Dynamics of T-cell responses following COVID-19 mRNA vaccination and breakthrough infection in older adults DOI Creative Commons
Sneha Datwani, Rebecca Kalikawe, Francis Mwimanzi

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 16, 2023

ABSTRACT Introduction While older adults generally mount weaker antibody responses to a primary COVID-19 vaccine series, T-cell remain less well characterized in this population. We compared SARS-CoV-2 spike-specific after two- and three-dose mRNA vaccination subsequent breakthrough infection younger adults. Methods quantified CD4+ CD8+ T-cells reactive overlapping peptides spanning the ancestral spike protein 40 (median age 79) 50 health care workers 39), all naive, using an activation induced marker assay. were further assessed 24 participants, including 8 adults, who subsequently experienced their first infection. Results A third dose significantly boosted frequencies above two-dose levels did not differ between either dose. Multivariable analyses adjusting for sociodemographic, vaccine-related variables confirmed that was associated with impaired cellular responses. Instead, strongest predictors of post-third-dose corresponding post-second-dose frequencies. Breakthrough increased both T cell frequencies, comparable Exploratory revealed association HLA-A*02:03 higher post-vaccination which may be attributable numerous strong-binding HLA-A*02:03-specific epitopes spike. Conclusion Older robust vaccination, are following

Language: Английский

Relationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes DOI Creative Commons
Junqing Xie, Beatriz Mothe,

Marta Alcalde Herraiz

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 13, 2024

Abstract The rapid global distribution of COVID-19 vaccines, with over a billion doses administered, has been unprecedented. However, in comparison to most identified clinical determinants, the implications individual genetic factors on antibody responses post-COVID-19 vaccination for breakthrough outcomes remain elusive. Here, we conducted population-based study including 357,806 vaccinated participants high-resolution HLA genotyping data, and subset 175,000 serology test results. We confirmed prior findings that single nucleotide polymorphisms associated response are predominantly located Major Histocompatibility Complex region, expansive HLA-DQB1*06 gene alleles linked improved responses. our results did not support claim this mutation alone can significantly reduce risk general population. In addition, discovered validated six (A*03:01, C*16:01, DQA1*01:02, DQA1*01:01, DRB3*01:01, DPB1*10:01) independently influence demonstrated combined effect across genes outcomes. Lastly, estimated vaccine-induced positivity provides approximately 20% protection against infection 50% severity. These have immediate functional studies molecules inform future personalised strategies.

Language: Английский

Citations

9
Genome‐wide association studies of response and side effects to the BNT162b2 vaccine in Italian healthcare workers: Increased antibody levels and side effects in carriers of the HLA‐A*03:01 allele DOI Creative Commons
Chiara Magri, Eleonora Marchina, Emanuele Sansone

et al.

HLA, Journal Year: 2023, Volume and Issue: 102(6), P. 707 - 719

Published: July 19, 2023

The remarkable variability of response to vaccines against SARS-CoV-2 is apparent. present study aims estimate the extent which host genetic background contributes this in terms immune and side effects following administration BNT162b2 vaccine. We carried out a genome wide association (GWAS) by genotyping 873 Italian healthcare workers who underwent anti-SARS-CoV-2 vaccination with vaccine for whom information about spike antibodies titers were available. GWAS revealed significant between HLA locus Spike level at 2 months first dose (SNP: rs1737060; p = 9.80 × 10-11 ). In particular, we observed positive antibody levels presence HLA-A*03:01 allele. same allele was found associated 2-2.4-fold increased risk experiencing specific such as fever, chills myalgia 1.5-1.8-fold joint pain, nausea, fatigue, headache asthenia, independently age sex. This confirms that heterogeneity its are least partially influenced variants. information, integrated individual biological lifestyle-related correlates, could be use definition algorithms aimed identification subjects additional doses would particularly beneficial maintain immunity virus.

Language: Английский

Citations

11
Viral and immune profiles during the first wave of SARS-CoV-2 infection in hospitalized patients in Sardinia, Italy DOI Creative Commons
Giulietta Venturi, Alessandra Gallinaro, Claudia Fortuna

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 24, 2025

Abstract We performed a retrospective immunological analysis of the antibody response in serum and nasopharyngeal swabs (NPS) obtained from 46 individuals infected with ancestral SARS-CoV-2 Wuhan-Hu-1 strain during first COVID-19 wave Cagliari (Sardinia, Italy), 4-month follow-up after hospital admission. implemented comprehensive mucosal samples using assays established our laboratories. In NPS we evaluated viral load by real time PCR, presence kinetics anti-Spike IgG IgA ELISA as well their anti-Wuhan neutralization activity, showing induction persistence anti-viral immunity at level. Neutralizing antibodies were measured safe pseudovirus-based assay validated comparison standard test live SARS-CoV-2. cross-neutralizing against all major early variants concerns (VoC) sera. Of note, detected remarkable reduction neutralizing activity BA.1 compared to BA.2 BA.5 Omicron subvariants, which was confirmed sera an analogous cohort patients San Raffaele Milan, geographically distant region Italy, virus same period time.

