# Age differences in immunity to human seasonal coronaviruses and the immunogenicity of ChAdOx1 nCoV-19 (AZD1222)

## TL;DR

Younger people had stronger immune responses to the ChAdOx1 nCoV-19 vaccine compared to older people, possibly due to prior immunity to seasonal coronaviruses.

## Contribution

The study reveals age-related differences in vaccine immunogenicity linked to pre-existing immunity to seasonal coronaviruses.

## Key findings

- Younger individuals showed higher SARS-CoV-2 antibody levels, avidity, and FcγR binding after the first vaccine dose.
- Baseline immunity to seasonal coronaviruses varied geographically but showed consistent age-related trends in immune response.
- Immune differences between age groups decreased after the second vaccine dose.

## Abstract

ChAdOx1 nCoV-19 (AZD1222) vaccine was widely deployed to protect against severe COVID-19 in adults, but the relationship between pre-existing immunity to human seasonal coronaviruses (HCoVs) and vaccine-induced SARS-CoV-2 (SCoV2) response across age groups remains unclear.

We analysed SCoV2 and HCoVs antibody profiles in UK volunteers (aged 6–≥70), assessing antibody levels, avidity, and FcγR binding after receiving one or two doses of ChAdOx1 nCoV-19. Adult cohorts from trials in Brazil and Kenya were also included to evaluate geographical impacts on baseline HCoVs and SCoV2 induced response.

In the UK cohort, younger individuals had higher SCoV2 IgG, avidity, FcγR binding and cross-reactivity, particularly towards OC43 and HKU1. The greatest differences were seen after the first dose of ChAdOx1 nCoV-19, but these effects diminished after the second dose. Although baseline HCoVs IgG varied geographically, similar trends were observed across adult cohorts with younger adults showing higher SCoV2 IgG compared to older adults (UK and Brazil).

These findings contribute to a better understanding of the immunogenicity of ChAdOx1-based vaccines in various age groups. Determining whether this applies across other vaccines using same platform is essential for evaluating the viability of one-dose regimens in outbreak responses.

The clinical trials COV002, COV003, COV004, and COV006 were made possible by funding from 10.13039/100004325Astra Zeneca, the NIHR and the University of Oxford, 10.13039/501100000276UK Department of Health and Social Care, through the 10.13039/501100000272UK National Institute for Health and Care Research, the 10.13039/100010269Wellcome Trust (220991), and 10.13039/501100006041Innovate UK (project 971614).