Smallpox Vaccine LC16m8: Production, Properties, and Prospects

Abstract

Abrogation of obligatory vaccination against smallpox has lead to degradation of herd immunity and humanity has become vulnerable to long known infections, such as monkeypox (mpox), cowpox, camelpox, buffalopox and emerging ones, caused by viruses Alaska and Akhmeta. This situation demands availability of safe smallpox vaccines, the immunogenicity of which is comparable to vaccines used in the period of smallpox elimination. The aim of this review is to analyze the research of Japanese scientists on the production and investigation of properties of the smallpox vaccine LC16m8 and to assess further prospects for the use of the LC16m8 strain. The LC16m8 vaccine was obtained based on one of the Lister clones and has been licensed in Japan since 1975. Whole-genome sequencing revealed that its main difference from the genome of the original strain is a mutation in the B5R gene, which determines its safety for laboratory animals and humans. The immunogenicity of the vaccine based on this strain is comparable to the immunogenicity of the first generation vaccines: Lister, Dryvax, Ikeda. According to WHO recommendations, second generation vaccines ACAM 2000 and third generation vaccines based on the LC16m8 strain are reserve drugs. However, the established fact that the LC16m8 strain, when passaged in cell culture, spontaneously reverts to the original variant of the Lister strain led to genetic engineering work to delete the B5R gene to obtain the LC16m8Δ mutant, which is not capable of reversion. A vaccine based on the LC16m8Δ strain could technically be classified as a fourth generation drug, and taking into account the high immunogenicity and relative safety of this strain based on the results of preclinical studies, there is a real prospect of producing an advanced and effective reserve drug based on it. Thus, analysis of long-term data on the study of the LC16m8 vaccine indicates that this drug is superior to other analogues of the 1st, 2nd and 3rd generation in terms of effectiveness and safety. Further genetic engineering work with this strain, which made it possible to obtain a safe but immunogenic genovariant of the LC16m8Δ strain, is a clear example of a productive movement towards the development of safe and effective fourth generation vaccines.

Keywords

• vaccines against smallpox
• priming/boosting
• rate of seroconversion
• safety and immunogenicity