Language: Английский

Citations

0
The Effect of HLA Polymorphism on Immune Response to SARS‐CoV‐2 Vaccination Within an Infection‐Naïve, Vulnerable Population With End‐Stage Renal Disease DOI Creative Commons

F. Shinewi May Erskine,

Katrina Spensley, Maria Prendecki

et al.

HLA, Journal Year: 2025, Volume and Issue: 105(2)

Published: Feb. 1, 2025

HLA genes exhibit a high degree of polymorphism, contributing to genetic variability known influence immune responses infection. Here we investigate associations between polymorphism and serological T-lymphocyte the BNT162b2 ChAdOx1 SARS-CoV-2 vaccines within population receiving maintenance haemodialysis (HD) for End-Stage Renal Disease (ESRD). Our primary objective was identify alleles associated with diminished T-cellular responsiveness vaccination. As secondary objective, type COVID-19 disease outcomes were investigated using an independent ESRD cohort (n = 327). This aimed determine if poor vaccine response also linked unfavourable infection outcomes. In main study, serum from 225 infection-naïve patients HLA-typed high-resolution Next Generation Sequencing, titres analysed presence spike glycoprotein-specific antibodies after two doses A subset 33) tested response. Overall, 89% 200) seroconverted, but only 18% 6) cellular subgroup had positive The class II DPB1*104:01, DRB1*04:03 DRB1*14:04 I B*08:01 B*18:01 found significantly correlate seronegativity, DQB1*06:01 correlated responsiveness. We unable analyse effect on outcome due sample size limitations. results suggest pathways further research begin elucidate relationship in vulnerable population.

Language: Английский

Citations

0
POLYMORPHISMS IN HLA GENES AMONG BRAZILIAN PATIENTS HOSPITALIZED WITH COVID-19: INSIGHTS FROM A MULTICENTRIC STUDY DOI

Gilcele de Campos Martin Berber,

Kevin Matheus Lima de Sarges, Thais Campos Dias da Cruz

et al.

Microbial Pathogenesis, Journal Year: 2025, Volume and Issue: unknown, P. 107542 - 107542

Published: April 1, 2025

Language: Английский

Citations

0
Molecular Mimicry and HLA Polymorphisms May Drive Autoimmunity in Recipients of the BNT-162b2 mRNA Vaccine: A Computational Analysis DOI Creative Commons
Rossella Talotta

Microorganisms, Journal Year: 2023, Volume and Issue: 11(7), P. 1686 - 1686

Published: June 28, 2023

After the start of worldwide COVID-19 vaccination campaign, there were increased reports autoimmune diseases occurring de novo after vaccination. This in silico analysis aimed to investigate presence protein epitopes encoded by BNT-162b2 mRNA vaccine, one most widely administered vaccines, which could induce autoimmunity predisposed individuals.The FASTA sequence vaccine served as key input Immune Epitope Database and Analysis Resource. Linear peptides with 90% BLAST homology selected, T-cell, B-cell, MHC-ligand assays without MHC restriction searched analyzed. HLA disease associations screened on HLA-SPREAD platform selecting only positive markers.By 7 May 2023, a total 5693 corresponding 21 viral but also human proteins found. The latter included CHL1, ENTPD1, MEAF6, SLC35G2, ZFHX2. Importantly, some autoepitopes may be presented alleles positively associated various immunological diseases.The product contains immunogenic that trigger phenomena individuals through molecular mimicry mechanism. Genotyping for help identify at risk. However, further wet-lab studies are needed confirm this hypothesis.

Language: Английский

Citations

9
Five doses of the mRNA vaccination potentially suppress ancestral-strain stimulated SARS-CoV2-specific cellular immunity: a cohort study from the Fukushima vaccination community survey, Japan DOI Creative Commons
Yuta Tani, Morihito Takita, Masatoshi Wakui

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 16, 2023

The bivalent mRNA vaccine is recommended to address coronavirus disease variants, with additional doses suggested for high-risk groups. However, the effectiveness, optimal frequency, and number of remain uncertain. In this study, we examined long-term cellular humoral immune responses following fifth administration severe acute respiratory syndrome 2 (SARS-CoV-2) in patients undergoing hemodialysis. To our knowledge, first study monitor data on immunity dynamics populations after five vaccination, including vaccine. Whereas most maintained throughout observation period, observed reduced reactivity as measured by ancestral-strain-stimulated ELISpot assay a subset patients. Half individuals (50%; 14/28) three months dose, despite acquiring immunity. absence relationship between positive controls T-Spot suggests that these alterations were specific SARS-CoV-2. multivariable analysis, participants aged ≥70 years showed marginally significant lower likelihood having reactive results. Notably, among 14 who received heterologous vaccines, 13 successfully acquired immunity, supporting effectiveness strategy. These findings provide valuable insights future vaccination strategies vulnerable populations. further research needed evaluate involvement tolerance exhaustion through repeated optimize immunization strategies.

