A recent article published in the journal Vaccine describes the results of a phase III clinical trial that showed consistent immunogenicity for a freeze-dried (FD) formulation of Bavarian Nordic’s Modified Vaccinia Ankara (MVA-BN). More specifically, statistically equivalent neutralizing antibody titers were observed after the second vaccine dose with comparable safety and reactogenicity; therefore, these vaccines may offer a good alternative to liquid-frozen vaccines.
Study: A randomized phase 3 trial to assess the immunogenicity and safety of 3 consecutively produced lots of freeze-dried MVA-BN® vaccine in healthy adults. Image Credit: Maryna Trusava / Shutterstock.com
Vaccine storage and handling are integral to the success of global vaccination programs. An appropriate vaccine storage facility is also necessary to ensure the effectiveness and tolerability of vaccines.
The strategic use and stockpiling of orthopoxvirus vaccines are of great importance to public health, as vaccination remains the only effective protection against orthopoxvirus-induced diseases, such as smallpox and mpox.
The use of the smallpox vaccine remains highly relevant because human mpox infections appear to have increased over the past decade, with the potential for human-to-human spread. One smallpox vaccine by Bavarian Nordic A/S is based on the highly attenuated and modified vaccinia Ankara strain (MVA-BN).
The MVA-BN liquid-frozen formulation has been approved for use in European adults to prevent smallpox and mpox disease. This vaccine has also been approved in the United States for the prevention of smallpox and mpox disease in adults at high risk of infection and in Canada for the prevention of smallpox, mpox, and related orthopoxvirus infections and illnesses.
To enhance the long-term storage and distribution of smallpox vaccine stockpiles, an FD formulation of the MVA-BN vaccine was developed. In contrast to the licensed liquid-frozen formulation of the MVA-BN smallpox vaccine, the FD formulation offers greater storage flexibility and shelf life.
In previous studies with MVA-BN, lyophilized and liquid-frozen formulations provided equivalent immune responses and safety characteristics. The current study examines the long-term stability of the FD formulation (FD-MVA-BN).
About the study
The current phase III double-blinded, multicenter randomized trial examined the immunogenicity and safety of three consecutive lots of the FD-MVA-BN vaccine. This study involved random assignments of 1,129 healthy adults into three treatment groups, with each subject receiving two immunizations four weeks apart.
To determine the vaccine’s consistency, total and neutralizing antibody titers, seroconversion rates, the ratio or consistency of geometric mean titers (GMTs) between group lot pairings, and correlation analysis between total and neutralizing antibody titers were used.
As part of the safety assessment, solicited and unsolicited adverse events were used to determine the overall safety and reactogenicity of FD-MVA-BN.
There was no statistically significant difference in the neutralizing antibody titers among groups following three consecutive doses of FD-MVA-BN two weeks after receipt of the last vaccination dose. Meanwhile, the seroconversion ranged from 99.1-99.7%, with the immunogenicity results consistent between the lots.
MVA-BN was found to produce maximal humoral responses two weeks following the second vaccine dose. The present trial consistently showed peak antibody titers in the 3 log10 range that protected against infection.
Similarly, FD-MVA-BN vaccination consistently generated strong antibody titers across numerous batches manufactured, thus supporting the hypothesis that lyophilization does not affect the vaccine’s immunogenicity.
The current study also validated the safety profile of this vaccine by demonstrating a lack of any significant vaccine-related side effects. Additionally, cardiac inflammatory issues were absent in volunteers inoculated with the FD-MVA-BN as opposed to those detected after replicating smallpox vaccines.
The most frequently reported adverse effects following FD MVA-BN treatment were local and general reactions of mild-to-moderate intensity that were self-limiting in nature. These incidents’ frequency, intensity, and duration were also evenly distributed among the three lots. In addition, adverse effects did not appear to be clustered across all lot groups.
The reactogenicity and immunogenicity of the vaccine were consistent throughout all production batches.
FD-MVA-BN elicited consistent immunogenicity with statistically equal neutralizing antibody titers two weeks following the second vaccine dose across multiple lot groups. Furthermore, FD-MVA-BN was found to be safe and reactogenic across lot groups, consistent with MVA-established BN’s safety profile.
Taken together, the study findings indicate that the FD-MVA-BN vaccine could serve as a potential alternative to the liquid-frozen formulation due to the reliability of its production processes, long-term stability, and minimal dependence on cold-chain transport.
- Turner Overton, E., Schmidt, D., et al. (2022). A randomized phase 3 trial to assess the immunogenicity and safety of 3 consecutively produced lots of freeze-dried MVA-BN® vaccine in healthy adults. Vaccine. doi:10.1016/j.vaccine.2022.10.056