AttenuBlock for Optimized Immunity
The attenuation of a virus to produce a vaccine must balance reducing its virulence while retaining its ability to stimulate an effective immune response, or immunogenicity. Natural RSV infection does not stimulate a robust immune response, and immunity following SARS-CoV-2 infection wanes, so vaccine technologies that enhance immunogenicity are required. AttenuBlock is Meissa's proprietary platform that uses synthetic biology – the area of science focused on redesigning natural organisms to give them new abilities – to generate live attenuated RSV vaccine candidates designed to increase antigen expression and decrease or eliminate the expression genes that counteract the immune response.
Our AttenuBlock platform incorporates 10 years of research and development at Emory University, where researchers employed rational and precise codon deoptimization and other genetic strategies to produce hundreds of targeted mutations into the RSV genome, providing exquisite control over viral protein expression (Nature Communications, 2016).
In order to apply this platform to other targets in our pipeline, we replaced the RSV surface proteins with the SARS-CoV-2 Spike protein (see Figure below) or with the human metapneumovirus surface protein (not shown).
Meissa’s RSV and COVID-19 live attenuated vaccine candidates generated by synthetic biology have increased antigen expression (F protein for RSV and S protein for COVID-19) and decreased or eliminated expression of immune suppressors (SH and G proteins for RSV).
Codon Deoptimization for Live Attenuated Vaccine Candidates
The traditional processes for making live attenuated vaccines involve serial passage, gene deletions, or other mutation strategies. However, these strategies typically affect the viral replication machinery, which can compromise immunogenicity of the vaccine candidate. Meissa’s AttenuBlock platform incorporates codon deoptimization, which is used to reduce the efficiency of translating viral mRNA into proteins. By carefully selecting and replacing commonly used codons with nonpreferred codons in viral genes that inhibit the immune response, the translation of these viral mRNAs into proteins becomes inefficient. This approach results in heavy attenuation, optimized immunity, and genetic stability.
AttenuBlock uses codon deoptimization for highly attenuated, stable live vaccine candidates.
Vaccine Manufacturing for Global Supply
To meet global supply demand, Meissa is implementing straightforward, economical, and scalable vaccine manufacturing technologies. Meissa’s vaccine candidates grow well in cell culture to support manufacturing. Furthermore, Meissa’s single, low dose vaccine candidates allow for a smaller manufacturing footprint and fewer batches to support production.