Humoral immune response to omicron infection in long-term Wuhan-Hu-1-imprinted population

Abstract

Recent WHO vaccination guidance no longer recommends COVID-19 vaccination beyond the first booster in low risk population, citing high population-level hybrid immunity due to widespread omicron infections.1 Although SARS-CoV-2 infection confers durable protection against reinfection,2-4 it may also produce immune imprinting, which skews subsequent immune response to variant antigens toward the first-exposed antigen based on the antigenic distance.5,6 China has the earliest and exclusively Wuhan-Hu-1(WH1)-imprinted population before the 2022 nation-wide omicron outbreak,7 which offers a unique opportunity to study long-term immune imprinting between most antigenically distant strains. Here, we assessed pseudovirus neutralization activity and anti-WH1 receptor binding domain (RBD) antibodies in 4 Chinese cohorts with hybrid or vaccine-only imprinting, or naïve to SARS-CoV-2 prior to omicron BF.7 infection. Both hybrid and vaccine-only imprinting augmented post-infection serum neutralization of WH1 and omicron sub-variants BF.7/BQ.1.1/XBB.1.5 comparing to naïve background. Feedback from pre-existing high-affinity antibodies limited the magnitude of humoral immune response to omicron infection without compromising protection, while antigenic seniority of pre-existing cross-reactive B cells only slightly reduces forward neutralization breadth in hybrid- and RBD vaccine-imprinted participants. Our results support the effectiveness of hybrid immunity against omicron reinfection in long-term imprinted population and provide immunological basis for similar epidemiological findings.8-10

Antibody responses in blood and saliva post COVID-19 bivalent booster do not reveal an Omicron BA.4/BA.5- specific response

“…A recent publication also indicated that the incorporation of the mRNA encoding the wildtype spike protein in this bivalent boost results in a deep immunological imprinting and the authors recommend its removal from future vaccinations (26). Our study cannot prove this theory, but it does support other studies that describe imprinting in the SARS-CoV-2 response (20)(21)(22)(23)(24)(25)(26). Additionally, a definitive analysis is difficult given that individuals greatly vary in infection and/or vaccination history, which can affect their immune responses to different SARS-CoV-2 variants in the future (28).…”