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 getting used for immunization against monkeypox.

Study: Single and 2-dose vaccinations with MVA-BN® induce durable B cell memory responses in healthy volunteers which might be comparable to older generation replicating smallpox vaccines. Image Credit: MIA Studio/Shutterstock

Background

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

The monkeypox virus belongs to the Orthopoxvirus genus and is said to the Variola virus, which causes smallpox. Smallpox was eradicated by the Nineteen Seventies using two generations of replicating vaccinia virus-based vaccines and the third generation MVA vaccine. The MVA-BN vaccine is now getting used to combat the worldwide monkeypox outbreak.

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

Concerning the study

In the current 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 research the antibody persistence within the individuals immunized in the primary study.

Within 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 4 weeks later (1×MVA group). The second group received two doses of MVA-BN 4 weeks apart (2×MVA group), while the third group received two doses of placebo (PBO group). A fourth group consisted of people with historical smallpox vaccination who received a single booster MVA-BN dose (HSPX+ group). The immune responses of all of 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 a pair of×MVA groups were administered an MVA-BN booster dose. Their humoral responses were measured at baseline and one, two, 4, and 6 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 evaluate the protection of the vaccine.

Results

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

Individuals who got a single primary MVA-BN vaccination showed a rise 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 4 times those of the individuals who received two primary doses.

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

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

Antagonistic reactions to the vaccinations were all mild to moderate and didn’t lead to participants withdrawing from the study or mortality. Commonly experienced reactions were injection site pain and erythema, fatigue, headache, and myalgia.

Conclusions

Overall, the outcomes showed that no matter previous smallpox vaccination history or the variety of primary vaccination doses, the MVA-BN booster dose elicits a robust immune response sustained above baseline levels for as much as 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 strong immune response to a booster dose two years later. Moreover, the humoral response to the booster in individuals with one and two primary doses and the sooner replicating smallpox vaccines resulted in no major antagonistic reactions.

*Vital notice

medRxiv publishes preliminary scientific reports that aren’t peer-reviewed and, due to this fact, mustn’t be thought to be conclusive, guide clinical practice/health-related behavior, or treated as established information

Journal reference:

• Heiko Ilchmann, Nathaly Samy, Daniela Reichhardt, Darja Schmidt, Jacqueline D Powell, Thomas PH Meyer, Günter Silbernagl, Rick Nichols, Heinz Weidenthaler, Laurence De Moerlooze, Liddy Chen, and Paul Chaplin. (2022). Single and 2-dose vaccinations with MVA-BN® induce durable B cell memory responses in healthy volunteers which might be comparable to older generation replicating smallpox vaccines. medRxiv. doi: https://doi.org/10.1101/2022.09.07.22279689 https://www.medrxiv.org/content/10.1101/2022.09.07.22279689v1