Vaccine Effectiveness of Modified Vaccinia Ankara in Human Monkeypox

Abstract

BackgroundThe recent global outbreak of the human monkeypox virus (MPXV) was declared a public health emergency by the World Health Organization. Modified Vaccinia Ankara (MVA) is currently the only FDA-approved vaccine against MPXV that was approved for this indication based on a study in non-human primates. Since there is currently scarce evidence of the efficacy in humans, our objective was to evaluate real-life vaccine effectiveness (VE) after providing one vaccine dose to individuals at risk of MPVX infection.MethodsThe study cohort included all Clalit Health Services (CHS) members estimated to be at moderate to high risk for MPXV infection. The study commenced on July 31, 2022, when the MVA vaccination campaign was initiated in CHS, and participants were followed until August 10, 2022. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association between vaccination and MPXV infections with adjustment for sociodemographic and clinical risk factors.Results8,168 subjects met the study eligibility criteria (0.17% of CHS members). Of them, 626 (7.7%) were vaccinated with MVA and completed at least 7 days of follow-up. 14 infections were confirmed in CHS during the study period, all within the study cohort and all in unvaccinated participants. VE was estimated at 100% (95% CI: 100%-100%).ConclusionsThese short-term preliminary results suggest a very high VE of a single dose of MVA for MPVX infection in moderate to high-risk individuals. These findings suggest that urgent MVA vaccination of high-risk subjects may contribute to outbreak containment.

Monkeypox Virus Cross-Neutralizing Antibodies in Clinical Trial Participants Vaccinated With Modified Vaccinia Virus Ankara Encoding Middle East Respiratory Syndrome–Coronavirus Spike Protein

“…The formation of robust MPXV nAbs only after 3 doses of MVA-MERS-S raises the question whether high-risk individuals currently being vaccinated with MVA-BN would benefit from an additional booster. However, a preliminary analysis of an observational cohort study suggests high effectiveness against MPXV infection of even a single dose of MVA-BN in moderate- to high-risk individuals [ 15 ]. It is possible that the nAbs present at the time of virus exposure are not what protects the vaccinated individual.…”

Characterizing the acute antibody response of monkeypox and MVA‐BN vaccine following an Australian outbreak

“…The results from a bivalent MVA‐MERS CoV vaccine study examining serological responses to MERS CoV, MVA, and MPXV have demonstrated superior antibody profiles following three doses; with 100% of subjects with detectable MPXV neutralizing antibodies following the third dose, improving from 30% after two doses 40 ; a finding also echoed in another study 21 . Despite the low levels of antibodies following one dose of the MVA‐BN vaccine, cohort studies have shown an effectiveness of 78%–79% in preventing symptomatic mpox following just one dose of MVA‐BN 19,41 . However, recent cases of breakthrough infection despite two‐doses of MVA‐BN brings debate about the effectiveness of the two‐dose regime, and preliminary findings suggest that the durability of the antibody response and longitudinal protection afforded by the vaccine to be only modest 32,42,43 .…”

“…21 Despite the low levels of antibodies following one dose of the MVA-BN vaccine, cohort studies have shown an effectiveness of 78%-79% in preventing symptomatic mpox following just one dose of MVA-BN. 19,41 However, recent cases of breakthrough infection despite two-doses of MVA-BN brings debate about the effectiveness of the two-dose regime, and preliminary findings suggest that the durability of the antibody response and longitudinal protection afforded by the vaccine to be only modest. 32,42,43 While no serologic correlate of protection has been defined for monkeypox, studies have suggested a neutralizing antibody titer of >1:20 or >1:32 for protection against smallpox.…”

“…Although a diverse landscape of cellular immunity has been shown to be influential in the protection against Poxviruses, the unique role of antibodies has been highlighted through OPV challenge studies of Macaques; in which B‐Cell depleted subjects experienced increased disease manifestation and death, conversely, T‐Cell depleted subjects were found to have good clinical outcomes 16–18 . The MVA‐BN vaccine has been reported to be protective against MPXV infection and to induce complete seroconversion after two doses 19–21 . Stable antibody levels have been reported in the decades following the first‐generation Smallpox vaccine (Dryvax); with detectable cross‐neutralizing responses against MPXV at greater than 40 years postimmunisation 21,22 …”

“…[16][17][18] The MVA-BN vaccine has been reported to be protective against MPXV infection and to induce complete seroconversion after two doses. [19][20][21] Stable antibody levels have been reported in the decades following the first-generation Smallpox vaccine (Dryvax); with detectable cross-neutralizing responses against MPXV at greater than 40 years postimmunisation. 21,22 The acute humoral response following mpox infection and vaccination with MVA-BN has been recently described, 23,24 and further characterization of the antibody response to infection and vaccination is of considerable interest following the unprecedented dissemination of MPXV in 2022.…”