mRNA Vaccines Against Bacteria
Despite most of the mRNA vaccine studies focusing on tumors and viruses, there are also mRNA vaccines applied to bacterial infection. Bacteria are a hundred times larger than viruses, and bacterial genomes are significantly bigger than viral genomes. There are high numbers of potential target antigens and a high level of antigenic variation in bacteria. Besides, most bacterial diseases have been treated with effective antibiotics, the cost of which is relatively low. At present, the amount of published work on mRNA vaccines against bacteria is limited. However, these studies provided some evidence that mRNA vaccine platform might be suitable to target bacterial pathogens, and suggest that mRNA vaccines against bacterial pathogens might be a potential solution to disease prevention.
mRNA vaccines against bacteria
For the development of bacterial vaccines, Mycobacterium tuberculosis (MTB) is one of the most important vaccine targets, as it infects a billion people worldwide. As early as 2010, a study used unmodified naked mRNA to be administered intranasally to elicit immune responses against MTB. The viability of this approach has been proved, as the bacterial loads in the lungs were controlled after four-week administration and there was a significant decrease of bacterial loads in mRNA-immunized mice compared to control animals.
Self-amplifying mRNA (SAM) vaccines against Streptococci
The self-amplifying mRNA (SAM) vaccine platform is based on the synthesis of self-amplifying mRNA formulated and delivered by lipid nanoparticles (LNPs) and other delivery systems. SAM vaccines represent a safe and versatile tool, which can induce robust innate and adaptive immune responses against a variety of viral antigens both in small animals and non-human primates. Researchers used SAM vaccine encoding antigens (streptolysin-O and pilus 2a backbone protein) from Group A (GAS) and Group B (GBS) Streptococci. Intramuscular administration of the SAM vaccines significantly stimulated the production of fully functional serum antibodies and induced partial protection in murine bacterial infection models.
SAM vaccines against chlamydia
Due to its relatively affordable and scalable, relatively long protein expression, and the stimulation of immunity against multivalent antigens, the SAM vaccine is well suited as a novel vaccine platform against chlamydia. Recent work has investigated the major outer membrane protein (MOMP)-encoding SAM complexed with cationic adjuvant formulations (CAFs) to target Chlamydia trachomatis. Researchers studied three SAM formulations and all of them showed antigen-specific humoral and cellular immunity against MOMP. In addition, they highlighted that CAFs are efficient delivery vehicles for SAM.
Effects of Cationic Adjuvant Formulation particle type, fluidity and immunomodulators on delivery and immunogenicity of saRNA. (Blakney, A. K., et al, 2019)
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- Maruggi, G., et al. (2017). "Immunogenicity and protective efficacy induced by self-amplifying mRNA vaccines encoding bacterial antigens."uo; Vaccine, 35(2), 361-368.
- Blakney, A. K., et al. (2019). "Effects of cationic adjuvant formulation particle type, fluidity and immunomodulators on delivery and immunogenicity of saRNA." Journal of Controlled Release, 304, 65-74.