Single-dose virus-vectored vaccine protection against Yersinia pestis challenge: CD4+ cells are required at the time of challenge for optimal protection

摘要

We have developed an experimental recombinant vesicular stomatitis virus (VSV) vectored plague vaccine expressing a secreted form of Yersinia pestis LcrV protein from the first position of the VSV genome. This vector, given intramuscularly in a single dose, induced high-level antibody titers to LcrV and gave 90–100% protection against pneumonic plague challenge in mice. This single-dose protection was significantly better than that generated by VSV expressing the non–secreted LcrV protein. Increased protection correlated with increased anti-LcrV antibody and a bias toward IgG2a and away from IgG1 isotypes. We also found that depletion of CD4⁺ cells, but not CD8⁺ cells, at the time of challenge resulted in reduced vaccine protection, indicating a role for cellular immunity in protection.