TY - JOUR T1 - Durable protection against SARS-CoV-2 Omicron induced by an adjuvanted subunit vaccine JF - bioRxiv DO - 10.1101/2022.03.18.484950 SP - 2022.03.18.484950 AU - Prabhu S. Arunachalam AU - Yupeng Feng AU - Usama Ashraf AU - Mengyun Hu AU - Venkata Viswanadh Edara AU - Veronika I. Zarnitsyna AU - Pyone Pyone Aye AU - Nadia Golden AU - Kristyn W. M. Green AU - Breanna M. Threeton AU - Nicholas J. Maness AU - Brandon J. Beddingfield AU - Rudolf P. Bohm AU - Jason Dufour AU - Kasi Russell-Lodrigue AU - Marcos C. Miranda AU - Alexandra C. Walls AU - Kenneth Rogers AU - Lisa Shirreff AU - Douglas E Ferrell AU - Nihar R. Deb Adhikary AU - Jane Fontenot AU - Alba Grifoni AU - Alessandro Sette AU - Derek T. O’Hagan AU - Robbert Van Der Most AU - Rino Rappuoli AU - Francois Villinger AU - Harry Kleanthous AU - Jay Rappaport AU - Mehul S. Suthar AU - David Veesler AU - Taia T. Wang AU - Neil P. King AU - Bali Pulendran Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/03/20/2022.03.18.484950.abstract N2 - 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. ER -