Novel mumps virus epitopes reveal robust cytotoxic T cell responses after natural infection but not after vaccination.
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ABSTRACT:
SUBMITTER: Kaaijk P
PROVIDER: S-EPMC8249633 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Mumps is a vaccine-preventable disease but outbreaks have been reported in persons vaccinated with two doses of MMR vaccine. The objective was to describe the demographic features, vaccination effectiveness and genetic mumps virus diversity among laboratory-confirmed cases between 2007 and 2011 in Catalonia. METHODS:Cases and outbreaks of mumps notified to the notifiable diseases system of Catalonia between 2007 and 2011 retrospectively registered were included. Public health care centres provided written immunization records to regional public health staff to determine the vaccination history. Saliva and serum specimens were collected from suspected cases for laboratory-confirmation using real-time reverse-transcriptase PCR (rtRT-PCR) or serological testing. Phylogenetic analysis of the complete SH gene (316 nucleotides) and complete coding HN protein (1749 nucleotides) sequences was made. Categorical variables were compared using the Chi-square or Fisher's tests and continuous variables using the Student test. Vaccination effectiveness by number of MMR doses was estimated using the screening method. RESULTS:During the study period, 581 confirmed cases of mumps were notified (incidence rate 1.6 cases/100,000 persons-year), of which 60% were male. Three hundred sixty-four laboratory-confirmed cases were reported, of which 44% were confirmed by rtRT-PCR. Of the 289 laboratory-confirmed cases belonging to vaccination cohorts, 33.5% (97) had received one dose of MMR vaccine and 50% (145) two doses. Based on phylogenetic analyses of 316-nucleotide and 174-nucleotide SH sequences, the viruses belonging to viral genotypes were: genotype G (126), genotype D (23), genotype H (2), genotype F (2), genotype J (1), while one remained uncharacterized. Amino acid differences were detected between circulating strains and the Jeryl Lynn vaccine strains, although the majority of amino acid substitutions were genotype-specific. Fifty-one outbreaks were notified that included 324 confirmed mumps cases. Genotype G was the most frequent genotype detected. The family (35%), secondary schools (25%) and community outbreaks (18%) were the most frequent settings. CONCLUSIONS:Our study shows that genotype G viruses are the most prevalent in Catalonia. Most cases occurred in people who had received two doses of MMR, suggesting inadequate effectiveness of the Jeryl Lynn vaccine strain. The possible factors related are discussed.
| S-EPMC6842476 | biostudies-literature
Project description:Hantaan virus, the prototypic member of the Hantavirus genus, causes hemorrhagic fever with renal syndrome in humans. We examined the human memory T-lymphocyte responses of three donors who had previous laboratory-acquired infections with Hantaan virus. We demonstrated virus-specific responses in bulk cultures of peripheral blood mononuclear cells (PBMC) from all donors. Bulk T-cell responses were directed against either Hantaan virus nucleocapsid (N) or G1 protein, and these responses varied between donors. We established both CD4(+) and CD8(+) N-specific cell lines from two donors and CD4(+) G1-specific cell lines from a third donor. All CD8(+) cytotoxic T-lymphocyte (CTL) lines recognized one of two epitopes on the nucleocapsid protein: one epitope spanning amino acids 12 to 20 and the other spanning amino acids 421 to 429. The CTL lines specific for amino acids 12 to 20 were restricted by HLA B51, and those specific for amino acids 421 to 429 were restricted by HLA A1. The N-specific CTL lines isolated from these two donors included both Hantaan virus-specific CTLs and hantavirus cross-reactive CTLs. Responses to both epitopes are detectable in short-term bulk cultures of PBMC from one donor, and precursor frequency analysis confirms that CTLs specific for these epitopes are present at relatively high precursor frequencies in the peripheral T-cell pool. These data suggest that infection with Hantaan virus results in the generation of CTL to limited epitopes on the nucleocapsid protein and that infection also results in the generation of cross-reactive T-cell responses to distantly related hantaviruses which cause the distinct hantavirus pulmonary syndrome. This is the first demonstration of human T-lymphocyte responses to Hantaan virus.
| S-EPMC112585 | biostudies-literature
Project description:Zika virus (ZIKV) is a flavivirus primarily transmitted by Aedes species mosquitoes, first discovered in Africa in 1947, that disseminated through Southeast Asia and the Pacific Islands in the 2000s. The first ZIKV infections in the Americas were identified in 2014, and infections exploded through populations in Brazil and other countries in 2015/16. ZIKV infection during pregnancy can cause severe brain and eye defects in offspring, and infection in adults has been associated with higher risks of Guillain-Barré syndrome. We initiated a study to describe the natural history of Zika (the disease) and the immune response to infection, for which some results have been reported. In this paper, we identify ZIKV-specific CD4+ and CD8+ T cell epitopes that induce responses during infection. Two screening approaches were utilized: an untargeted approach with overlapping peptide arrays spanning the entire viral genome, and a targeted approach utilizing peptides predicted to bind human MHC molecules. Immunoinformatic tools were used to identify conserved MHC class I supertype binders and promiscuous class II binding peptide clusters predicted to bind 9 common class II alleles. T cell responses were evaluated in overnight IFN-γ ELISPOT assays. We found that MHC supertype binding predictions outperformed the bulk overlapping peptide approach. Diverse CD4+ T cell responses were observed in most ZIKV-infected participants, while responses to CD8+ T cell epitopes were more limited. Most individuals developed a robust T cell response against epitopes restricted to a single MHC class I supertype and only a single or few CD8+ T cell epitopes overall, suggesting a strong immunodominance phenomenon. Noteworthy is that many epitopes were commonly immunodominant across persons expressing the same class I supertype. Nearly all of the identified epitopes are unique to ZIKV and are not present in Dengue viruses. Collectively, we identified 31 immunogenic peptides restricted by the 6 major class I supertypes and 27 promiscuous class II epitopes. These sequences are highly relevant for design of T cell-targeted ZIKV vaccines and monitoring T cell responses to Zika virus infection and vaccination.
