scholarly journals Preexisting Immunity, More Than Aging, Influences Influenza Vaccine Responses

2015 ◽  
Vol 2 (2) ◽  
Author(s):  
Adrian J. Reber ◽  
Jin Hyang Kim ◽  
Renata Biber ◽  
H. Keipp Talbot ◽  
Laura A. Coleman ◽  
...  
Keyword(s):  
Older Adults ◽  
B Cells ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Hemagglutination Inhibition ◽  
Negative Impact ◽  
Memory B Cells ◽  
Vaccine Response ◽  
Vaccine Responses ◽  
Antibody Levels

Abstract Background.  Influenza disproportionately impacts older adults while current vaccines have reduced effectiveness in the older population. Methods.  We conducted a comprehensive evaluation of cellular and humoral immune responses of adults aged 50 years and older to the 2008–2009 seasonal trivalent inactivated influenza vaccine and assessed factors influencing vaccine response. Results.  Vaccination increased hemagglutination inhibition and neutralizing antibody; however, 66.3% of subjects did not reach hemagglutination inhibition titers ≥ 40 for H1N1, compared with 22.5% for H3N2. Increasing age had a minor negative impact on antibody responses, whereas prevaccination titers were the best predictors of postvaccination antibody levels. Preexisting memory B cells declined with age, especially for H3N2. However, older adults still demonstrated a significant increase in antigen-specific IgG+ and IgA+ memory B cells postvaccination. Despite reduced frequency of preexisting memory B cells associated with advanced age, fold-rise in memory B cell frequency in subjects 60+ was comparable to subjects age 50–59. Conclusions.  Older adults mounted statistically significant humoral and cell-mediated immune responses, but many failed to reach hemagglutination inhibition titers ≥40, especially for H1N1. Although age had a modest negative effect on vaccine responses, prevaccination titers were the best predictor of postvaccination antibody levels, irrespective of age.

scholarly journals Preexisting Immunity, Not Frailty Phenotype, Predicts Influenza Postvaccination Titers among Older Veterans

2017 ◽  
Vol 24 (3) ◽  
Author(s):  
Puja Van Epps ◽  
Terrence Tumpey ◽  
Melissa B. Pearce ◽  
Hana Golding ◽  
Patricia Higgins ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Functional Impairment ◽  
Influenza B ◽  
Strongly Correlated ◽  
Frailty Phenotype ◽  
Vaccine Responses ◽  
Frailty Status ◽  
Age Range

ABSTRACT Both preexisting immunity to influenza and age have been shown to be correlates of influenza vaccine responses. Frailty, an indicator of functional impairment in older adults, was also shown in one study to predict lower influenza vaccine responses among nonveterans. In the current study, we aimed to determine the associations between frailty, preexisting immunity, and immune responses to influenza vaccine among older veterans. We studied 117 subjects (age range, 62 to 95 years [median age, 81 years]), divided into three cohorts based on the Fried frailty test, i.e., nonfrail (NF) (n = 23 [median age, 68 years]), prefrail (n = 50 [median age, 80 years]), and frail (n = 44 [median age, 82 years]), during the 2010-2011 and 2011-2012 influenza seasons. Subjects received the seasonal trivalent inactivated influenza vaccine, and baseline and postvaccination samples were obtained. Anti-influenza humoral immunity, as measured by hemagglutination inhibition (HI) and microneutralization assays, was measured for influenza B, A(H1N1)pdm09, and A(H3N2) viruses. Postvaccination titers were not different between frail and NF subjects overall in this older subset of veterans. However, preexisting HI titers were strongly correlated with postvaccination titers among all functional status groups. When microneutralization titers were compared, the association between preexisting immunity and vaccine responses varied by frailty status, with the strongest correlation being observed for the NF group. In conclusion, preexisting immunity rather than frailty appeared to predict postvaccination titers in this older veteran cohort.

scholarly journals High Preexisting Serological Antibody Levels Correlate with Diversification of the Influenza Vaccine Response

