Study highlights the efficacy of MVA-BN booster vaccination in inducing durable B cell memory responses against monkeypox

In a recent study posted to the medRxiv* preprint server, researchers assessed the immunogenicity, safety, and booster-efficacy of the Modified Vaccinia virus Ankara-Bavarian Nordic (MVA-BN) vaccine currently being used for immunization against monkeypox.

Background

Monkeypox is a zoonotic disease first documented in Western and Central Africa in the 1970s and 1980s. Over the last decade, emergent cases of monkeypox were reported from Africa until May 2022, when a more widespread outbreak resulted in the World Health Organization (WHO) declaring it a public health emergency of international concern.

The monkeypox virus belongs to the Orthopoxvirus genus and is related to the Variola virus, which causes smallpox. Smallpox was eradicated by the 1970s using two generations of replicating vaccinia virus-based vaccines and the third generation MVA vaccine. The MVA-BN vaccine is now being used to combat the global monkeypox outbreak.

The replicating vaccinia virus-based vaccines caused some potentially adverse reactions, including eczema vaccinatum, myopericarditis, and post-vaccinal encephalitis, especially in immunocompromised individuals. The attenuated non-replicating MVA vaccine had substantially lower adverse reactions. Although the MVA vaccine has proven effective in immunization against monkeypox, studies on its long-term immune response and booster efficacy are lacking.

About the study

In the present study, the researchers conducted an initial clinical study to measure the immune responses elicited by one or two primary doses of the MVA-BN vaccine and compared it to the anamnestic response from a booster MVA-BN dose in individuals with historic smallpox vaccination. The follow-up clinical study was conducted after two years to investigate the antibody persistence in the individuals immunized in the first study.

In the initial study, individuals with no previous history of vaccination and no vaccinia scar were randomly divided into three groups. One group received one dose of MVA-BN and one dose of placebo four weeks later (1×MVA group). The second group received two doses of MVA-BN four weeks apart (2×MVA group), while the third group received two doses of placebo (PBO group). A fourth group consisted of individuals with historical smallpox vaccination who received a single booster MVA-BN dose (HSPX⁺ group). The immune responses of all the individuals were assessed.

The follow-up study included rescreened participants from the 1×MVA, 2×MVA, and HSPX⁺ groups. After measuring their immunogenicity, the 1×MVA and 2×MVA groups were administered an MVA-BN booster dose. Their humoral responses were measured at baseline and one, two, four, and six weeks after the booster dose.

The humoral responses were measured using enzyme-linked immunosorbent assay (ELISA) and plaque reduction neutralization test (PRNT). Cardiac changes and electrocardiogram (ECG) changes were monitored across vaccination groups to assess the safety of the vaccine.

Results

The results showed that the MVA-BN vaccine booster induced a comparable increase in neutralizing antibodies in participants with one and two primary vaccinations, as well as individuals with previous smallpox immunity.

Individuals who were given a single primary MVA-BN vaccination showed an increase in neutralizing antibodies till the fourth week. The participants who received two primary vaccination doses had neutralizing antibody levels almost 10 times that of the 1×MVA group by the sixth week. For previously smallpox immunized individuals, the booster MVA-BN dose neutralized antibody levels almost four times those of the individuals who received two primary doses.

The neutralizing antibody levels six months after the last dose was higher than baseline in the HSPX⁺ group, and detectable levels above baseline were also observed in the 1×MVA and 2×MVA groups.

Rapid anamnestic responses with neutralizing antibodies were observed in both 1×MVA and 2×MVA groups following the booster MVA-BN dose in the follow-up study. The serum titers were higher than those observed in the initial study and were comparable to those seen in the HSPX⁺ group post-booster. The humoral response remained elevated six months after the booster dose.

Adverse reactions to the vaccinations were all mild to moderate and did not result in participants withdrawing from the study or mortality. Commonly experienced reactions were injection site pain and erythema, fatigue, headache, and myalgia.

Conclusions

Overall, the results showed that regardless of previous smallpox vaccination history or the number of primary vaccination doses, the MVA-BN booster dose elicits a strong immune response sustained above baseline levels for up to six months after the booster.

B-cell immune memory without neutralizing antibodies indicates protection against viruses with long incubation periods. Even a single primary vaccination dose can elicit a robust immune response to a booster dose two years later. Furthermore, the humoral response to the booster in individuals with one and two primary doses and the earlier replicating smallpox vaccines resulted in no major adverse reactions.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information