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Mpox vaccination with a two-shot, low-dose intradermal approach produced similar antibody titers levels compared with the standard subcutaneous dosing regimen, an observational study showed.

Two 0.1-mL intradermal doses of the modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine yielded geometric mean titers of immunoglobulin G (IgG) antibodies that neutralize mpox of 88.65 (95% CI 48.09-163.42), compared with 103.72 (95% CI 48.62-221.29) after two standard 0.5-mL subcutaneous doses.

The study also found no difference in the magnitude of the immune response between recipients who were HIV-positive and those who were HIV-negative, Angelica Kottkamp, MD, from NYU Langone Health in New York City, and colleagues reported in a correspondence.

"We've been holding our breath for over a year, hoping that was the right decision" to adopt the low-dose intradermal regimen, commented Shira Doron, MD, chief infection control officer for Tufts Medicine in Boston.

During the initial mpox outbreak in the U.S., standard dosing was the rule. "But pretty quickly it became clear that we needed to [vaccinate] faster and the supply wasn't going to be there, so we had to switch to the lower dose with the intradermal approach," Doron explained.

The FDA approved regimen for the MVA-BN vaccine is 0.5 mL administered subcutaneously in a series of two doses given 28 days apart. However, an emergency use authorization was issued in August 2022 to allow intradermal administration of the vaccine with an injection volume of 0.1 mL. This became the preferred regimen because it had the potential to increase fivefold the number of available vaccine doses at a time when there was substantial uncertainty about vaccine availability.

To study the impact, Kottkamp's group analysed data from the New York City Observational Study of Mpox Immunity (NYC OSMI), which enrolled 145 participants without previous mpox infection but who were receiving the MVA-BN vaccine intradermally, subcutaneously, or a combination thereof. Among enrollees, 24% were living with HIV and 20% had received previous vaccination for smallpox. Nearly 90% identified themselves as LGBTQ+, of whom 85% were men.

In people with HIV infection, CD4+ counts were positively associated with IgG titers that point to virus neutralization.

"It was a good surprise to find out that people with well-controlled HIV (with CD4+ cell counts above 200) are able to develop similar antibodies [as] people without HIV. This is an important message as this patient population has been more vulnerable to mpox," Kottkamp told MedPage Today in an email interview.

However, getting a single dose of the MVA-BN vaccine was far less effective at eliciting an immune response than were two doses. People fully vaccinated with two doses had geometric mean IgG titers four times higher than those who only received one dose of the vaccine (199.4 vs 49.6).

"This study demonstrated the importance of receiving the full two-dose schedule of the mpox vaccine, especially in people with HIV -- which is a population that has been understudied in the context of this vaccine and clinically the most vulnerable population in terms of having higher mortality and severity of the disease," Kottkamp said.

Another notable finding of the study was that participants who had received previous smallpox vaccination as part of routine childhood vaccination programs had a higher level of IgG durability through 3 months after the second dose of the MVA-BN vaccine. "We were surprised to see that the antibody half-life, or median duration, was a little over 3 months in people without prior smallpox vaccination," Kottkamp said. "This finding needs to be explored further as [the] implication for long-term protection remains uncertain, which is important given still ongoing outbreaks of mpox."

A resurgence in November of mpox in the Democratic Republic of the Congo (DRC) has the potential to expand beyond Africa. As recently as December 7, the CDC issued a health advisory to physicians about the occurrence, geographic spread, and sex-related human-to-human transmission of the clade I subtype of the virus. It urged clinicians to be alert for cases in persons traveling from the DRC.

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