2015 ◽  
Vol 89 (6) ◽  
pp. 3308-3317 ◽  
Author(s):  
Sarah F. Andrews ◽  
Kaval Kaur ◽  
Noel T. Pauli ◽  
Min Huang ◽  
Yunping Huang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
B Cells ◽  
Influenza Vaccine ◽  
B Cell ◽  
Cell Response ◽  
Vaccine Response ◽  
Trivalent Influenza Vaccine ◽  
Antibody Levels ◽  
Virus Strains ◽  
B Cell Response

ABSTRACTReactivation of memory B cells allows for a rapid and robust immune response upon challenge with the same antigen. Variant influenza virus strains generated through antigenic shift or drift are encountered multiple times over the lifetime of an individual. One might predict, then, that upon vaccination with the trivalent influenza vaccine across multiple years, the antibody response would become more and more dominant toward strains consistently present in the vaccine at the expense of more divergent strains. However, when we analyzed the vaccine-induced plasmablast, memory, and serological responses to the trivalent influenza vaccine between 2006 and 2013, we found that the B cell response was most robust against more divergent strains. Overall, the antibody response was highest when one or more strains contained in the vaccine varied from year to year. This suggests that in the broader immunological context of viral antigen exposure, the B cell response to variant influenza virus strains is not dictated by the composition of the memory B cell precursor pool. The outcome is instead a diversified B cell response.IMPORTANCEVaccine strategies are being designed to boost broadly reactive B cells present in the memory repertoire to provide universal protection to the influenza virus. It is important to understand how past exposure to influenza virus strains affects the response to subsequent immunizations. The viral epitopes targeted by B cells responding to the vaccine may be a direct reflection of the B cell memory specificities abundant in the preexisting immune repertoire, or other factors may influence the vaccine response. Here, we demonstrate that high preexisting serological antibody levels to a given influenza virus strain correlate with low production of antibody-secreting cells and memory B cells recognizing that strain upon revaccination. In contrast, introduction of antigenically novel strains generates a robust B cell response. Thus, both the preexisting memory B cell repertoire and serological antibody levels must be taken into consideration in predicting the quality of the B cell response to new prime-boost vaccine strategies.

scholarly journals Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e040426
Author(s):  
Gyaviira Nkurunungi ◽  
Ludoviko Zirimenya ◽  
Jacent Nassuuna ◽  
Agnes Natukunda ◽  
Prossy N Kabuubi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Low Income ◽  
Controlled Trial ◽  
Interferon Γ ◽  
Population Differences ◽  
Vaccine Response ◽  
Vaccine Responses ◽  
Helminth Infections ◽  
Registration Number ◽  
Randomised Controlled

IntroductionSeveral licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response.Methods and analysisWe have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9–17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day ‘zero’; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses.Ethics and disseminationEthics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration numberISRCTN60517191.

scholarly journals Determinants of Protection Against Measles Infection in a Vaccinated Healthcare Worker

2020 ◽  
Vol 41 (S1) ◽  
pp. s185-s185
Author(s):  
Annie St-Pierre ◽  
Anne-Marie Charron ◽  
Pamela Doyon-Plourde ◽  
Caroline Quach
Keyword(s):  
Vaccination Status ◽  
Secondary Case ◽  
Enzyme Linked Immunosorbent Assay ◽  
Demographic Information ◽  
Vaccine Response ◽  
Vaccine Responses ◽  
Equivocal Result ◽  
Commercial Enzyme Immunoassay ◽  
Antibody Levels ◽  
Care Worker

