The memory B cell response to influenza vaccination is impaired in older persons

Burton, Alice R.; Guillaume, Stephane M.; Foster, William S.; Wheatley, Adam K.; Hill, Danika L.; Carr, Edward J; Linterman, Michelle A.

doi:10.1016/j.celrep.2022.111613

Cited by 27 publications

(12 citation statements)

References 80 publications

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“…This may be due to a decline in the survival of long-lived plasma cells with advancing age and is in accordance with the general understanding of decreased survival niches for long-lived plasma cells in the ageing bone marrow 37 . Secondly, this observation is indicative of a diminished memory B cells response, potentially due to the involvement of Age Associated B (AAB) cells 38 , following vaccination in older age groups, as was also previously noted 39,40 . Therefore, booster vaccinations might be needed at older age in order to maintain long-term protection.…”

Section: Discussionsupporting

confidence: 65%

Multiple vaccine comparison in the same adults from the VITAL study reveals vaccine-specific and age-related humoral response patterns

van der Heiden,

Shetty,

Bijvank

et al. 2024

Preprint

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Vaccine responsiveness is often reduced in older adults. Yet, our lack of understanding of low vaccine responsiveness hampers the development of effective vaccination strategies to reduce the impact of infectious diseases in the ageing population. Young-adult, middle-aged and older-adult participants of the VITAL clinical trials (n=315, age range: 28-98y), were consecutively vaccinated with a booster quadrivalent influenza (QIV) vaccine, a primary 13-valent pneumococcal-conjugate (PCV13) vaccine, and a primary series of SARS-CoV2 mRNA-1273 vaccines within the timeframe of 2 years. This unique setup allowed investigation of humoral responsiveness towards multiple vaccines within the same individuals over the entire adult age-range. Booster QIV vaccination induced comparable H3N2 hemagglutination inhibition (HI) titers in all age groups, whereas primary PCV13 and mRNA-1273 vaccination induced lower antibody concentrations in older as compared to younger adults. The persistence of humoral responses towards the 6 months timepoint was shorter in older adults for all vaccines. Interestingly, the quantity of vaccine-induced humoral immunity within one individual differed between vaccines. Yet, a small group of mostly older male adults responded low to multiple vaccines. This study aids the identification of risk groups for low vaccine responsiveness and guides the design of more targeted vaccination strategies for the ageing population.

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Section: Discussionsupporting

confidence: 65%

Multiple vaccine comparison in the same adults from the VITAL study reveals vaccine-specific and age-related humoral response patterns

van der Heiden,

Shetty,

Bijvank

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…FcRL5+ B cells might exclusively react to membrane-bound antigens ( 53 , 54 ), potentially causing NC-specific FcRL5+ B cells, which respond to soluble antigens, to remain unresponsive and accumulate as FcRL5+ ActBCs in the bloodstream. Recently, FcRL5+ B cells have been depicted as recent GC graduates in one study and ASC precursors in another ( 55 , 56 ), our results suggest that differentiation in ASC and classical MBCs is accompanied by the loss of FcRL5.…”

Section: Discussionsupporting

confidence: 67%

Deep profiling of antigen-specific B cells from different pathogens identifies novel compartments in the IgG memory B cell and antibody-secreting cell lineages

