npj Vaccines (Jul 2022)

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,
  • Hanne Andersen,
  • Christopher C. Stobart,
  • Melissa H. Bloodworth,
  • R. Stokes Peebles,
  • Yang Liu,
  • Xuping Xie,
  • Pei-Yong Shi,
  • Martin L. Moore,
  • Roderick S. Tang

DOI
https://doi.org/10.1038/s41541-022-00509-6
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 13

Abstract

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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.