Exploring immunogenicity, boosting efficacy and safety of modified vaccinia Ankara-Bavarian Nordic vaccine

By Pooja Toshniwal PahariaReviewed by Aimee MolineuxDec 7 2022

In a recent study published in The Journal of Infectious Diseases, researchers evaluated the immunogenicity, boosting efficacy, and safety of single-dose and two-dose MVA-BN (modified vaccinia Ankara-Bavarian Nordic) vaccinations in comparison to replicating smallpox vaccines.

MVA-BN vaccination is a highly attenuated, purified, live vaccine approved for the prevention of monkeypox and smallpox. It confers humoral immune protection to a similar extent as conventional smallpox vaccines. In addition, MVA-BN has been reported safe for use in healthy adults, individuals with HIV (human immunodeficiency virus) infections, HSCT (hematopoietic stem cell transplantation) history, and those with exfoliative dermatological diseases. However, data on the long-term protective immunity conferred by and booster dose effects of MVA-BN vaccines are limited.

About the study

In the present study, researchers evaluated single-dose and two-dose MVA-BN vaccine immunogenicity, boosting efficacy and safety compared to replicating smallpox vaccines between 2006 and 2009 at a European location.

The first study was a double-blinded, phase 2, non-inferiority, placebo-controlled, partially randomized clinical trial. Individuals lacking smallpox vaccination history (HSPX-) were 1:1:1 randomized to be vaccinated 28 days apart with one MVA-BN vaccine dose and one placebo dose (one-dose MVA), two MVA-BN vaccine doses (two-dose MVA), or two tris buffer placebo (PBO) doses.

Individuals with a history of smallpox vaccinations (HSPX+) received one booster dose (BD) of the MVA-BN vaccine. The immunogenicity analysis's prime objective was to evaluate the immune responses among HSPX+ and two-dose MVA-BN group individuals to investigate whether a single MVA-BN BD in previously vaccinated persons could induce similar humoral responses as two-dose prime MVA-BN vaccinations in individuals who did not receive any smallpox vaccines.

The second (or follow-up) analysis was an open-label phase 2 clinical trial conducted to assess immune responses among one-dose MVA-BN vaccinees, two-dose MVA-BN vaccinees, and HSPX+ individuals after two years of their previous dose administered during the first study. In addition, MVA-BN BD was administered to an HSPX- individual subset (one-dose MVA BD vaccinees and two-dose MVA BD vaccinees) for evaluating post-booster safety and immunogenicity.

The first study comprised healthy males and non-pregnant females aged between 18 years and 55 years with normal laboratory test reports at screening. The one-dose MVA-BN, two-dose MVA-BN, and PBO vaccinees were not vaccinated with any smallpox vaccines and had no identifiable vaccinia scar. MVA-BN vaccines were administered subcutaneously at ≥ 0.50 x 10⁸ tissue culture infectious dose (TCID₅₀) MVA-BN doses. ELISA (enzyme-linked immunosorbent assays) and PRNT (plaque reduction neutralization tests) were performed to measure serological neutralizing antibodies (nAb) and total antibody titers.

The first study specimens were obtained at screening and after two weeks, four weeks, six weeks, eight weeks, and six months following the most recent vaccination. The second study specimens were obtained two years after the first vaccination. Boosted individual blood specimens were obtained after one week, two weeks, four weeks, and six months of boosting. Safety assessments comprised solicited and unsolicited local-level and systemic-level AEs (adverse events) and serious AEs (SAEs). AEs were documented for eight post-booster days, and safety evaluations were conducted during screening and 14 days post-booster vaccinations.

Results

The first study comprised 753 individuals, of which 204 and 549 were HSPX+ and HSPX- individuals, respectively. HSPX- individuals were randomized to receive one-dose MVA, two-dose MVA, and PBO vaccines. Eight individuals were considered non-eligible and, therefore, excluded from the analysis. As a result, 745 individuals were considered for the final analysis, of which 181, 183, and 181 received one-dose MVA-BN, two-dose MVA-BN, and PBO vaccines, respectively, respectively and 200 HSPX+ individuals received MVA-BN BD.

After nearly two years, 304 individuals (91 and 92 from one-dose MVA-BN and two-dose MVA-BN vaccinees, respectively) and 121 HSPX+ individuals provided specimens for humoral protection assessments. In total, 77 one-dose MVA-BN vaccinees and 75 two-dose MVA-BN vaccinees, respectively, received MVA-BN BD.

Most of the individuals were Caucasian women, and HSPX+ individuals were elder (average age 42 years) compared to other group individuals (average age 25 to 26 years). During the first study, 64% of individuals received simultaneous medications, and most of them were prescribed analgesic and oral contraceptive medications. The second study participants had similar demographic features.

The nAb geometric mean titers (GMTs) enhanced from 1.1 (at baseline among non-smallpox vaccinees) to 7.2 and 7.5 in four weeks among one-dose MVA-BN and two-dose MVA-BN vaccinees, respectively). Two weeks later, the titers increased to 46 among two-dose MVA-BN vaccinees. Among HSPX+ individuals, nAb GMTs elevated rapidly from 22 to 175 within two weeks. Two years later, GMT values among one-dose MVA-BN vaccinees, two-dose MVA-BN vaccines, and HSPX+ individuals were 1.1, 1.3, and 10, respectively.

Post-boosting priorly naïve individuals, nAb GMTs rapidly increased within 14 days to 81 and 125 in one-dose MVA-BN vaccinees and two-dose MVA-BN vaccines, greater than those observed post-prime MBA-BN vaccination and similar to those observed among boosted HSPX+ MVA-BN BD recipients. After six months of booster vaccinations, GMT values of 26 and 49 were observed among one-dose MVA-BN vaccinees and two-dose MVA-BN vaccinees, respectively. No safety issues were identified.

Overall, the study findings showed that MVA-BN BD induced robust immunological responses irrespective of history of smallpox vaccinations and one- or two-dose prime MVA-BN vaccinations.