Background: In 2019, a measles community outbreak resulted in a secondary case in a health care worker (HCW) working in a pediatric hospital in Montral, Canada. Following the event, HCWs were screened to identify individuals susceptible to measles infection based on serology results. Objective: Our aim was to assess measles seroprotection rates and to evaluate vaccine responses of susceptible HCWs using commercial enzyme immunoassay (EIA) or enzyme linked immunosorbent assay (ELISA). Methods: Emergency department (ED) employees, including doctors, were screened for measles susceptibility as part of a postoutbreak measure by the hospital occupational health service. Demographic information was collected. Measles history and vaccination information were collected using a personal vaccination booklet, employee vaccination profile, or the Qubec vaccination registry. According to the Quebec Immunization Protocol (PIQ), individuals born before 1970, or who have received 2 doses of a measles-containing vaccines are considered protected. Individuals with undetectable or equivocal antibody levels were considered at risk of measles infection. These individuals were offered vaccination and were tested for vaccine response 4 weeks after vaccination. Results: Anti-IgG measles antibody results, demographic information, and vaccination information were obtained for 257 employees. The results are currently available for 233 HCWs: 224 HCWs (96%) were seropositive, 7 (3%) were seronegative, and 2 were equivocal. Among seronegative individuals, 6 (85.7%) were born after 1980 and 3 (42.9%) had received 2 doses of a measles-containing vaccine. Of those with an equivocal result, 1 (50%) had received 2 doses and 1 (50%), born after 1970, did not confirm vaccination status. Finally, 9 (4%) of seropositive individuals were not vaccinated; of whom 8 (88.9%) were born before 1970. Conclusions: Our preliminary results suggest that the 95% immunity threshold that is usually required to prevent secondary transmission of measles has been reached in our ED HCW cohort. Even years after the second MMR dose, HCWs remain well protected. Relying on documented vaccination status is thus acceptable.Funding: NoneDisclosures: None

scholarly journals Induction of long-lived germinal centers associated with persisting antigen after viral infection.

1996 ◽  
Vol 183 (5) ◽  
pp. 2259-2269 ◽  
Author(s):  
M F Bachmann ◽  
B Odermatt ◽  
H Hengartner ◽  
R M Zinkernagel
Keyword(s):  
T Cell ◽  
B Cells ◽  
Viral Infection ◽  
Neutralizing Antibody ◽  
Germinal Centers ◽  
Memory B Cells ◽  
Specific Memory ◽  
Specific Amplification ◽  
Antibody Levels ◽  
Red Pulp

Vesicular stomatitis virus (VSV) induces an early T cell-independent neutralizing lgM response that is followed by a long-lived, T cell-dependent lgG response. We used the specific amplification factor of several 100x of VSV-virions for immunohistology to analyze the localization of VSV-specific B cells at different time points after immunization. At the peak of the IgM response (day 4), VSV-specific B cells were predominantly present in the red pulp and marginal zone but not in the T area. These B cells were mostly stained in the cytoplasm, characterizing them as antibody secreting cells. By day 6 after immunization, germinal centers (GC) containing surface-stained VSV-specific B cells became detectable and were fully established by day 12. At the same time, large VSV-specific B cell aggregates were present in the red pulp. High numbers of VSV-specific GC associated with persisting antigen were present 1 mo after immunization and later, i.e., considerably longer than has been observed for haptens. Some GC, exhibiting follicular dendritic cells and containing VSV-specific, proliferating B cells were still detectable up to 100 d after immunization. Long-lived GC were also observed after immunization with recombinant VSV-glycoprotein in absence of adjuvants. Thus some anti-virally protective (memory) B cells are cycling and locally proliferate in long-lived GC in association with persisting antigen and therefore seem responsible for long-term maintenance of elevated antibody levels. These observations extend earlier studies with carrier hapten antigens in adjuvant depots or complexed with specific IgG; they are the first to show colocalization of antigen and specific memory B cells and to analyze a protective neutralizing antibody response against an acute viral infection.

scholarly journals T-independent antigen induces humoral memory through germinal centers

2022 ◽  
Vol 219 (3) ◽  
Author(s):  
Xin Liu ◽  
Yongshan Zhao ◽  
Hai Qi
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Germinal Center ◽  
Plasma Cells ◽  
Underlying Mechanism ◽  
Memory B Cells ◽  
Antigen B ◽  
Per Se ◽  
Humoral Responses ◽  
Human And Mouse

T-dependent humoral responses generate long-lived memory B cells and plasma cells (PCs) predominantly through germinal center (GC) reaction. In human and mouse, memory B cells and long-lived PCs are also generated during immune responses to T-independent antigen, including bacterial polysaccharides, although the underlying mechanism for such T-independent humoral memory is not clear. While T-independent antigen can induce GCs, they are transient and thought to be nonproductive. Unexpectedly, by genetic fate-mapping, we find that these GCs actually output memory B cells and PCs. Using a conditional BCL6 deletion approach, we show memory B cells and PCs fail to last when T-independent GCs are precluded, suggesting that the GC experience per se is important for programming longevity of T-independent memory B cells and PCs. Consistent with the fact that infants cannot mount long-lived humoral memory to T-independent antigen, B cells from young animals intrinsically fail to form T-independent GCs. Our results suggest that T-independent GCs support humoral memory, and GC induction may be key to effective vaccines with T-independent antigen.

