Mucosal administration of a live attenuated recombinant COVID-19 vaccine protects nonhuman primates from SARS-CoV-2
Mariana F. Tioni, Robert Jordan, Angie Silva Pena, Aditya Garg, Danlu Wu, Shannon I. Phan, Christopher M. Weiss, Xing Cheng, Jack Greenhouse, Tatyana Orekov, Daniel Valentin, Swagata Kar, Laurent Pessaint, Hanné Andersen, Christopher C. Stobart, Melissa H. Bloodworth, R. Stokes Peebles, Yang Liu, Xuping Xie, Pei‐Yong Shi, Martin L. Moore, Roderick S. Tang
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 is an enveloped RNA virus that relies on its trimeric surface glycoprotein spike for entry into host cells. Here we describe the COVID-19 vaccine candidate MV-014-212, a live, attenuated, recombinant human respiratory syncytial virus expressing a chimeric SARS-CoV-2 spike as the only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration of MV-014-212 in AGMs protected against SARS-CoV-2 challenge, reducing by more than 200-fold the peak shedding of SARS-CoV-2 in the nose. MV-014-212 elicited mucosal immunoglobulin A in the nose and neutralizing antibodies in serum that exhibited cross-neutralization against virus variants of concern Alpha, Beta, and Delta. Intranasally delivered, live attenuated vaccines such as MV-014-212 entail low-cost manufacturing suitable for global deployment. MV-014-212 is currently in Phase 1 clinical trials as an intranasal COVID-19 vaccine.