Language: Английский

Citations

9
Humoral Immune Response to the SARS-CoV-2 Spike Protein Receptor Binding Motif Linear Epitopes DOI Open Access
M. Monteiro, Guilherme C. Lechuga, Paloma Napoleão-Pêgo

et al.

Published: Feb. 2, 2024

Abstract: The worldwide spread of SARS-CoV-2 has led to a significant economic and social burden on global scale. Even though the pandemic concluded, there remains apprehension regarding emergence highly transmissible variants capable evading immunity induced by either vaccination or prior infection. success viral penetration is specific amino acid residues Receptor Binding Motif (RBM) involved in attachment. This region interacts with cellular receptor ACE2, triggering neutralizing antibody (nAb) response. In this study, we have evaluated immunogenicity serum from individuals who received single dose combination different vaccines against original strain mutated linear RBM. Despite modest response wild-type RBM, Omicron exhibit four mutations RBM (S477N, T478K, E484A, F486V) that result even lower titers. primary immune responses observed were directed towards IgA IgG. While nAbs typically target RBD, our investigation unveiled reduced seroreactivity within RBD's crucial subregion, deficiency may implications for generation protective nAbs. Evaluation S1WT S2WT peptides binding using microscale thermophoresis revealed higher affinity (35 nM) sequence (GSTPCNGVEGFNCYF), which includes FNCY patch. Our findings suggest not an immunodominant vaccinated individuals. Comprehending intricate dynamics humoral response, its interplay evolution, host genetics formulating effective strategies, only targeting but also anticipating potential future coronaviruses.

Language: Английский

Citations

3
Humoral Immune Response to SARS-CoV-2 Spike Protein Receptor-Binding Motif Linear Epitopes DOI Creative Commons
M. Monteiro, Guilherme C. Lechuga, Paloma Napoleão-Pêgo

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(4), P. 342 - 342

Published: March 22, 2024

The worldwide spread of SARS-CoV-2 has led to a significant economic and social burden on global scale. Even though the pandemic concluded, apprehension remains regarding emergence highly transmissible variants capable evading immunity induced by either vaccination or prior infection. success viral penetration is due specific amino acid residues receptor-binding motif (RBM) involved in attachment. This region interacts with cellular receptor ACE2, triggering neutralizing antibody (nAb) response. In this study, we evaluated serum immunogenicity from individuals who received single dose combination different vaccines against original strain mutated linear RBM. Despite modest response wild-type RBM, Omicron exhibit four mutations RBM (S477N, T478K, E484A, F486V) that result even lower titers. primary immune responses observed were directed toward IgA IgG. While nAbs typically target RBD, our investigation unveiled reduced seroreactivity within RBD’s crucial subregion, deficiency may have implications for generation protective nAbs. An evaluation S1WT S2WT peptides binding using microscale thermophoresis revealed higher affinity (35 nM) sequence (GSTPCNGVEGFNCYF), which includes FNCY patch. Our findings suggest not an immunodominant vaccinated individuals. Comprehending intricate dynamics humoral response, its interplay evolution, host genetics formulating effective strategies, targeting only but also anticipating potential future coronaviruses.

Language: Английский

Citations

2
Dynamics of T-cell Responses Following COVID-19 mRNA Vaccination and Breakthrough Infection in Older Adults DOI Creative Commons
Sneha Datwani, Rebecca Kalikawe, Francis Mwimanzi

et al.

Pathogens and Immunity, Journal Year: 2023, Volume and Issue: 8(1), P. 117 - 135

Published: Nov. 17, 2023

Introduction: While older adults generally mount weaker antibody responses to a primary COVID-19 vaccine series, T-cell remain less well characterized in this population. We compared SARS-CoV-2 spike-specific after 2- and 3-dose mRNA vaccination subsequent breakthrough infection younger adults. Methods: quantified CD4+ CD8+ T-cells reactive overlapping peptides spanning the ancestral spike protein 40 (median age 79) 50 health care workers 39), all naive, using an activation-induced marker assay. were further assessed 24 participants, including 8 adults, who subsequently experienced their first infection. Results: A third dose significantly boosted frequencies above 2-dose levels did not differ between either dose. Multivariable analyses adjusting for sociodemographic, health, vaccine-related variables confirmed that was associated with impaired cellular responses. Instead, strongest predictors of post-third-dose corresponding post-second-dose frequencies. Breakthrough increased both frequencies, comparable Exploratory revealed association HLA-A*02:03 higher post-vaccination which may be attributable numerous strong-binding HLA-A*02:03-specific epitopes protein. Conclusion: Older robust vaccination, are following

Language: Английский

Citations

4