%0 Journal Article %A Zijun Wang %A Frauke Muecksch %A Friederike Muenn %A Alice Cho %A Shuai Zong %A Raphael Raspe %A Victor Ramos %A Brianna Johnson %A Tarek Ben Tanfous %A Justin DaSilva %A Eva Bednarski %A Camila Guzman-Cardozo %A Martina Turroja %A Katrina G. Millard %A Pinkus Tober-Lau %A David Hillus %A Kai-Hui Yao %A Irina Shimeliovich %A Juan Dizon %A Anna Kaczynska %A Mila Jankovic %A Anna Gazumyan %A Thiago Y. Oliveira %A Marina Caskey %A Paul D. Bieniasz %A Theodora Hatziioannou %A Florian Kurth %A Leif Erik Sander %A Michel C. Nussenzweig %A Christian Gaebler %T Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens %D 2022 %R 10.1101/2022.05.13.491823 %J bioRxiv %P 2022.05.13.491823 %X The SARS-CoV-2 pandemic prompted a global vaccination effort and the development of numerous COVID-19 vaccines at an unprecedented scale and pace. As a result, current COVID- 19 vaccination regimens comprise diverse vaccine modalities, immunogen combinations and dosing intervals. Here, we compare vaccine-specific antibody and memory B cell responses following two-dose mRNA, single-dose Ad26.COV2.S and two-dose ChAdOx1 or combination ChAdOx1/mRNA vaccination. Plasma neutralizing activity as well as the magnitude, clonal composition and antibody maturation of the RBD-specific memory B cell compartment showed substantial differences between the vaccination regimens. While individual monoclonal antibodies derived from memory B cells exhibited similar binding affinities and neutralizing potency against Wuhan-Hu-1 SARS-CoV-2, there were significant differences in epitope specificity and neutralizing breadth against viral variants of concern. Although the ChAdOx1 vaccine was inferior to mRNA and Ad26.COV2.S in several respects, biochemical and structural analyses revealed enrichment in a subgroup of memory B cell neutralizing antibodies with distinct RBD-binding properties resulting in remarkable potency and breadth.Competing Interest StatementThe Rockefeller University has filed a provisional patent application in connection with this work on which M.C.N. is an inventor (US patent 63/021,387). P.D.B. has received remuneration from Pfizer for consulting services relating to SARS-CoV-2 vaccines. %U https://www.biorxiv.org/content/biorxiv/early/2022/05/13/2022.05.13.491823.full.pdf