Persistent Antibody Clonotypes Dominate the Serum Response to Influenza over Multiple Years and Repeated Vaccinations.
Ontology highlight
ABSTRACT:
SUBMITTER: Lee J
PROVIDER: S-EPMC6417944 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
Publications
Persistent Antibody Clonotypes Dominate the Serum Response to Influenza over Multiple Years and Repeated Vaccinations.
Lee Jiwon J Paparoditis Philipp P Horton Andrew P AP Frühwirth Alexander A McDaniel Jonathan R JR Jung Jiwon J Boutz Daniel R DR Hussein Dania A DA Tanno Yuri Y Pappas Leontios L Ippolito Gregory C GC Corti Davide D Lanzavecchia Antonio A Georgiou George G
Cell host & microbe 20190219 3
Humans are repeatedly exposed to influenza virus via infections and vaccinations. Understanding how multiple exposures and pre-existing immunity impact antibody responses is essential for vaccine development. Given the recent prevalence of influenza H1N1 A/California/7/2009 (CA09), we examined the clonal composition and dynamics of CA09 hemagglutinin (HA)-reactive IgG repertoire over 5 years in a donor with multiple influenza exposures. The anti-CA09 HA polyclonal response in this donor comprise ...[more]
Similar Datasets
Project description:Longitudinal proteomic analysis of H1N1 A/California/7/2009 (CA09) hemagglutinin (HA)-reactive serum IgG antibody repertoire over 5 years and multiple (yearly) vaccinations (both pre- and post-vaccination samples) in a donor. Dataset consists of steady-state (pre-vaccination at day 0) and peak-response (2-3 weeks post-vaccination) serum IgG samples enriched by affinity chromatography against hemagglutinin protein from H1 A/California/7/2009.
2018-11-08 | MSV000083120 | MassIVE
Project description:Previous studies have shown that repeated influenza vaccination can enhance susceptibility to subsequent infection with a drifted influenza virus strain. This paper seeks to further understanding of the interactions between influenza viruses and specific immune cells that accompany this phenomenon. The paper argues that repeated vaccination increases susceptibility to infection only in the context of a residual immunity induced by prior vaccination or infection. The results of computational analysis indicate that this is a dynamic consequence of interactions between vaccines, influenza viruses and specific immune cells. In particular, mathematical modelling was used to show that in the presence of residual immunity conferred by a vaccine administered in Canada in the 2013-2014 influenza season, the 2014-2015 season vaccine enhanced susceptibility to infection. Such infection enhancement occurs when the 2014-2015 vaccine boosts suppressive T-regulatory cells induced by the 2013-2014 vaccine, decreasing the strength of antibody responses to the infecting strain. Overall, the study suggests probable characteristics of infecting viruses and vaccines that make repeated influenza infections and vaccinations detrimental.
| S-EPMC8074957 | biostudies-literature
Project description:Seasonal influenza vaccine formulas change almost every year yet information about how this affects the antibody repertoire of vaccine recipients is inadequate. New vaccine virus strains are selected, replacing older strains to better match the currently circulating strains. But even while the vaccine is being manufactured the circulating strains can evolve. The ideal response to a seasonal vaccine would maintain antibodies toward existing strains that might continue to circulate, and to generate cross-reactive antibodies, particularly towards conserved influenza epitopes, potentially limiting infections caused by newly evolving strains. Here we use the hemagglutination inhibition assay to analyze the antibody repertoire in subjects vaccinated two years in a row with either identical vaccine virus strains or with differing vaccine virus strains. The data indicates that changing the vaccine formulation results in an antibody repertoire that is better able to react with strains emerging after the vaccine virus strains are selected. The effect is observed for both influenza A and B strains in groups of subjects vaccinated in three different seasons. Analyses include stratification by age and sex.
