Synthetic modified vaccinia Ankara vaccines confer potent monkeypox immunity in non-human primates and healthy adults

Abstract

The recent outbreak of monkeypox outside its endemic boundaries has attracted global attention and prompted world leaders to reserve thousands of doses of the only approved third-generation smallpox/monkeypox vaccine Jynneos, which is based on the highly attenuated modified vaccinia Ankara (MVA) vector. Given the potential urgency to vaccinate individuals at risk in both endemic and non-endemic countries to curtail further spread of the outbreak, there is a legitimate need for substantial doses of smallpox/monkeypox vaccines. We previously developed COH04S1, a multiantigen SARS-CoV-2 vaccine candidate built on a synthetic MVA platform. COH04S1 was found to be safe and to induce SARS-CoV-2-specific immune responses in healthy adults participating in a phase 1, blinded, randomized, placebo-controlled clinical trial. Here we perform a retrospective analysis of vaccine-induced orthopoxvirus immunity in a subgroup of volunteers enrolled in the phase 1 clinical trial that were vaccinated with COH04S1 at different doses. At all dose levels, vaccination with COH04S1 resulted in robust MVA-specific binding and neutralizing antibody responses, which were sustained over six months post-vaccination. Similarly, both CD8+ and CD4+ T cells specific for MVA were induced by COH04S1 vaccination and remained durable for at least six months. Given that both arms of the immune response are thought to be involved in protection against orthopoxvirus infections, our results indicate that COH04S1 or other sMVA-based vaccines may represent valuable candidates for smallpox/monkeypox vaccination.

Update on monkeypox virus infection: Focusing current treatment and prevention approaches

“…Individuals suffering from severe Mpox infection or susceptible people with T-cell immunodeficiency, for whom smallpox immunization is not recommended, may get relief from intravenous vaccinia immune globulin as prophylactic. However, the extent of recovery from antiviral therapy or VIGIV is not yet known [27,61].…”