Claireaux,

Elias,

Kerster

et al. 2023

Preprint

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A better understanding of the bifurcation of human B cell differentiation into memory B cells (MBC) and antibody-secreting cells (ASC) and identification of MBC and ASC precursors is crucial to optimize vaccination strategies or block undesired antibody responses. To unravel the dynamics of antigen-induced B cell responses, we compared circulating B cells reactive to SARS-CoV-2 (Spike, RBD and Nucleocapsid) in COVID-19 convalescent individuals to B cells specific to Influenza-HA, RSV-F and TT, induced much longer ago. High-dimensional spectral flow cytometry indicated that the decision point between ASC- and MBC-formation lies in the CD43+CD71+IgG+ Activated B cell compartment, showing properties indicative of recent germinal center activity and recent antigen encounter. Within this Activated B cells compartment, CD86+ B cells exhibited close phenotypical similarity with ASC, while CD86− B cells were closely related to IgG+ MBCs. Additionally, different activation stages of the IgG+ MBC compartment could be further elucidated. The expression of CD73 and CD24, regulators of survival and cellular metabolic quiescence, discerned activated MBCs from resting MBCs. Activated MBCs (CD73-CD24lo) exhibited phenotypical similarities with CD86− IgG+ Activated B cells and were restricted to SARS-CoV-2 specificities, contrasting with the resting MBC compartment (CD73-/CD24hi) that exclusively encompassed antigen-specific B cells established long ago. Overall, these findings identify novel stages for IgG+ MBC and ASC formation and bring us closer in defining the decision point for MBC or ASC differentiation.ImportanceIn this study, researchers aimed to better understand human B cell differentiation and their role in establishing long-lived humoral immunity. Using high-dimensional flow cytometry, they studied B cells reactive to three SARS-CoV-2 antigens in individuals convalescent for COVID-19, and compared their phenotypes to B cells reactive to three distinct protein antigens derived from vaccines or viruses encountered months to decades before. Their findings showed that Activated B cells reflect recent germinal center graduates that may have diverse fates; with some feeding the pool of antibody-secreting cells and others fueling the resting memory B cell compartment. Activated B cells gradually differentiate into resting memory B cells through an activated MBC phase. Increased expression of the cellular metabolic regulators CD73 and CD24 in resting memory B cells distinguishes them from the activated memory B cells phase, and is likely involved in sustaining a durable memory of humoral immunity. These findings are crucial for the development of vaccines that provide lifelong protection and may show potential to define reactive B cells in diseases where the cognate-antigen is still unknown such as in autoimmunity, cancers, or novel viral outbreaks.

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“…39 More importantly these “unconventional B cells” have been involved in influenza vaccine response 40 and their expansion has been directly linked to protective immunity after influenza vaccine in a younger cohort in comparison to an elderly cohort. 66 While increased DN B cells have been reported in other SOT cohorts 64 , we mainly observed an increase in DN B cells at baseline in patients responsive after both dose 2 and 3 of COVID-19 vaccine in our cohort ( Supplementary Figure 6A ). Moreover, activation markers such as CD86 have been reported to be decreased in SOT recipients 63,64 and it is therefore interesting to notice the best vaccine response in patients expressing a higher level of activation markers (CD80 or CD40) on their B cells.…”

Section: Discussioncontrasting

confidence: 42%

Systems vaccinology identifies clinical and immunological correlates of SARS-CoV-2 vaccine response in solid-organ transplant recipients

Gemander,

Neumann,

Veiga

et al. 2024

Preprint

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Solid organ transplant (SOT) recipients are at enhanced risk of adverse outcomes following infectious challenges due to immunosuppressive treatment and additional comorbidities. Unfortunately, SOT recipients are also poor responders to the key medical intervention to preventing infection: vaccines. Here we performed a systems vaccinology study on a cohort of 59 kidney transplant recipients and 31 lung transplant recipients who received the mRNA Pfizer-BioNTech COVID-19 vaccine. Analyzing the immunological status of the patients prior to vaccination, we were able to identify multiple immunological associates of relatively improved vaccine responses following two or three doses of mRNA-based SARS-CoV-2 vaccine. These immunological associates predicted, with 95.0% and 93.3% accuracy, vaccine response after the second and third dose, respectively. Comparison of the immunological associates with vaccine response in SOT recipients revealed two distinct immune configurations: a non-classical configuration, distinct from the immune state of healthy subjects, associated with responses to two doses of mRNA vaccine and that could be mediated partly by the presence of double negative B cell subsets which are more prominently represented in responsive SOT recipients, and a -normalized- configuration, closer to the immune state of healthy subjects, associated with potent antibody responses to three doses of mRNA vaccine. These results suggest that immunosuppression in SOT recipients can result in distinct immune states associated with different trade-offs in vaccine responsiveness. Immune phenotyping of SOT recipients for immune constellation may be an effective approach for identifying patients most at risk of poor vaccine responses and susceptibility to vaccine-preventable diseases.

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The memory B cell response to influenza vaccination is impaired in older persons

Cited by 27 publications

References 80 publications

Multiple vaccine comparison in the same adults from the VITAL study reveals vaccine-specific and age-related humoral response patterns

Multiple vaccine comparison in the same adults from the VITAL study reveals vaccine-specific and age-related humoral response patterns

Deep profiling of antigen-specific B cells from different pathogens identifies novel compartments in the IgG memory B cell and antibody-secreting cell lineages

Systems vaccinology identifies clinical and immunological correlates of SARS-CoV-2 vaccine response in solid-organ transplant recipients

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