The current worldwide monkepox outbreak has reaffirmed the continued threat monkeypox virus (MPXV) poses to public health.
JYNNEOS, a Modified
Vaccinia Ankara (MVA)-based live, non-replicating
vaccine, was recently approved for
monkeypox prevention for adults at high risk of MPXV
infection in the United States. Although the safety and immunogenicity of
JYNNEOS have been examined previously, the clinical cohorts studied largely derive from regions where MPXV does not typically circulate. In this study, we assess the quality and longevity of serological responses to two doses of
JYNNEOS vaccine in a large cohort of healthcare workers from the Democratic Republic of Congo (DRC). We show that
JYNNEOS elicits a strong orthopoxvirus (OPXV)-specific antibody response in participants that peaks around day 42, or 2 weeks after the second
vaccine dose. Participants with no prior history of
smallpox vaccination or exposure have lower baseline antibody levels, but experience a similar fold-rise in antibody titers by day 42 as those with a prior history of vaccination. Both previously naïve and vaccinated participants generate vaccinia virus and MPXV-
neutralizing antibody in response to
JYNNEOS vaccination. Finally, even though total OPXV-specific
IgG titers and
neutralizing antibody titers declined from their peak and returned close to baseline levels by the 2-year mark, most participants remain
IgG seropositive at the 2-year timepoint. Taken together, our data demonstrates that
JYNNEOS vaccination triggers potent OPXV
neutralizing antibody responses in a cohort of healthcare workers in DRC, a
monkeypox-endemic region. MPXV vaccination with
JYNNEOS may help ameliorate the disease and economic burden associated with
monkeypox and combat potential outbreaks in areas with active virus circulation.