scholarly journals Memory B cells: Effectors of long-lived immune responses

2009 ◽  
Vol 39 (8) ◽  
pp. 2065-2075 ◽  
Author(s):  
Stuart G. Tangye ◽  
David M. Tarlinton
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Memory B Cells

The Effect of Influenza Vaccination History on Changes in Hemagglutination Inhibition Titers After Receipt of the 2015–2016 Influenza Vaccine in Older Adults in Hong Kong

2019 ◽  
Vol 221 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Tiffany W Y Ng ◽  
Ranawaka A P M Perera ◽  
Vicky J Fang ◽  
Emily M Yau ◽  
J S Malik Peiris ◽  
...  
Keyword(s):  
Older Adults ◽  
Hong Kong ◽  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Hemagglutination Inhibition ◽  
Age Groups ◽  
Antibody Responses ◽  
Serum Samples ◽  
Vaccination History ◽  
Antibody Titers

Abstract Background Immune responses to influenza vaccination can be weaker in older adults than in other age groups. We hypothesized that antibody responses would be particularly weak among repeat vaccinees when the current and prior season vaccine components are the same. Methods An observational study was conducted among 827 older adults (aged ≥75 years) in Hong Kong. Serum samples were collected immediately before and 1 month after receipt of the 2015–2016 quadrivalent inactivated influenza vaccine. We measured antibody titers with the hemagglutination inhibition assay and compared the mean fold rise from prevaccination to postvaccination titers and the proportions with postvaccination titers ≥40 or ≥160. Results Participants who reported receipt of vaccination during either of the previous 2 years had a lower mean fold rise against all strains than with those who did not. Mean fold rises for A(H3N2) and B/Yamagata were particularly weak after repeated vaccination with the same vaccine strain, but we did not generally find significant differences in the proportions of participants with postvaccination titers ≥40 and ≥160. Conclusions Overall, we found that reduced antibody responses in repeat vaccinees were particularly reduced among older adults who had received vaccination against the same strains in preceding years.

scholarly journals Effects of Prior Influenza Exposure on Immunogenicity of Influenza Vaccine

2020 ◽  
Author(s):  
Jia-Qian Cao ◽  
Peng-Fei Jin ◽  
Zhao-Zhun Zeng ◽  
Li Zhang ◽  
Fan-Yue Meng ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Influenza Virus ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Hemagglutination Inhibition ◽  
Cross Reactivity ◽  
Vaccine Effectiveness ◽  
Prior Exposure ◽  
Post Vaccination ◽  
Blood Samples

Abstract Background To investigate effects of prior influenza exposure on vaccine-elicited humor immune responses to circulating influenza variants. Method We randomly selected 360 participants in previous clinical trials stratified by age. Blood samples before and 28 days after vaccination were collected and tested by hemagglutination-inhibition tests against both vaccine strains and circulating variants during the 2015–2016 influenza seasons in China. The antigenic map was plotted and antigenic distance was calculated. Results Subjects with H1-priming had higher cross-reactive antibodies titers against A/JiangsuTinghu/11019/2015(H3N2) compared with subjects with B-priming did (Padjusted=0.038). Subjects with H1-priming also had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming did (Padjusted=0.036). Nevertheless, subjects with no H1 and B-priming had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming did (Padjusted=0.012). Antigenic distance was well-matched with serological results. Besides, age-specific differences in human post-vaccination responses against the identical circulating strain was noted. And children had most cross-reactive response to both H3N2 and B-yamagata subtypes. Conclusion Our results suggest that prior exposure to H1 or B influenza virus may influence cross-reactivity of H3-specific post-vaccination responses and consequently could influence the vaccine effectiveness. Our findings also support that there are age-specific differences in human post-vaccination responses.

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