SARS-CoV-2 binding and neutralizing antibody levels after vaccination with Ad26.COV2.S predict durable protection in rhesus macaques

Roozendaal, Ramon; Solforosi, Laura; Stieh, Daniel; Serroyen, Jan; Straetemans, Roel; Wegmann, Frank; Rosendahl Huber, Sietske K.; van der Lubbe, Joan E. M.; Hendriks, Jenny; le Gars, Mathieu; Dekking, Liesbeth; Czapska-Casey, Dominika N.; Guimera, Nuria; Janssen, Sarah; Tete, Sarah; Chandrashekar, Abishek; Mercado, Noe; Yu, Jingyou; Koudstaal, Wouter; Sadoff, Jerry; Barouch, Dan H.; Schuitemaker, Hanneke; Zahn, Roland

The first COVID-19 vaccines have recently gained authorization for emergency use.1,2 At this moment, limited knowledge on duration of immunity and efficacy of these vaccines is available. Data on other coronaviruses after natural infection suggest that immunity to SARS-CoV-2 might be short lived,3,4 and preliminary evidence indicates waning antibody titers following SARS-CoV-2 infection.5 Here we model the relationship between immunogenicity and protective efficacy of a series of Ad26 vectors encoding stabilized variants of the SARS-CoV-2 Spike (S) protein in rhesus macaques6,7,8 and validate the analyses by challenging macaques 6 months after immunization with the Ad26.COV2.S vaccine candidate that has been selected for clinical development. We find that Ad26.COV2.S confers durable protection against replication of SARS-CoV-2 in the lungs that is predicted by the levels of S-binding and neutralizing antibodies. These results suggest that Ad26.COV2.S could confer durable protection in humans and that immunological correlates of protection may enable the prediction of durability of protection.