For rapidly mutating viruses such as influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immune memory recalled by antigenically drifted variants primarily comprises antibodies that cross-react to the priming strain rather than de novo elicited responses, a phenomenon termed original antigenic sin or immune imprinting. The composition and functionality of de novo responses elicited by variant exposures remain unclear. Here we isolated and characterized hundreds of recall and de novo neutralizing monoclonal antibodies after sequential exposures to SARS-CoV-2 variants in ancestral-imprinted humans. De novo variant type-specific antibodies used different V(D)J genes that were closer to germline sequence, potently neutralized future variants and targeted distinct receptor binding domain epitopes compared to ancestral cross-reactive (recall) antibodies. Nevertheless, neutralizing responses to the updated 2024–2025 booster were predominantly ancestral cross-reactive. These results reveal the distinct contributions of recall and de novo antibodies to a balanced immune response and underscore the benefit of updated booster vaccines, which augment both subsets. Updated SARS-CoV-2 boosters broaden humoral immunity by recalling cross-reactive antibodies and eliciting new less cross-reactive Omicron type-specific antibodies that target distinct RBD epitopes and more potently neutralize recent variants.
T. Johnston, S. Li, M. Painter et al.· Nature Immunology· 2 citations
Data on immune responses to COVID-19 vaccination in West and Central Africa remain limited, particularly across SARS-CoV-2 variants and vaccine platforms. Using the InVITE cohort in the Democratic Republic of Congo, Guinea, Liberia, and Mali, we evaluated anti-spike (anti-S) antibody binding to nine SARS-CoV-2 variants in 96 participants equally selected from pre-vaccination assay defined seropositive and seronegative groups. Participants received mRNA, adenovirus-vectored, or inactivated virus vaccines. Anti-S binding was measured before vaccination and two months after completion of the primary series using a Meso Scale Discovery 10-plex assay. Before vaccination, antibody binding was significantly higher against pre-Omicron variants (Ancestral, Alpha, Beta, and Delta) than Omicron variants in both seronegative (fold change [FC] 3.85, 99% CI 3.45–4.17) and seropositive (FC 3.57, 99% CI 3.33–3.84) participants. Seropositive individuals showed greater binding than seronegative individuals across all variants. Two months post-vaccination, mRNA vaccines elicited higher antibody binding than adenovirus-vectored or inactivated vaccines, whereas no significant differences were observed between adenovirus-vectored and inactivated vaccines. Antibody binding remained higher against pre-Omicron than Omicron variants across all vaccine platforms and serostatus groups. These findings provide rare data on variant-specific vaccine-elicited antibody binding responses in West and Central African populations with distinct demographic, epidemiologic, and immunologic background.
Trial registration: Registration ClinicalTrials.gov: NCT05096091, Registration date: 10-26-2021, Clinical trial registry:
https://clinicaltrials.gov/study/NCT05096091?term=NCT05096091rank=1#study-overview
.
E. Lusamaki, Ana M. Ortega-Villa, Daouda Camara et al.· Scientific Reports· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
