Single Dose of Mpox Vaccine Series Appears to Give Partial Protection

One dose of the modified vaccinia Ankara-Bavarian Nordic (MVA-BN; Jynneos) mpox vaccine was moderately effective in preventing mpox infections, according to a Canadian observational, emulated target trial.

Among 3,204 men who received a first dose of the MVA-BN vaccine, 21 were diagnosed with laboratory-confirmed mpox versus 50 out of 3,204 who were unvaccinated (HR 0.42, 95% CI 0.25-0.69) over the study period of 153 days, for an estimated one-dose vaccine effectiveness of 58%, reported Sharmistha Mishra, MD, PhD, MSc, of the University of Toronto, and colleagues in BMJ.

This translated into 0.09 infections per 1,000 person-days (95% CI 0.05-0.13) in the vaccinated group and 0.2 infections per 1,000 person-days (95% CI 0.15-0.27) in the unvaccinated group over the course of the study.

“We were not surprised by our findings, because previous observational studies reported one-dose effectiveness of MVA-BN against mpox infection to be 36% to 86%,” study co-author Jeff Kwong, MD, MSC, also of the University of Toronto, told MedPage Today.

“This study reinforces the benefit in vaccinating against mpox with MVA-BN and reaffirms that a single dose provides at least moderate protection for communities vulnerable to mpox,” Aniruddha Hazra, MD, an infectious disease expert at Howard Brown Health in Chicago, told MedPage Today.

The study also aimed to reduce biases and confounding variables seen in previous observational studies, Hazra noted. However, “their final results are not very surprising,” he said. “Their calculated vaccine effectiveness mostly aligns with what we currently expect to see with a single dose of MVA-BN.”

In Canada and the U.S., the MVA-BN vaccine is recommended as a two-dose vaccine given 28 days apart. However, during the first mpox outbreak in 2022, the vaccine was given as a single dose or using a reduced amount of vaccine due to concerns about limited vaccine supply.

In August, the World Health Organization declared its second global mpox emergency in response to rapid surge of the mpox clade I variant in Africa and a rising number of cases in children.

Mpox infections in Canada and across the globe are rising again in 2024, Mishra and colleagues wrote, with most diagnoses among individuals who have not yet been vaccinated or have received only a single dose of vaccine.

“Given the moderate effectiveness of a single dose, achieving high coverage with a full course could be important to prevent and manage ongoing transmission globally and prevent a large resurgence,” they commented

“It’s important to advise those who are at risk of mpox infection — which at the moment includes gay/bisexual/other men who have sex with men and sex workers — to receive MVA-BN as soon as possible so that they have some protection against mpox infection,” Kwong added, especially in the current setting of the global public health emergency.

In the U.S., another mpox vaccine, ACAM2000, was recently approved; it is a single-dose vaccine.

Study authors pointed out that randomized clinical trials of vaccination against mpox have yet to be conducted.

Mishra and two colleagues explained in an accompanying article that because clinical trials were infeasible — and sometimes unethical — in the face of a global health emergency, researchers have relied on observational studies to estimate how well the mpox vaccine worked.

Although this was also an observational study, researchers used a target trial emulation design, meaning it incorporated features of randomized trials. They also performed sensitivity analyses to determine residual confounding.

The ability of a vaccine to prevent laboratory confirmed infection is only one parameter of vaccine effectiveness, they pointed out. For example, this study did not assess how well the MVA-BN vaccine reduced symptomatic infection or infection severity, or if it induced herd immunity.

Even so, “our finding suggests that the regional MVA-BN vaccination program may have been a contributing factor in slowing mpox transmission in the region in 2022,” they said.

The study, conducted during the first mpox surge in Canada from May 2022 through October 2022, matched data from men who received the vaccine with unvaccinated controls by age, geographical region, past HIV diagnosis, bacterial sexually transmitted infection (STI) diagnoses in the past 3 years, and receipt of non-MVA-BN vaccines in the previous year. The median age of matched participants was 35, 66% were residents of Toronto, and about 22% had been previously diagnosed with HIV.

To confirm specificity of the association of vaccination with reduced infection rates, researchers performed sensitivity analyses and found that vaccination was not associated with a reduced rate of mpox infection during the first 14 days post-vaccination (prior to expected antibody response) nor with bacterial STI diagnoses, which would not be affected by the vaccine.

Only a few study participants had received a second dose (13.7%) by the end of the study period, so researchers were unable to evaluate the effectiveness of the two-dose series.

The authors acknowledged several limitations of their study. The final cohort comprised 10% or less of first-dose MVA-BN vaccinations and mpox diagnoses in Ontario during the study period, resulting in decreased sample sizes. Some patient information, such as previous smallpox vaccination or sexual exposures, was not available. Also, the study population may have missed at-risk men with poor access to healthcare, resulting in selection bias. Finally, the study only included laboratory-confirmed infection which may have missed additional cases, leading to an overestimation of vaccine effectiveness.