| S-EPMC5507920 | biostudies-literature
Project description:IntroductionA vaccine against influenza is available seasonally but is not 100% effective. A predictor of successful seroconversion in adults is an increase in activated circulating T follicular helper (cTfh) cells after vaccination. However, the impact of repeated annual vaccinations on long-term protection and seasonal vaccine efficacy remains unclear.MethodsIn this study, we examined the T cell receptor (TCR) repertoire and transcriptional profile of vaccine-induced expanded cTfh cells in individuals who received sequential seasonal influenza vaccines. We measured the magnitude of cTfh and plasmablast cell activation from day 0 (d0) to d7 post-vaccination as an indicator of a vaccine response. To assess TCR diversity and T cell expansion we sorted activated and resting cTfh cells at d0 and d7 post-vaccination and performed TCR sequencing. We also single cell sorted activated and resting cTfh cells for TCR analysis and transcriptome sequencing.Results and discussionThe percent of activated cTfh cells significantly increased from d0 to d7 in each of the 2016-17 (p < 0.0001) and 2017-18 (p = 0.015) vaccine seasons with the magnitude of cTfh activation increase positively correlated with the frequency of circulating plasmablast cells in the 2016-17 (p = 0.0001) and 2017-18 (p = 0.003) seasons. At d7 post-vaccination, higher magnitudes of cTfh activation were associated with increased clonality of cTfh TCR repertoire. The TCRs from vaccine-expanded clonotypes were identified and tracked longitudinally with several TCRs found to be present in both years. The transcriptomic profile of these expanded cTfh cells at the single cell level demonstrated overrepresentation of transcripts of genes involved in the type-I interferon pathway, pathways involved in gene expression, and antigen presentation and recognition. These results identify the expansion and transcriptomic profile of vaccine-induced cTfh cells important for B cell help.
| S-EPMC10095155 | biostudies-literature
Project description:BackgroundInfluenza has long burdened the Military Health System (MHS). This study assesses the impact of repeated annual vaccination on influenza vaccine effectiveness (VE).MethodsThis retrospective, case control study using the test-negative design utilized data extracted from the MHS Data Repository (MDR). Cases had a positive influenza test and controls sought care for an influenza-like illness within 2 weeks of a case, had no positive influenza tests, and were matched by sex, race, age, and location. Vaccine effectiveness was assessed using conditional logistic regression separately for those who received inactivated and live attenuated influenza vaccines (LAIV).ResultsA total of 6860 cases and controls were identified in the MDR, among whom 53% were vaccinated in all 3 seasons. Among those who received inactivated influenza vaccine during the current season, VE ranged from 26% to 37% (2012/13 [A(H3N2)]: VE 26%, 95% confidence interval [CI] = 1%-45%; 2013/14 [A(H1N1)pdm09]: VE 37%, 95% CI = 18%-52%; 2014/15 [A(H3N2)]: VE 31%, 95% CI = 17%-42%). The VE ranged from 25% to 49% for those only vaccinated this season (2012/13 [A(H3N2)]: VE 38%, 95% CI = -3% to 63%; 2013/14 [A(H1N1)pdm09]: VE 49%, 95% CI = 11%-71%; 2014/15 [A(H3N2)]: VE 25%, 95% CI = -7% to 48%). The VE was more variable in those who received LAIV in the current season. No statistically significant differences in VE were observed between those frequently vaccinated and those vaccinated only during the current season.ConclusionsThese results underscore the value of annual influenza vaccinations for preventing infection while highlighting the need for continued improvements in influenza vaccine effectiveness.