| S-EPMC10497216 | biostudies-literature
Project description:Vaccines based on Plasmodium falciparum apical membrane antigen 1 (AMA1) have failed due to extensive polymorphism in AMA1. To assess the strain-specificity of antibody responses to malaria infection and AMA1 vaccination, we designed protein and peptide microarrays representing hundreds of unique AMA1 variants. Following clinical malaria episodes, children had short-lived, sequence-independent increases in average whole-protein seroreactivity, as well as strain-specific responses to peptides representing diverse epitopes. Vaccination resulted in dramatically increased seroreactivity to all 263 AMA1 whole-protein variants. High-density peptide analysis revealed that vaccinated children had increases in seroreactivity to four distinct epitopes that exceeded responses to natural infection. A single amino acid change was critical to seroreactivity to peptides in a region of AMA1 associated with strain-specific vaccine efficacy. Antibody measurements using whole antigens may be biased towards conserved, immunodominant epitopes. Peptide microarrays may help to identify immunogenic epitopes, define correlates of vaccine protection, and measure strain-specific vaccine-induced antibodies.
| S-EPMC7054363 | biostudies-literature
Project description:Despite the importance of vaccinia virus in basic and applied immunology, our knowledge of the human immune response directed against this virus is very limited. CD4(+) T cell responses are an important component of immunity induced by current vaccinia-based vaccines, and likely will be required for new subunit vaccine approaches, but to date vaccinia-specific CD4(+) T cell responses have been poorly characterized, and CD4(+) T cell epitopes have been reported only recently. Classical approaches used to identify T cell epitopes are not practical for large genomes like vaccinia. We developed and validated a highly efficient computational approach that combines prediction of class II MHC-peptide binding activity with prediction of antigen processing and presentation. Using this approach and screening only 36 peptides, we identified 25 epitopes recognized by T cells from vaccinia-immune individuals. Although the predictions were made for HLA-DR1, eight of the peptides were recognized by donors of multiple haplotypes. T cell responses were observed in samples of peripheral blood obtained many years after primary vaccination, and were amplified after booster immunization. Peptides recognized by multiple donors are highly conserved across the poxvirus family, including variola, the causative agent of smallpox, and may be useful in development of a new generation of smallpox vaccines and in the analysis of the immune response elicited to vaccinia virus. Moreover, the epitope identification approach developed here should find application to other large-genome pathogens.
| S-EPMC2014795 | biostudies-literature
Project description:By preventing infectious diseases, vaccines contribute substantially to public health. Besides, they offer great opportunities to investigate human immune responses. This is particularly true for live-attenuated virus vaccines which cause resolving acute infections and induce robust immunity. The fact that one can precisely schedule the time-point of vaccination enables complete characterization of the immune response over time, short-term and over many years. The live-attenuated Yellow Fever virus vaccine strain YF-17D was developed in the 1930's and gave rise to the 17D-204 and 17DD vaccine sub-strains, administered to over 600 million individuals worldwide. YF vaccination causes a systemic viral infection, which induces neutralizing antibodies that last for a lifetime. It also induces a strong T cell response resembling the ones of acute infections, in contrast to most other vaccines. In spite of its use since 1937, learning how YF vaccination stimulates such strong and persistent immune responses has gained substantial knowledge only in the last decades. Here we summarize the current state of knowledge on the immune response to YF vaccination, and discuss its contribution as a human model to address complex questions on optimal immune responses.
