A Single Vaccination of Nonhuman Primates with Highly Attenuated Smallpox Vaccine, LC16m8, Provides Long-term Protection against Monkeypox

Abstract

Monkeypox virus (MPXV) causes human monkeypox (human MPX), which is a similar disease with smallpox in humans. A previous study showed that a single vaccination of monkeys with LC16m8, a highly attenuated smallpox vaccine, protected them from MPX at 4–5 weeks after vaccination. In the present study, we evaluated the long-term efficacy of a single vaccination with LC16m8 in a nonhuman primate model of MPXV infection. The monkeys were inoculated with LC16m8, Lister (parental strain of LC16m8), or mock and then challenged with MPXV via the subcutaneous route at 6 and 12 months after vaccination, which we compared with either Lister or mock vaccination. The LC16m8-monkeys exhibited almost no MPX-associated symptoms, whereas most of the naïve monkeys died. LC16m8 generated the protective memory immune response against MPXV, suggested from the immediate viremia reduction and the response of IgG antibody. The results demonstrate that the vaccination of monkeys with a single dose of LC16m8 provided durable protection against MPXV for longer than 1 year after immunization. Our results suggest that the vaccination of humans with LC16m8 could induce long-term protection against MPXV infection.