| S-EPMC9578161 | biostudies-literature
Project description:BACKGROUND:Longitudinal evidence on change of serum urate level with mortality risk is limited as prior studies have a measurement of serum urate at a single time point. Further, the combined effect of serum urate and systemic inflammation on mortality is unknown. METHODS:We conducted a prospective cohort study of 152,358 participants (122,045 men and 30,313 women) with repeated measurements of serum urate in 2006, 2008, 2010, and 2012 (107,751 participants had all four measurements of serum urate). We used the Cox proportional hazard model to examine the association between cumulative average and changes in serum urate with mortality. The combined effect of serum urate and systemic inflammation was determined by testing the interaction of serum urate and high-sensitive C-reactive protein (hs-CRP) in relation to mortality risk. RESULTS:During a median follow-up of 8.7 (interquartile range 6.3-9.2) years, we identified 7564 all-cause deaths, 1763 CVD deaths, 1706 cancer deaths, and 1572 other deaths. We observed U-shaped relationships of cumulative average serum urate with all-cause mortality, cardiovascular mortality, and other mortalities. Compared with participants with stable serum urate, those with greater increases in serum urate had a 1.7-fold elevated mortality (hazard ratio (HR) = 1.66, 95% confidence interval (CI) = 1.49-1.84), and those with decreased serum urate had a 2-fold elevated mortality risk (HR = 2.14, 95% CI 1.93-2.37). Participants with both hyperuricemia and hs-CRP had 1.6 times higher mortality, compared with those with low serum urate and hs-CRP levels (HR = 1.56, 95% CI 1.37-1.76). CONCLUSIONS:We observed a U-shaped relationship of long-term cumulative average serum urate with all-cause mortality, cardiovascular mortality, and other mortalities. Compared with participants with relatively stable serum urate levels, a greater increase or decrease in serum urate was associated with elevated mortality. Participants with both hyperuricemia and high systemic inflammation had the greatest mortality risk compared with those with low serum urate and low hs-CRP levels.
| S-EPMC7160947 | biostudies-literature
Project description:Molecular Features of the Serological IgG Repertoire Elicited by Egg-based, Cell-based, or Recombinant HA Seasonal Influenza Vaccines. __sample information__ Donorname day0S1 or day28S2 Elu or FT Pf number A1 S1 FT 7649_JL_5a.raw A1 S1 FT 7649_JL_5b.raw A1 S1 FT 7649_JL_5c.raw A1 S2 FT 7649_JL_7a.raw A1 S2 FT 7649_JL_7b.raw A1 S2 FT 7649_JL_7c.raw A1 S1 Elu 7649_JL_6a.raw A1 S1 Elu 7649_JL_6b.raw A1 S1 Elu 7649_JL_6c.raw A1 S2 Elu 7649_JL_8a.raw A1 S2 Elu 7649_JL_8b.raw A1 S2 Elu 7649_JL_8c.raw A2 S1 FT 8078_JP_1a.raw A2 S1 FT 8078_JP_1b.raw A2 S1 FT 8078_JP_1c.raw A2 S2 FT 8078_JP_2a.raw A2 S2 FT 8078_JP_2b.raw A2 S2 FT 8078_JP_2c.raw A2 S1 Elu 8078_JP_3a.raw A2 S1 Elu 8078_JP_3b.raw A2 S1 Elu 8078_JP_3c.raw A2 S2 Elu 8078_JP_4a.raw A2 S2 Elu 8078_JP_4b.raw A2 S2 Elu 8078_JP_4c.raw A3 S1 FT 8116_JP_1a.raw