Interim data from a phase II trial demonstrate the safety and tolerability of the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine in adolescents. MVA-BN is a live attenuated, non-replicating orthopoxvirus vaccine licensed in the US for smallpox and mpox prevention.

“Mpox is a re-emerging disease [and a global public health threat] … Vaccination is a mitigation strategy in current mpox outbreaks for those exposed and those at higher risk of exposure to mpox,” said Dr C Mary Healy from the Baylor College of Medicine, Houston, Texas, US, at IDWeek 2024.

There are two vaccines for both smallpox and mpox approved by the FDA for use in adults, but only one of these is available under Emergency Use Authorization for individuals aged <18 years that is recommended if the risk is high, she noted. “An FDA-approved mpox vaccine for adolescents is a public health need.”

The team conducted an open-label, non-placebo controlled trial evaluating a two-dose regimen of 1x10⁸ TCID₅₀ MVA-BN administered subcutaneously on days 1 and 29 in healthy, vaccinia-naive adolescents aged 12?17 years (n=315; mean age 14.4 years, 51 percent male) compared with adults aged 18?50 years (n=211; mean age 34.9 years, 45 percent male). Participants were followed for 13 months. [IDWeek 2024, abstract 579]

Participants should be willing to follow public health advice regarding mpox avoidance. Female participants must be amenable to using effective contraception for a month prior to enrolment up to day 57. Individuals with well-controlled HIV were allowed to participate. All participants received dose 1; >98 percent received dose 2. Over 97 percent completed the primary endpoint (day 43).

Solicited systemic reaction rates were similar between adolescents and adults after either dose (74 percent and 73 percent, respectively). The most common systemic reactions were fatigue (52 percent and 56 percent) and headache (50 percent and 49 percent).

A similar pattern was seen for solicited local reactions (88 percent and 91 percent for adolescents and adults, respectively). The most common local reactions were pain at injection site (74 percent and 81 percent) and erythema/redness (61 percent and 66 percent).

Vaccination-related dizziness was reported more frequently in adolescents than adults (9 vs 0 events). “No event resulted in syncope, medical attention, or product discontinuation. The rates were similar to those reported with other adolescent vaccines, ” noted Healy.

The most common unsolicited adverse event was injection site nodule. Product discontinuation rate was low at <1 percent in adolescents and 1 percent in adults. “Overall, MVA-BN was generally well tolerated in both groups,” said Healy.

Day-43 antibody response

Day-43 samples were obtained from 304 adolescents and 208 adults who met the criteria for the modified intention-to-treat analysis.

Day 1 geometric mean titres (GMTs) for adolescents and adults were 10 and 10.9, respectively (GMT ratio [GMTR], 0.92). By day 29 (post-first dose), the corresponding GMTs were 51.1 and 44.4 (GMTR, 1.15).

The peak antibody response in adolescents was noninferior to that observed in adults on any post-vax day (GMT, 450.6 vs 295; GMTR, 1.53; p<0.001). This effect was sustained after dose 2 (day 43; GMT, 470.3 vs 293.2; GMTR, 1.60; p<0.001). “The results in adolescents were actually higher than in adults and met the noninferiority criteria,” Healy said.

A global health threat

“[These findings show] that the MVA-BN vaccine is safe and well-tolerated in adolescents aged 12-17 years,” said Healy.

She noted that the results are particularly relevant to adolescents in the US and in regions where mpox is endemic, such as the Democratic Republic of Congo (DRC). Moreover, the risk of mpox-related morbidity and mortality is higher among children aged <8 years (especially in those aged <1 year), pregnant women, and immunosuppressed individuals. In the current DRC mpox outbreak, 70 percent of cases and 88 percent of deaths are in children aged <15 years.

“Evaluations in younger children are urgently needed to extend protection to the most vulnerable, particularly given the ongoing transmission among children in the DRC,” Healy said.