BA.1 breakthrough infection elicits distinct antibody and memory B cell responses in vaccinated-only versus hybrid immunity individuals

• DOI: 10.1016/j.isci.2025.111962
• Publication Date: 2025-02-06T00:19:24Z
• Authors: Carla Saade; Timothée Bruel; Lou-Léna Vrignaud; Martin Killian; Annabelle Drouillard; Véronique Barateau; Maxime Espi; Natacha Mariano; Charlotte Mignon; Lily Bruyère; Liliane Khoryati; William Henry Bol...; Olivier Schwartz; Bruno Lina; Martine Valette; Olivier Thaunat; Jean-Baptiste Fas...; Nicolas Guibert; Gregory Destras; Dulce Alfaiate; Amélie Massardier...; Antonin Bal; Hélène Lozano; Bouchra Mokdad; Kahina Saker; Cécile Barnel; Caroline Dupré; Fanny Joubert; Camille Mena; Virginie Pitiot; Vanessa Escuret; Florence Morfin; Mary-Anne Trabaud; Laurence Josset; Antonin Bal; Bruno Pozzetto; Stéphane Paul; Thierry Walzer; Sophie Trouillet-...
• Keywords: 570; SARS-CoV-2; [SDV]Life Sciences [q-bio]; Science; breakthrough infection; Immunology; Q; Health sciences; immune response; ADCC function; [SDV] Life Sciences [q-bio]; Virology; 616; hybrid immunity; IgG4 class-switching

Summary: Immune memory is influenced by the frequency and type of antigenic challenges. Here, we performed a cross-sectional comparison of immune parameters following a BA.1 breakthrough infection in individuals with prior hybrid immunity (conferred by infection and vaccination) versus those solely vaccinated in a cohort of health care workers in Lyon, France. The results showed higher levels of serum anti-receptor binding domain (RBD) antibodies and neutralizing antibodies against BA.1 post-infection in the vaccine-only group. Individuals in this group also showed a decrease in memory B cells against the ancestral strain but an increase in those specific and cross-reactive to BA.1, suggesting a more limited immune imprinting. Conversely, hybrid immunity prevents the decrease in antibody dependent cellular cytotoxicity (ADCC) response, possibly by limiting IgG4 class-switching and enhanced anti-N responses post-infection. This highlights that BA.1 breakthrough infection induces different immune responses depending on prior history of vaccination and infection, which should be considered for further vaccination guidelines.