| S-EPMC8475614 | biostudies-literature
Project description:(1) Background: Malaria, a vector-borne infectious disease, is caused by parasites of the Plasmodium genus, responsible for increased extreme morbidity and mortality rates. Despite advances in approved vaccines, full protection has not yet been achieved upon vaccination, thus the development of more potent and safe immuno-stimulating agents for malaria prevention is a goal to be urgently accomplished. We have focused our research on a strategy to identify Plasmodium spp. epitopes by naturally acquired human antibodies and rodent malaria infection models immunized with site-directed non-natural antigens. (2) Methods: Some predictive algorithms and bioinformatics tools resembling different biological environments, such as phagosome-lysosome proteolytic degradation, affinity, and the high frequency of malaria-resistant and -sensitive HLA-II alleles were regarded for the proper selection of epitopes and potential testing. Each epitope's binding profile to both host cells and HLA-II molecules was considered for such initial screening. (3) Results: Once selected, we define each epitope-peptide to be synthesized in terms of size and hydrophobicity, and introduced peptide-bond surrogates and non-natural amino acids in a site-directed fashion, and then they were produced by solid-phase peptide synthesis. Molecules were then tested by their antigenic and immunogenic properties compared to human sera from Colombian malaria-endemic areas. The antigenicity and protective capacity of each epitope-peptide in a rodent infection model were examined. The ability of vaccinated mice after being challenged with P. berghei ANKA and P. yoelii 17XL to control malaria led to the determination of an immune stimulation involving Th1 and Th1/Th2 mechanisms. In silico molecular dynamics and modeling provided some interactions insights, leading to possible explanations for protection due to immunization. (4) Conclusions: We have found evidence for proposing MSP1-modified epitopes to be considered as neutralizing antibody stimulators that are useful as probes for the detection of Plasmodium parasites, as well as for sub-unit components of a site-directed designed malaria vaccine candidate.
| S-EPMC10057838 | biostudies-literature
Project description:BackgroundOpsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder that is characterized by involuntary eye movements and myoclonus. OMS exhibits various etiologies, including paraneoplastic, parainfectious, toxic-metabolic, and idiopathic causes. The exact immunopathogenesis and pathophysiology of OMS are uncertain.Case reportWe report the case of a 19-year-old male who developed opsoclonus and myoclonus several days after a flu-like illness. Serological tests revealed acute mumps infection. The findings of cerebrospinal fluid examinations and brain magnetic resonance imaging were normal. During the early phase of the illness, he suffered from opsoclonus and myoclonus that was so severe as to cause acute renal failure due to rhabdomyolysis. After therapies including intravenous immunoglobulin, the patient gradually improved and had fully recovered 2 months later.ConclusionsThis is the first report of OMS associated with mumps infection in Korea. Mumps infection should be considered in patients with OMS.
| S-EPMC4101107 | biostudies-literature
Project description:BackgroundThe live measles vaccine has been associated with lower non-measles mortality and admissions in low-income countries. The live measles-mumps-rubella vaccine has also been associated with lower rate of admissions with any type of infection in Danish children; the association was strongest for admissions with lower respiratory infections.ObjectiveTo examine whether measles, mumps, and rubella (MMR) vaccination was associated with reduced rate of hospital contact related to respiratory syncytial virus (RSV) in a high-income country.MethodsNationwide cohort study of laboratory-confirmed RSV hospital contacts at age 14-23 months in all children born in Denmark 1997-2002 who had already received the vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) at the recommended ages of 3, 5, and 12 months.ResultsThe study included 888 RSV hospital contacts in 128,588 person years of follow up (rate 6.8/1000 person years). Having MMR as the most recent vaccine was associated with a reduced rate of RSV hospital contacts compared with having DTaP-IPV-Hib as the most recent vaccine (Incidence rate ratio (IRR), 0.75; 95% confidence interval (CI), 0.63-0.89). After adjustment for potential confounders including exact age in days the IRR was 0.78 (95% CI, 0.66-0.93). The adjusted IRR was 0.74 (95% CI, 0.60-0.92) in males and 0.84 (95% CI, 0.66-1.06) in females (P Interaction, 0.42). There was no association in the first month after MMR vaccination (adjusted IRR, 0.97; 95% CI, 0.76-1.24) but the adjusted IRR was 0.70 (95% CI, 0.58-0.85) from one month after MMR vaccination.ConclusionsMMR vaccination was associated with reduced rate of hospital contacts related to laboratory-confirmed RSV infection. Further research on the association between MMR vaccination and other unrelated pathogens are warranted.
| S-EPMC4270443 | biostudies-literature
Project description:Effective vaccine-induced immune responses are particularly essential in older adults who face an increased risk of immunosenescence. However, the complexity and variability of the human immune system make predicting vaccine responsiveness challenging. To address this knowledge gap, our study aimed to characterize immune profiles that are predictive of vaccine responsiveness using "immunotypes" as an innovative approach. We analyzed an extensive set of innate and adaptive immune cell subsets in the whole blood of 307 individuals (aged 25-92) pre- and post-influenza vaccination which we associated with day 28 hemagglutination inhibition (HI) antibody titers. Building on our previous work that stratified individuals into nine immunotypes based on immune cell subsets, we identified two pre-vaccination immunotypes associated with weak and one showing robust day 28 antibody response. Notably, the weak responders demonstrated HLA-DR+ T-cell signatures, while the robust responders displayed a high naïve-to-memory T-cell ratio and percentage of nonclassical monocytes. These specific signatures deepen our understanding of the relationship between the baseline of the immune system and its functional potential. This approach could enhance our ability to identify individuals at risk of immunosenescence. Our findings highlight the potential of pre-vaccination immunotypes as an innovative tool for informing personalized vaccination strategies and improving health outcomes, particularly for aging populations.
| S-EPMC10861208 | biostudies-literature