RT Journal Article SR Electronic T1 Durable protection against SARS-CoV-2 Omicron induced by an adjuvanted subunit vaccine JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.03.18.484950 DO 10.1101/2022.03.18.484950 A1 Prabhu S. Arunachalam A1 Yupeng Feng A1 Usama Ashraf A1 Mengyun Hu A1 Venkata Viswanadh Edara A1 Veronika I. Zarnitsyna A1 Pyone Pyone Aye A1 Nadia Golden A1 Kristyn W. M. Green A1 Breanna M. Threeton A1 Nicholas J. Maness A1 Brandon J. Beddingfield A1 Rudolf P. Bohm A1 Jason Dufour A1 Kasi Russell-Lodrigue A1 Marcos C. Miranda A1 Alexandra C. Walls A1 Kenneth Rogers A1 Lisa Shirreff A1 Douglas E Ferrell A1 Nihar R. Deb Adhikary A1 Jane Fontenot A1 Alba Grifoni A1 Alessandro Sette A1 Derek T. O’Hagan A1 Robbert Van Der Most A1 Rino Rappuoli A1 Francois Villinger A1 Harry Kleanthous A1 Jay Rappaport A1 Mehul S. Suthar A1 David Veesler A1 Taia T. Wang A1 Neil P. King A1 Bali Pulendran YR 2022 UL http://biorxiv.org/content/early/2022/03/20/2022.03.18.484950.abstract AB Despite the remarkable efficacy of COVID-19 vaccines, waning immunity, and the emergence of SARS-CoV-2 variants such as Omicron represents a major global health challenge. Here we present data from a study in non-human primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine, consisting of RBD (receptor binding domain) on the I53-50 nanoparticle, adjuvanted with AS03, currently in Phase 3 clinical trial (NCT05007951). Vaccination induced robust neutralizing antibody (nAb) titers that were maintained at high levels for at least one year after two doses (Pseudovirus nAb GMT: 2207, Live-virus nAb GMT: 1964) against the ancestral strain, but not against Omicron. However, a booster dose at 6-12 months with RBD-Wu or RBD-β (RBD from the Beta variant) displayed on I53-50 elicited equivalent and remarkably high neutralizing titers against the ancestral as well as the Omicron variant. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Importantly, vaccination resulted in protection against Omicron infection in the lung (no detectable virus in any animal) and profound suppression of viral burden in the nares (median peak viral load of 7567 as opposed to 1.3×107 copies in unvaccinated animals) at 6 weeks post final booster. Even at 6 months post vaccination, there was significant protection in the lung (with 7 out of 11 animals showing no viral load, 3 out of 11 animals showing ~20-fold lower viral load than unvaccinated controls) and rapid control of virus in the nares. These results highlight the durable cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine platform.Competing Interest StatementB.P. serves on the External Immunology Board of GlaxoSmithKline, and on the Scientific Advisory Board of Sanofi, Medicago, CircBio and Boehringer-Ingelheim. D.T.O., R.V.D.M., and R.R. are employees of GSK group of companies. H.K. is an employee of Bill and Melinda Gates Foundation. C.- A.S. is a consultant for Gritstone Bio, Flow Pharma, Arcturus Therapeutics, ImmunoScape, CellCarta, Avalia, Moderna, Fortress and Repertoire. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work.