Monkeypox Vaccine Antibody Response Declines Over Time

New findings set to be unveiled at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024) in Barcelona, Spain (27-30 April) reveal that the antibodies elicited by Modified Vaccinia virus Ankara – Bavarian Nordic (MVA-BN) vaccination against monkeypox diminish significantly within twelve months of inoculation – yet persist at elevated levels among individuals with pre-existing immunity due to childhood smallpox vaccination. The research, led by PhD candidate Dr. Marc Shamier of Erasmus MC, Rotterdam, Netherlands, under the guidance of Dr. Rory de Vries, sheds light on these developments.

During the 2022-2023 monkeypox outbreak, MVA-BN was swiftly administered among vulnerable populations, including gay, bisexual, and other men who have sex with men (GBMSM). This vaccine is derived from a highly attenuated strain of Vaccinia virus (VACV) – a member of the orthopoxvirus genus, akin to the viruses responsible for smallpox (variola virus) and monkeypox (monkeypox virus).

Limited knowledge exists concerning the durability of immune responses induced by MVA-BN vaccination and the influence of prior smallpox vaccination. The study in question evaluated the antibody response to MVA-BN one year post-vaccination. Although marketed under various names such as JYNNEOS, IMVANEX, and IMVAMUNE, all denote the same Modified Vaccinia Ankara (MVA)-based vaccine, thereby expected to confer consistent immunological effects.

Among the 118 vaccine recipients, only 36 (30%) attended the one-year follow-up visit. Among those lacking pre-existing immunity, 14 out of 21 (67%) exhibited undetectable levels of VACV IgG, with a 10.7-fold decline in VACV IgG GMT (geometric mean, a standard measure for antibody levels) compared to the levels observed in 2022 (4 weeks post-second dose) (Figure 1 full abstract).

Conversely, in individuals with childhood smallpox vaccination, merely one out of 15 participants (7%) had undetectable VACV IgG after one year. The reduction in GMT between 4 weeks post-last vaccine dose in 2022 and the one-year follow-up visit was 2.5-fold for individuals receiving two doses of MVA-BN and 1.9-fold for those receiving a single dose.

The researchers state: “A rapid decline in VACV-specific IgG antibodies occurred one year post-MVA-BN vaccination, resulting in undetectable antibodies in 42% (15/36) of participants. This decrease was most pronounced in individuals lacking pre-existing immunity. As the protective mechanism against monkeypox remains elusive, the implications of diminishing antibody levels for conferring protection remain uncertain.”

They propose that the decline in antibodies over time post-MVA-BN vaccination may be attributed to its composition. They explain: “First and second-generation smallpox vaccines contained replication-competent vaccinia virus. MVA-BN, however, is based on non-replicating virus, potentially impacting the strength and duration of the immune response, with the added advantage of minimal side effects.”

Furthermore, they remark: “As for the potential need for a booster, it is premature to draw definitive conclusions. The correlation between waning antibody levels and protection remains unclear. Immunity also involves other components, such as T-cell responses. Comprehensive longitudinal clinical monitoring, linking infection rates with antibody levels, is necessary to make informed decisions regarding booster vaccination strategies.”

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