A3 S1 FT 8116_JP_1b.raw A3 S1 FT 8116_JP_1c.raw A3 S2 FT 8116_JP_2a.raw A3 S2 FT 8116_JP_2b.raw A3 S2 FT 8116_JP_2c.raw A3 S1 Elu 8116_JP_3a.raw A3 S1 Elu 8116_JP_3b.raw A3 S1 Elu 8116_JP_3c.raw A3 S2 Elu 8116_JP_4a.raw A3 S2 Elu 8116_JP_4b.raw A3 S2 Elu 8116_JP_4c.raw A4 S1 FT 8149_JP_1a.raw A4 S1 FT 8149_JP_1b.raw A4 S1 FT 8149_JP_1c.raw A4 S2 FT 8149_JP_2a.raw A4 S2 FT 8149_JP_2b.raw A4 S2 FT 8149_JP_2c.raw A4 S1 Elu 8149_JP_3a.raw A4 S1 Elu 8149_JP_3b.raw A4 S1 Elu 8149_JP_3c.raw A4 S2 Elu 8149_JP_4a.raw A4 S2 Elu 8149_JP_4b.raw A4 S2 Elu 8149_JP_4c.raw A5 S1 FT 8209_JP_1a.raw A5 S1 FT 8209_JP_1b.raw A5 S1 FT 8209_JP_1c.raw A5 S2 FT 8209_JP_2a.raw A5 S2 FT 8209_JP_2b.raw A5 S2 FT 8209_JP_2c.raw A5 S1 Elu 8209_JP_3a.raw A5 S1 Elu 8209_JP_3b.raw A5 S1 Elu 8209_JP_3c.raw A5 S2 Elu 8209_JP_4a.raw A5 S2 Elu 8209_JP_4b.raw A5 S2 Elu 8209_JP_4c.raw B1 S1 FT 7924_JL_1a.raw B1 S1 FT 7924_JL_1b.raw B1 S1 FT 7924_JL_1c.raw B1 S2 FT 7924_JL_2a.raw B1 S2 FT 7924_JL_2b.raw B1 S2 FT 7924_JL_2c.raw B1 S1 Elu 7924_JL_4a.raw B1 S1 Elu 7924_JL_4b.raw B1 S1 Elu 7924_JL_4c.raw B1 S2 Elu 7924_JL_5a.raw B1 S2 Elu 7924_JL_5b.raw B1 S2 Elu 7924_JL_5c.raw B2 S1 FT 7947_JL_1a.raw B2 S1 FT 7947_JL_1b.raw B2 S1 FT 7947_JL_1c.raw B2 S2 FT 7947_JL_2a.raw B2 S2 FT 7947_JL_2b.raw B2 S2 FT 7947_JL_2c.raw B2 S1 Elu 7947_JL_3a.raw B2 S1 Elu 7947_JL_3b.raw B2 S1 Elu 7947_JL_3c.raw B2 S2 Elu 7947_JL_4a.raw B2 S2 Elu 7947_JL_4b.raw B2 S2 Elu 7947_JL_4c.raw B3 S1 FT 8129_JL_1a.raw B3 S1 FT 8129_JL_1b.raw B3 S1 FT 8129_JL_1c.raw B3 S2 FT 8129_JL_2a.raw B3 S2 FT 8129_JL_2b.raw B3 S2 FT 8129_JL_2c.raw B3 S1 Elu 8129_JL_3a.raw B3 S1 Elu 8129_JL_3b.raw B3 S1 Elu 8129_JL_3c.raw B3 S2 Elu 8129_JL_4a.raw B3 S2 Elu 8129_JL_4b.raw B3 S2 Elu 8129_JL_4c.raw B4 S1 FT 8164_JP_1a.raw B4 S1 FT 8164_JP_1b.raw B4 S1 FT 8164_JP_1c.raw B4 S2 FT 8164_JP_2a.raw B4 S2 FT 8164_JP_2b.raw B4 S2 FT 8164_JP_2c.raw B4 S1 Elu 8164_JP_3a.raw B4 S1 Elu 8164_JP_3b.raw B4 S1 Elu 8164_JP_3c.raw B4 S2 Elu 8164_JP_4a.raw B4 S2 Elu 8164_JP_4b.raw B4 S2 Elu 8164_JP_4c.raw B5 S1 FT 8237_JP_1a.raw B5 S1 FT 8237_JP_1b.raw B5 S1 FT 8237_JP_1c.raw B5 S2 FT 8237_JP_2a.raw B5 S2 FT 8237_JP_2b.raw B5 S2 FT 8237_JP_2c.raw B5 S1 Elu 8237_JP_3a.raw B5 S1 Elu 8237_JP_3b.raw B5 S1 Elu 8237_JP_3c.raw B5 S2 Elu 8237_JP_4a.raw B5 S2 Elu 8237_JP_4b.raw B5 S2 Elu 8237_JP_4c.raw C1 S1 FT 8108_JP_1a.raw C1 S1 FT 8108_JP_1b.raw C1 S1 FT 8108_JP_1c.raw C1 S2 FT 8108_JP_2a.raw C1 S2 FT 8108_JP_2b.raw C1 S2 FT 8108_JP_2c.raw C1 S1 Elu 8108_JP_3a.raw C1 S1 Elu 8108_JP_3b.raw C1 S1 Elu 8108_JP_3c.raw C1 S2 Elu 8108_JP_4a.raw C1 S2 Elu 8108_JP_4b.raw C1 S2 Elu 8108_JP_4c.raw C2 S1 FT 8048_JL_1a.raw C2 S1 FT 8048_JL_1b.raw C2 S1 FT 8048_JL_1c.raw C2 S2 FT 8048_JL_2a.raw C2 S2 FT 8048_JL_2b.raw C2 S2 FT 8048_JL_2c.raw C2 S1 Elu 8048_JL_3a.raw C2 S1 Elu 8048_JL_3b.raw C2 S1 Elu 8048_JL_3c.raw C2 S2 Elu 8048_JL_4a.raw C2 S2 Elu 8048_JL_4b.raw C2 S2 Elu 8048_JL_4c.raw C3 S1 FT 8068_JP_1a.raw C3 S1 FT 8068_JP_1b.raw C3 S1 FT 8068_JP_1c.raw C3 S2 FT 8068_JP_2a.raw C3 S2 FT 8068_JP_2b.raw C3 S2 FT 8068_JP_2c.raw