Durable protection against the SARS-CoV-2 Omicron variant is induced by an adjuvanted subunit vaccine
Prabhu S. Arunachalam, Yupeng Feng, Usama Ashraf, Mengyun Hu, Alexandra C. Walls, Venkata Viswanadh Edara, Veronika I. Zarnitsyna, Pyone P. Aye, Nadia Golden, Marcos C. Miranda, Kristyn Moore Green, Breanna Threeton, Nicholas J. Maness, Brandon J. Beddingfield, Rudolf P. Bohm, Sarah E. Scheuermann, Kelly Goff, Jason Dufour, Kasi Russell‐Lodrigue, Elizabeth Kepl, Brooke Fiala, Samuel Wrenn, Rashmi Ravichandran, Daniel Ellis, Lauren Carter, Kenneth A. Rogers, Lisa Shirreff, Douglas E. Ferrell, Nihar R. Deb Adhikary, Jane Fontenot, Holly Hammond, Matthew B. Frieman, Alba Grifoni, Alessandro Sette, Derek T. O’Hagan, Robbert van der Most, Rino Rappuoli, François Villinger, Harry Kleanthous, Jay Rappaport, Mehul S. Suthar, David Veesler, Taia T. Wang, Neil P. King, Bali Pulendran
Abstract
Despite the remarkable efficacy of COVID-19 vaccines, waning immunity and the emergence of SARS-CoV-2 variants such as Omicron represents a global health challenge. Here, we present data from a study in nonhuman primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine comprising the receptor binding domain of the ancestral strain (RBD-Wu) on the I53-50 nanoparticle adjuvanted with AS03, which was recently authorized for use in individuals 18 years or older. Vaccination induced neutralizing antibody (nAb) titers that were maintained at high concentrations for at least 1 year after two doses, with a pseudovirus nAb geometric mean titer (GMT) of 1978 and a live virus nAb GMT of 1331 against the ancestral strain but not against the Omicron BA.1 variant. However, a booster dose at 6 to 12 months with RBD-Wu or RBD-β (RBD from the Beta variant) displayed on I53-50 elicited high neutralizing titers against the ancestral and Omicron variants. In addition, we observed persistent neutralization titers against a panel of sarbecoviruses, including SARS-CoV. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Vaccination resulted in protection against Omicron infection in the lung and suppression of viral burden in the nares at 6 weeks after the final booster immunization. Even at 6 months after vaccination, we observed protection in the lung and rapid control of virus in the nares. These results highlight the durable and cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine.