Study reveals waning antibody response to monkeypox vaccine over time

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New research to be presented at this year's European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024) in Barcelona, Spain (27-30 April) shows that the antibodies produced by Modified Vaccinia virus Ankara - Bavarian Nordic (MVA-BN) vaccination against mpox wane significantly within a year of receiving the vaccination – but in people with pre-existing immunity due to childhood smallpox vaccination in childhood, antibody levels remain high in almost all cases. The study is presented by PhD student Dr. Marc Shamier, Erasmus MC, Rotterdam, Netherlands, from a research team led by Dr Rory de Vries.

During the 2022-2023 mpox outbreak, MVA-BN was rapidly deployed among at-risk populations, including gay, bisexual, and other men who have sex with men (GBMSM). This vaccine is based on a highly attenuated strain of Vaccinia virus (VACV) – a virus that belongs to the orthopoxvirus genus, as do the viruses that cause smallpox (variola virus) and Mpox (monkeypox virus).

Little is known about the longevity of immune responses induced by-MVA-BN vaccination and the impact of prior smallpox vaccination. In this study, the authors assessed the antibody levels response to MVA-BN one year after vaccination. While marketed under various names such as JYNNEOS, IMVANEX, and IMVAMUNE, all are brand names for the same Modified Vaccinia Ankara (MVA)-based vaccine. As such, the immunological effects they confer are expected to be consistent across these products.

Out of the 118 vaccine recipients, 36 (30%) returned for the 1-year follow-up visit. Among individuals without pre-existing immunity, 14/21 (67%) had undetectable levels of VACV IgG and a 10.7-fold decrease in VACV IgG GMT (geometric mean, a standard measurement for antibody levels) was observed compared to the last time point after vaccination in 2022 (4 weeks after the second dose) (Figure 1 full abstract).

In contrast, among individuals with childhood smallpox vaccination, only one participant out of 15 (7%) had undetectable VACV IgG after one year, and the GMT reduction between 4 weeks after the last vaccine dose in 2022 and the one-year follow-up visit was 2.5-fold for those vaccinated with two doses of MVA-BN, and 1.9-fold for those vaccinated with one dose of MVA-BN.

The authors say: "A rapid decline in VACV-specific IgG antibodies was observed one year after MVA-BN vaccination, leading to loss of detectable antibodies in 42% (15/36) of the participants. This reduction was most pronounced in individuals without pre-existing immunity. As the mechanism of protection for mpox remains undefined, the implications of waning antibody levels for conferring protection remain uncertain."

The authors suggest that the decrease in antibodies over time following MVA-BN vaccination may be attributable its composition. They say: "The first and second-generation smallpox vaccines contained replication-competent vaccinia virus. MVA-BN is based on non-replicating virus, which may impact the strength and duration of the immune response; with the advantage of a low risk of side effects."

They add: "Regarding the potential necessity for a booster, it is premature to draw such conclusions. It is unclear how waning antibody levels relate to protection. Immunity also involves other elements, such as T-cell responses. Comprehensive clinical monitoring over time, which connects infection rates with antibody levels, is required to make informed decisions about booster vaccination protocols."


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