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

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.

Unravelling Antigenic Cross-Reactions toward the World of Coronaviruses: Extent of the Stability of Shared Epitopes and SARS-CoV-2 Anti-Spike Cross-Neutralizing Antibodies

“…However, there are still several possible biases in this hypothesis, since the bat Sarbecovirus remains to be discovered, the cross-reactive immunity reported has not been tested so far for neutralization of SARS-CoV-2, and there is a huge difference between in vitro neutralization of a virus and in vivo protection of humans against this virus. There are still teams that seek to identify a variant-proof strategy for the development of a pan-betacoronaviruses vaccine formulation [ 38 , 171 , 172 , 173 ]. Additional hypotheses refer to as cross-reaction between dengue virus (DENV) antibodies and the SARS-CoV-2 S1 RBD [ 174 ].…”

“…Immunological memory after infection with HCoV may potentially contribute to short lasting cross-protection against SARS-CoV-2. A recent comparison of the seven coronaviruses infecting human (the four HCoVs, as well as MERS-CoV and the two SARS-CoVs) indicated that overall amino acid sequence identity (pairwise gaps excluded) was low across these viruses, with 23.9% for the envelope (E), 36.2% for the membrane (M), 36.3% for nucleocapsid (N), and 29.5% for the spike (S), while it was 93% for E and 78% for S between the two SARS-CoVs [ 38 ]. This had already been reported decades ago, when research teams were searching for shared epitopes between HCoV and SARS-CoV-1.…”

The role of vaccines in the COVID-19 pandemic: what have we learned?

“…So far, several promising candidates have been developed. They include three classes: vaccines that contain a variety of RBD or spike proteins from different strains and isolates [ 115 , 116 ], vaccines based on the S2 of the spike protein [ 117 , 118 ], and consensus sequence approaches [ 119 ]. These approaches are similar to approaches taken for broadly protective or universal influenza virus vaccines and for HIV-1 vaccines [ 120 , 121 ].…”

SARS-CoV-2 outbreak: role of viral proteins and genomic diversity in virus infection and COVID-19 progression

“…It has been reported that all CoVs genera can infect animals [ 5 ]. Generally, Alphacoronavirus and Betacoronavirus infect mammals while Gammacoronavirus , and Deltacoronavirus infect both birds and mammals [ 6 ]. Interestingly, CoVs infection in human is only associated with Alphacoronaviruses and Betacoronaviruses genera [ 7 ].…”