C3 S1 Elu 8068_JP_3a.raw C3 S1 Elu 8068_JP_3b.raw C3 S1 Elu 8068_JP_3c.raw C3 S2 Elu 8108_JP_5a.raw C3 S2 Elu 8108_JP_5b.raw C3 S2 Elu 8108_JP_5c.raw C4 S1 FT 8203_JP_1a.raw C4 S1 FT 8203_JP_1b.raw C4 S1 FT 8203_JP_1c.raw C4 S2 FT 8203_JP_2a.raw C4 S2 FT 8203_JP_2b.raw C4 S2 FT 8203_JP_2c.raw C4 S1 Elu 8203_JP_3a.raw C4 S1 Elu 8203_JP_3b.raw C4 S1 Elu 8203_JP_3c.raw C4 S2 Elu 8203_JP_4a.raw C4 S2 Elu 8203_JP_4b.raw C4 S2 Elu 8203_JP_4c.raw C5 S1 FT 8258_JP_1a.raw C5 S1 FT 8258_JP_1b.raw C5 S1 FT 8258_JP_1c.raw C5 S2 FT 8258_JP_2a.raw C5 S2 FT 8258_JP_2b.raw C5 S2 FT 8258_JP_2c.raw C5 S1 Elu 8258_JP_3a.raw C5 S1 Elu 8258_JP_3b.raw C5 S1 Elu 8258_JP_3c.raw C5 S2 Elu 8258_JP_4a.raw C5 S2 Elu 8258_JP_4b.raw C5 S2 Elu 8258_JP_4c.raw
2025-01-15 | PXD046473 | Pride
Project description:Antibodies to influenza surface protein neuraminidase (NA) have been found to reduce disease severity and may be an independent correlate of protection. Despite this, current influenza vaccines have no regulatory requirements for the quality or quantity of the NA antigen and are not optimized for induction of NA-specific antibodies. Here we investigate the induction and durability of NA-specific antibody titers after pandemic AS03-adjuvanted monovalent H1N1 vaccination and subsequent annual vaccination in health care workers in a five-year longitudinal study. NA-specific antibodies were measured by endpoint ELISA and functional antibodies measured by enzyme-linked lectin assay (ELLA) and plaque reduction naturalisation assay. We found robust induction of NA inhibition (NAI) titers with a 53% seroconversion rate (>4-fold) after pandemic vaccination in 2009. Furthermore, the endpoint and NAI geometric mean titers persisted above pre-vaccination levels up to five years after vaccination in HCWs that only received the pandemic vaccine, which demonstrates considerable durability. Vaccination with non-adjuvanted trivalent influenza vaccines (TIV) in subsequent influenza seasons 2010/2011 - 2013/2014 further boosted NA-specific antibody responses. We found that each subsequent vaccination increased durable endpoint titers and contributed to maintaining the durability of functional antibody titers. Although the trivalent influenza vaccines boosted NA-specific antibodies, the magnitude of fold-increase at day 21 declined with repeated vaccination, particularly for functional antibody titers. High levels of pre-existing antibodies were associated with lower fold-induction in repeatedly vaccinated HCWs. In summary, our results show that durable NA-specific antibody responses can be induced by an adjuvanted influenza vaccine, which can be maintained and further boosted by TIVs. Although NA-specific antibody responses are boosted by annual influenza vaccines, high pre-existing titers may negatively affect the magnitude of fold-increase in repeatedly vaccinated individuals. Our results support continued development and standardization of the NA antigen to supplement current influenza vaccines and reduce the burden of morbidity and mortality.
