In a recent study published in medRxiv * Preprint server, researchers evaluated the immunogenicity, safety, and booster efficacy of a modified Ankara-Northern Bavarian vaccinia virus (MVA-BN) currently used for immunization against monkeypox.
Monkeypox was first documented in West and Central Africa in the 1970s and 1980s. Over the past decade, emergency cases of monkeypox were reported from Africa until May 2022, when a large-scale outbreak led the World Health Organization (WHO) to declare a public health emergency of international concern.
Monkeypox virus belongs to Orthopox sex and related smallpox virus, which causes smallpox. Smallpox was eradicated by the 1970s using two generations of replication-based virus vaccines and a third-generation MVA vaccine. The MVA-BN vaccine is now being used to combat a worldwide outbreak of monkeypox.
Vaccines based on the replicated vaccinia virus have caused some potential adverse reactions, including vaccine for eczema, myocarditis, and postvaccine encephalitis, especially in immunocompromised individuals. The non-recurrent attenuated MVA vaccine had significantly fewer adverse reactions. Although the MVA vaccine has been shown to be effective in immunizing against monkeypox, there are no studies on its long-term immune response and enhanced efficacy.
In this study, the researchers conducted a preliminary clinical study to measure immune responses from one or two baseline doses of MVA-BN vaccine and compare it to the stinging response to a booster dose of MVA-BN in individuals who received a historical smallpox vaccine. . The follow-up clinical study was conducted 2 years later to investigate antibody persistence in vaccinated individuals in the first study.
In the initial study, individuals with neither a previous history of vaccination nor a vaccine scar were randomly divided into three groups. One group received one dose of MVA-BN and one dose of placebo four weeks later (1 x the MVA group). The second group received two doses of MVA-BN four weeks apart (2 × the MVA group), while the third group received two doses of placebo (the PBO group). The fourth group consisted of individuals who received the historical smallpox vaccine and who received a single booster dose of MVA-BN (HSPX).+ Collection). The immune responses of all individuals were assessed.
The follow-up study included participants re-screened from 1 × MVA, 2 × MVA, and HSPX+ groups. After their immunoreactivity was measured, the 1 × MVA and 2 × MVA groups were given an MVA-BN booster dose. Their humoral responses were measured at baseline and after one, two, four, and six weeks of the booster dose.
Humoral responses were measured using enzyme-linked immunosorbent assay (ELISA) and plaque reduction neutralization assay (PRNT). Cardiac changes and electrocardiogram (ECG) changes were monitored across vaccination groups to assess vaccine safety.
The results showed that the MVA-BN booster vaccine caused a similar increase in neutralizing antibodies in participants who received one or two primary vaccines, as well as individuals with previous immunity to smallpox.
Individuals given the initial MVA-BN vaccine showed an increase in neutralizing antibodies up to the fourth week. Participants who received two doses of the baseline vaccination had neutralizing antibody levels approximately 10 times those of the 1 × MVA group by the sixth week. For individuals previously vaccinated against smallpox, the MVA-BN booster dose neutralized antibody levels approximately four times those of individuals who received two base doses.
Neutralizing antibody levels six months after the last dose were higher than baseline in HSPX+ group, and detectable levels above baseline were also observed in the 1 × MVA and 2 × MVA groups.
Rapid antibody responses with neutralizing antibodies were observed in both 1 × MVA and 2 × MVA groups after the MVA-BN booster dose in the follow-up study. Serum titres were higher than those observed in the initial study and were comparable to those seen in HSPX.+ Post-reinforcement group. The humoral response remained elevated six months after the booster dose.
Adverse reactions to vaccinations were mild to moderate and did not lead to participants’ withdrawal from the study or death. The reactions commonly experienced were injection site pain, erythema, fatigue, headache, and myalgia.
Overall, the results showed that regardless of the history of previous smallpox vaccination or the number of initial vaccination doses, the MVA-BN booster dose elicits a robust immune response that persists above baseline levels for up to six months after the booster dose.
The immune memory of B cells without neutralizing antibodies indicates protection against viruses with long incubation times. Even a single initial vaccination dose can elicit a strong immune response to a booster dose two years later. Furthermore, the humoral response to the booster in individuals who received an initial dose, two base doses, and previous repeat smallpox vaccines did not produce any significant adverse reactions.
medRxiv publishes preliminary scientific reports that are not subject to peer review, and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.
- Heiko Eilchmann, Nathalie Sami, Daniela Richardt, Daria Schmidt, Jacqueline de Paul, Thomas B.H. Mayer, Gunter Silbernagel, Rick Nichols, Heinz Weidthaler, Lawrence de Morlos, Lady Chen, and Paul Chaplin. (2022). Single and dose vaccinations with MVA-BN® induce durable B-cell memory responses in healthy volunteers that are comparable to the older generation repeating smallpox vaccinations. medRxiv. bang: https://doi.org/10.1101/2022.09.07.22279689 https://www.medrxiv.org/content/10.1101/2022.09.07.22279689v1