A Penta-Component Mpox mRNA Vaccine Induced Protective Immunity in Naive and Simian Immunodeficiency Virus Infected Nonhuman Primates

Abstract

The recent worldwide outbreaks of mpox (monkeypox) prioritize the development of a safe and effective mRNA vaccine. The contemporary mpox virus (MPXV) showed changing virological and epidemiological features, notably affecting populations already vulnerable to human immunodeficiency virus (HIV). Herein, we profiled the immunogenicity and protection of AR-MPXV5, a novel penta-component mRNA vaccine targeting five specific proteins (M1R, E8L, A29L, A35R, and B6R) from the representative contemporary MPXV clade II strain, in both naive and simian immunodeficiency virus (SIV)-infected nonhuman primates. Immunization with two doses of AR-MPXV5 to cynomolgus macaques resulted in robust antibody responses and cellular responses. Importantly, based on the challenge model with a contemporary MPXV clade II strain, AR-MPXV5 provided excellent protection in preventing skin lesions, eliminating viremia and reducing viral loads in multiple tissues including testis after challenge, thereby obviating the possibility of secondary sexual transmission. More importantly, AR-MPXV5 was well-tolerated in stable chronic SIV-infected rhesus monkeys, and comparable MPXV-specific humoral and cellular responses were elicited in both naive and SIV-infected monkeys. Together, these results support further clinical development of the AR-MPXV5 vaccine.