Background: Mycobacterium tuberculosis (MTB) Ag85A has become a component of multiple new tuberculosis vaccines. It is necessary to evaluate the immunogenicity, biological distribution, and safety of ag85a plasmid DNA (pDNA) to lay the foundation for the design of new vaccines.
Method: Chronic toxicity test: cynomolgus monkeys were injected intramuscularly with different doses of ag85a pDNA, and the vaccine absorption kinetics, tissue distribution, and toxicity were observed. Their immune function was evaluated. Acute toxicity test: Mice were injected intramuscularly 0.5 ml saline, and injected intramuscularly and intravenously 0.5 mg/0.5 ml ag85a pDNAs, respectively. The toxicity and death of the mice were observed continuously for 14 days. Allergic test: Guinea pigs were intraperitoneally injected with different doses of ag85a pDNA. After stimulation, the allergic reaction and its severity were observed.
Results: Chronic and acute toxicity tests demonstrated that ag85a pDNA injections caused no clinical symptoms or tissue damage. Repeated intramuscular injections in cynomolgus monkeys enhanced specific Th1 immune responses, with pDNA rapidly entering the bloodstream and its concentration positively correlating with dosage. After 8 weeks, ag85a gene was detected only in muscles, myocardium, iliac lymph nodes, and blood. Guinea pig allergy tests showed no weight changes or allergic reactions, even after multiple sensitizations.
Conclusions: The ag85a pDNA showed good safety in cynomolgus monkeys, mice, and guinea pigs, and induced high levels of antibodies and T-cell responses, making it a candidate antigen for the construction of a new tuberculosis vaccine.
Keywords: Ag85a plasmid DNA; Biodistribution; Immunogenicity; Mycobacterium tuberculosis; Safety evaluation.
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