Multiple vaccine comparison in the same adults reveals vaccine-specific and age-related humoral response patterns: an open phase IV trial

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 (25–49 y), middle-aged (50-64 y) and older-adult ( ≥ 65 y) participants of the VITAL clinical trials (n = 315, age-range: 28-98 y), were vaccinated with an annual (2019–2020) quadrivalent influenza (QIV) booster vaccine, followed by a primary 13-valent pneumococcal-conjugate (PCV13) vaccine (summer/autumn 2020) and a primary series of two SARS-CoV-2 mRNA-1273 vaccines (spring 2021). This unique setup allowed investigation of humoral responsiveness towards multiple vaccines within the same individuals over the 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 (primary endpoint). The persistence of humoral responses, towards the 6 months timepoint, was shorter in older adults for all vaccines (secondary endpoint). Interestingly, highly variable vaccine responder profiles overarching multiple vaccines were observed. Yet, approximately 10% of participants, mainly comprising of older male adults, were classified as low responders to multiple vaccines. This study aids the identification of risk groups for low vaccine responsiveness and hence supports targeted vaccination strategies. Trial number: NL69701.041.19, EudraCT: 2019-000836-24.