Influence of age, sex, body habitus, vaccine type and anti-S serostatus on cellular and humoral responses to SARS-CoV-2 vaccination

Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+ T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+ CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI associate with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by Barts Charity (grants MGU0466 to A. R. M., MGU0459 to D. A. J. and E. S. C., and MGU0558 to J. M. G. and A. M.); by the Fischer Family Trust, The Exilarchs Foundation, and DSM Nutritional Products (donations to Queen Mary University of London); the Rosetrees Trust and The Bloom Foundation (grant M771 to M. T.); the Rosetrees Trust (grant CF1 \100003 to J. M. G. and A. M.); and the John Black Charitable Foundation (grant M946 to A. M.). AKC is supported by the NHMRC (GNT2020750). ### 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: The trial was sponsored by Queen Mary University of London, approved by the Queens Square Research Ethics Committee, London, U.K. (ref 20/HRA/5095) and registered with ClinicalTrials.gov ([NCT04579640][1]) on 8 October 2020, before enrolment of the first participant on 28 October 2020. 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 All data produced in the present work are contained in the manuscript [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04579640&atom=%2Fmedrxiv%2Fearly%2F2023%2F09%2F29%2F2023.09.29.23296222.atom