Serological responses to the MVA-based JYNNEOS monkeypox vaccine in a cohort of participants from the Democratic Republic of Congo

Abstract

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.

Keywords: Antibody; Immunogenicity; JYNNEOS; MVA; Monkeypox; Orthopoxvirus; Serology.

Fig. 1

Detection of IgM and IgG antibody after JYNNEOS vaccination. Serum specimens from participants were tested at a single dilution by ELISA to check for the presence of VACV-specific IgM and IgG at different time points after vaccination. IgM (A) and IgG (B) OD-COV values shown for Naïve (left column) and Prior Vaccination (right column) groups. OD-COV values plotted in box-and-whiskers format, wherein the horizontal band shows the median, boxes and whiskers represent 25–75 percentile and 2.5–97.5 percentile, respectively. (C) Magnitude and kinetic trends of VACV-specific IgM and IgG in Naïve vs Prior Vaccination groups. Median IgM (blue) and IgG (red) OD-COV values from (A) and (B) shown with respect to days post primary vaccination. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Robust IgG production after JYNNEOS vaccination. D0, D42 and D730 serum specimens from participants were serially diluted and tested by ELISA to determine VACV-specific IgG endpoint titers (EPTs). IgG EPTs shown for Naïve (A) and Prior Vaccination (B) groups. Statistical significance determined using one-way ANOVA with post-hoc Tukey’s multiple comparisons test. P-values represented as asterisks. *p < 0.05, **p < 0.01 and ****p < 0.0001, ns: not significant. C) Fold change in VACV-specific IgG EPTs between D0 and D42 (left) and D0 and D730 (right) for Naïve and Prior Vaccination groups. Graphs show individual data points and mean values +/- SEM. Median values tabulated below respective graphs.

Fig. 3

VACV and MPXV neutralizing antibodies generated post JYNNEOS vaccination. D0, D42 and D730 serum specimens were serially diluted and tested by PRNT to determine serum neutralization capacity. PRNT50 values against VACV (A) and MPXV (B) shown for Naïve (left column) and Prior Vaccination (right column) participants. Dotted lines signify the highest serum dilution tested (1:7.5). Graphs show individual data points and mean values +/- SEM. Samples with PRNT50 values below the limit of detection were assigned a value of y = 4 so they could be presented graphically. (C) Linear regression plots of log₁₀ transformed PRNT50 vs IgG OD-COV values (left) and log₁₀ transformed PRNT50 vs log₁₀ transformed IgG EPT (right). The dotted lines mark the 95 % prediction band of the best-fit line (bold).