Design of a pan-betacoronavirus vaccine candidate through a phylogenetically informed approach

Author:

Lewitus Eric12ORCID,Bai Hongjun12ORCID,Rolland Morgane12ORCID

Affiliation:

1. U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

2. Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.

Abstract

Coronaviruses are a diverse family of viruses that crossed over into humans at least seven times, precipitating mild to catastrophic outcomes. The severe acute respiratory syndrome coronavirus 2 pandemic renewed efforts to identify strains with zoonotic potential and to develop pan-coronavirus vaccines. The analysis of 2181 coronavirus genomes (from 102 host species) confirmed the limited sequence conservation across genera (alpha-, beta-, delta-, and gammacoronavirus) and proteins. A phylogenetically informed pan-coronavirus vaccine was not feasible because of high genetic heterogeneity across genera. We focused on betacoronaviruses and identified nonhuman-infecting receptor binding domain (RBD) sequences that were more genetically similar to human coronaviruses than expected given their phylogenetic divergence. These human-like RBDs defined three phylogenetic clusters. A vaccine candidate based on a representative sequence for each cluster covers the diversity estimated to protect against existing and future human-infecting betacoronaviruses. Our findings emphasize the potential value of conceptualizing prophylaxis against zoonoses in terms of genetic, rather than species, diversity.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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