The impact of prior COVID-19 on vaccine response and the resultant hybrid immunity are age-dependent

Abstract

ABSTRACTBackgroundMore people with a history of prior infection are receiving SARS-CoV-2 vaccines. Understanding the magnitude of protectivity granted by ‘hybrid immunity’, the combined response of infection- and vaccine-induced immunity, may impact vaccination strategies.MethodsA total of 36 synchronously infected (‘prior infection’) and, 33 SARS-CoV-2 naïve (‘naïve’) individuals participated. Participants provided sera six months after completing a round of BNT162b2 vaccination, to be processed for anti-spike antibody measurements and neutralization assays. The relationships between antibody titer, groups and age were explored.ResultsAnti-spike antibody titers at 6 months post-vaccination were significantly higher, reaching 13- to 17-fold, in the ‘prior infection’ group. Linear regression models showed that the enhancement in antibody titer attributable to positive infection history increased from 8.9- to 9.4- fold at age 30 to 19- to 32-fold at age 60. Sera from the ‘prior infection’ group showed higher neutralizing capacity against all six analyzed strains, including the Omicron variant.ConclusionsPrior COVID-19 led to establishing enhanced humoral immunity at 6 months after vaccination. Antibody fold-difference attributed to positive COVID-19 history increased with age, possibly because older individuals are prone to symptomatic infection accompanied by potentiated immune responses. Durable protection of hybrid immunity deserves reflection in vaccination campaigns.