A safety and immunogenicity study of a novel subunit plague vaccine in cynomolgus macaques

Plague has led to millions of deaths in history and outbreaks continue to the present day. The efficacy limitations and safety concerns of the existing killed whole cell and live‐attenuated vaccines call for the development of new vaccines. In this study, we evaluated the immunogenicity and safety of a novel subunit plague vaccine, comprising native F1 antigen and recombinant V antigen. The cynomolgus macaques in low‐ and high‐dose vaccine groups were vaccinated at weeks 0, 2, 4 and 6, at dose levels of 15 μg F1 + 15 μg rV and 30 μg F1 + 30 μg rV respectively. Specific antibodies and interferon‐γ and interleukin‐2 expression in lymphocytes were measured. For safety, except for the general toxicity and local irritation, we made a systematic immunotoxicity study on the vaccine including immunostimulation, autoimmunity and anaphylactic reaction. The vaccine induced high levels of serum anti‐F1 and anti‐rV antibodies, and caused small increases of interferon‐γ and interleukin‐2 in monkeys. The vaccination led to a reversible increase in the number of peripheral blood eosinophils, the increases in serum IgE level in a few animals and histopathological change of granulomas at injection sites. The vaccine had no impact on general conditions, most clinical pathology parameters, percentages of T‐cell subsets, organ weights and gross pathology of treated monkeys and had passable local tolerance. The F1 + rV subunit plague vaccine can induce very strong humoral immunity and low level of cellular immunity in cynomolgus macaques and has a good safety profile. To investigate the immunogenicity and safety of a novel F1 + rV subunit plague vaccine, we conducted a repeated dose toxicity study in monkeys. The vaccine induced robust humoral immunity and low level of cellular immunity in monkeys. Vaccine led to a reversible increase in the number of peripheral blood eosinophils and the increases in serum IgE level in a few animals. Vaccination caused the histopathological change of granulomas at injection sites, but did not cause macroscopic signs of local irritation.