Breadth of neutralising antibody responses to SARS-CoV-2 variants of concern is augmented by vaccination following prior infection: studies in UK healthcare workers and immunodeficient patients

Nadesalingam, A.; Cantoni, D.; Wells, D. A.; Aguinam, E. T.; Ferrari, M.; Smith, P.; Chan, A.; Carnell, G.; Ohlendorf, L.; Einhauser, S.; Wagner, R.; Temperton, N. J.; Castillo-Olivares, J. J.; Baxendale, H.; Heeney, J. L.; Consortium, Humoral immune Correlates from COVID-19

A large portion of the UK general population has currently only received a single dose of a COVID-19 vaccination (either BNT162b2 (Pfizer) or AZD1222 (Vaxevria, AstraZeneca)), making it critical that we continue to track and understand the levels of protection against SARS-CoV-2 Variants of Concern (VOCs). We undertook a single-centre cross-sectional study in order to understand the variations in vaccine-induced immunity to the SARS-CoV-2 vaccine strain (B.1) and three major VOCs (B.1.1.7, B.1351 and P.1). We studied a cohort of outpatients with immunodeficiencies (IDPs) and health care workers (HCWs) based at the same critical care tertiary NHS Trust, following a single dose of either BNT162b2 or AZD1222 vaccines. Our serological data revealed either undetectable antibodies or low neutralising antibodies (nAbs) in IDPs, with only 5% and 3% showing detectable neutralisation of B.1.1.7 and B.1.351, respectively. Healthy HCWs without a prior SARS-CoV-2 infection demonstrated a wide range of nAb titres post-vaccination. However, their responses are significantly lower than HCWs with previous SARS-CoV-2 infection. Neutralisation of VOCs with the E484K mutation (B.1.351 and P.1) were consistently lower in HCWs in the absence of evidence of prior SARS-CoV-2 infection (p<0.001). Notably, in HCWs with prior SARS-CoV-2 infection, there is a significant increase of neutralising titres post-vaccination to all four strains, compared to their pre-vaccination neutralisation titres. This underscores the importance of vaccination even in populations that have been previously exposed, and also provides support for the hypothesis that a second-dose of vaccination will similarly boost immunity to greater protective levels in individuals without prior SARS-CoV-2 exposure. Overall, this serological nAb analysis after a single-dose of BNT162b2 or AZD1222 vaccination demonstrates a wide variety of responses, particularly against the VOCs, and suggests limited neutralisation-based protection in individuals with immunodeficiencies.