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.