Monkeypox virus quadrivalent mRNA vaccine induces antibody responses and cellular immunity and protects mice against Vaccinia virus (preprint)

There is an urgent need for efficient and safe vaccines against the monkeypox virus (MPXV) in response to the rapidly spreading monkeypox epidemic. In the age of COVID-19, mRNA vaccines have been highly successful and emerged as platforms enabling rapid development and large-scale preparation. Here, we have developed two MPXV quadrivalent mRNA vaccines, named mRNA-A-LNP and mRNA-B-LNP, based on two IMVs (A29L and M1R) and two EEVs (A35R and B6R). By administering mRNA-A-LNP and mRNA-B-LNP intramuscularly twice, mice have induced MPXV-specific IgG antibodies and potent Vaccinia virus (VACV)-specific neutralizing antibodies. Additionally, it elicited durable MPXV-specific killer memory T-cell immunity as well as memory B-cell immunity in mice. Furthermore, the passive transfer of sera from mRNA-A-LNP and mRNA-B-LNP-immunized mice protected nude mice against the VACV challenge. In addition, two doses of mRNA-A-LNP and mRNA-B-LNP were also protective against the VACV challenge in mice. Overall, our results demonstrated that mRNA-A-LNP and mRNA-B-LNP appear to be safe and effective vaccine candidates against monkeypox epidemics, as well as against outbreaks caused by other orthopoxviruses, including the smallpox virus.

A framework for predicting potential host ranges of pathogenic viruses based on receptor ortholog analysis (preprint)

Viral zoonoses are a serious threat to public health and global security, as reflected by the current scenario of the growing number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. However, as pathogenic viruses are highly diverse, identification of their host ranges remains a major challenge. Here, we present a combined computational and experimental framework, called REceptor ortholog-based POtential virus hoST prediction (REPOST), for the prediction of potential virus hosts. REPOST first selects orthologs from a diverse species by identity and phylogenetic analyses. Secondly, these orthologs is classified preliminarily as permissive or non-permissive type by infection experiments. Then, key residues are identified by comparing permissive and non-permissive orthologs. Finally, potential virus hosts are predicted by a key residue-specific weighted module. We performed REPOST on SARS-CoV-2 by studying angiotensin-converting enzyme 2 orthologs from 287 vertebrate animals. REPOST efficiently narrowed the range of potential virus host species (with 95.74% accuracy).