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

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. ### Competing Interest Statement Thierry Ollinger and Wivine Burny are employees of the GSK group of companies. Wivine Burny holds shares in the GSK group of companies. All other authors have no conflict of interest. ### Clinical Trial EudraCT: 2019-000836-24, NL69701.041.19 ### Funding Statement The VITAL project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 806776 and the Dutch Ministry of Health, Welfare and Sport. The JU receives support from the European Union's Horizon 2020 research and innovation program and EFPIA‐members. The VITAL- Corona study was funded by the Dutch Ministry of Health, Welfare and Sport. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained through the Medical Research Ethics Committee Utrecht (NL69701.041.19, EudraCT: 2019-000836-24). All participants provided written informed consent and all procedures were performed with Good Clinical Practice and in accordance with the principles of the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets generated during the current studies are not made available in a public database since the study is ongoing. We will share pseudonymized data upon reasonable request as long as data transfer is in agreement with the clinical protocol and EU legislation on the General Data Protection Regulation, which should be regulated in a data sharing agreement.