| S-EPMC8551669 | biostudies-literature
Project description:The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we have developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes via a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately one month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals, and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year-although the titers six months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. This study demonstrates the utility of high-throughput sequencing-based neutralization assays that enable titers to be simultaneously measured against many different viral strains. We provide a detailed experimental protocol (DOI: https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1) and a computational pipeline (https://github.com/jbloomlab/seqneut-pipeline) for the sequencing-based neutralization assays to facilitate the use of this method by others.
| S-EPMC10942427 | biostudies-literature
Project description:Annual seasonal influenza vaccination is recommended for high-risk populations and often occupational groups such as healthcare workers (HCWs). Repeated annual vaccination has been reported to either have no impact or reduce antibody responses or protection. However, whether repeated vaccination influences T-cell responses has not been sufficiently studied, despite the increasing evidence of the protective roles of T-cell immunity. Here, we explored the impact of repeated annual vaccination with the same vaccine strain (H1N1pdm09) over multiple seasons in the post-2009 pandemic era and showed that repeated vaccination increased both T-cell and humoral responses. Using the T-cell FluroSpot and intracellular cytokine-staining, the hemagglutination inhibition (HI), and the memory B-cell (MBC) ELISpot assays, we investigated pre- and postvaccination T cells, antibodies, and MBCs in a cohort of HCWs repeatedly vaccinated with H1N1pdm09 for 5 years (pandemic vaccination in 2009 and subsequently annual seasonal vaccination containing H1N1pdm09 during 2010-2013). We found that the prevaccination H1N1pdm09-specific T cells, antibodies, and MBCs were significantly increased after 3-4 repeated vaccinations and maintained at high levels throughout seasons 2012 and 2013. The cross-reactive IFN-?-secreting CD4+ cells recognizing conserved viral external or internal epitopes were also maintained throughout 2012 and 2013. Repeated vaccination improved the multifunctional memory CD4+ responses. Particularly, the IFN-?+TNF-?+CD4+ T cells were boosted following each vaccination. HI antibodies were significantly induced after each vaccination over 5 years. Our findings indicate a broad impact of repeated annual vaccination, even with the same vaccine component, on the influenza-specific T-cell and humoral immunity and support the continuing recommendation of annual influenza vaccination. Despite the widespread implementation of annual influenza vaccination, the effect of repeated vaccinations on the immune response in subsequent seasons is poorly understood. A team led by Rebecca Jane Cox at the University of Bergen examined the humoral and T-cell response elicited by 2009's H1N1pdm09 seasonal vaccine. Since the H1N1pdm09 strain continued to circulate in subsequent years it was included in later vaccine formulations and the authors could therefore examine the effects of repeated annual vaccination over multiple seasons. They observed that H1N1pdm09-specific polyfunctional T-cell responses and antibodies were enhanced by multiple annual vaccinations. In particular, T cells showed progressive skewing to IFN-?+TNF+ double producers, but the magnitude of the T-cell response tended to plateau after 3-4 repeated vaccinations. The findings suggest that including the same component in subsequent annual vaccines can significantly impact the influenza immune response.
| S-EPMC6092382 | biostudies-literature