12060606