Abstract
With the recent success of various viral-vectored vaccines against Ebola and SARS-CoV-2, the potential use of this type of vaccine platform in biosecurity against outbreak pathogens is established. Here we present the development of a novel adenoviral vectored vaccine against a bacterial disease, plague, caused by Yersinia pestis. Replication-deficient adenoviral vectored vaccines expressing two known protective Y. pestis antigens F1 and LcrV and combinations thereof were created. Expression of the antigens was confirmed in vitro, and immunogenicity assessed in mice. Protective efficacy was evaluated using a virulent Y. pestis aerosol challenge model in mice. All vaccine candidates induced high serum IgG antibody responses. Notably, the antibody responses were similar when vectors expressing different antigens were mixed or when using a single vector expressing a chimeric fusion of the two antigens. All of the six experimental vaccine formulations tested via intramuscular injection containing either the V gene or purified V protein provided 90%-100% protection from mortality due to inhalational infection with Y. pestis. Notably, only the Human adenovirus 5 construct expressing a full length F1-V fusion provided 100% protection from both morbidity and mortality after a single dose. In contrast, naïve mice and 50% of mice immunised with two doses of the recombinant proteins with adjuvant displayed clinical signs of illness (morbidity) despite protection from mortality. Based on these results, a ChAdOx1 full length F1-V fusion vaccine has progressed to phase I human clinical trials.
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An adenoviral-vectored vaccine expressing a fusion of key Yersinia pestis antigens confers robust protection against lethal aerosol plague in mice following a single dose. This work links antigen design and vector platform to protective immunity and supports clinical development of a gene-based countermeasure against pneumonic plague.