No abstract

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.

The acidic basic repeat antigen (ABRA) of Plasmodium falciparum is a potential vaccine candidate against erythrocytic stages of malaria. We report, for the first time, the immunological characteristics of recombinant ABRA constructs. The recombinant proteins representing different fragments of ABRA were expressed in Escherichia coli, either as fusions with maltose binding protein or as 6X histidine tagged molecules, and purified by affinity chromatography. Immunogenicity studies with these constructs in rabbits and mice indicated that the N-terminal region is the least immunogenic part of ABRA. T-cell proliferation experiments in mice immunized with these constructs revealed that the T-cell epitopes were localized in the middle portion of the protein. More importantly, the purified immunoglobulin G specific to middle and C-terminal fragments prevented parasite growth at levels approaching 80-90%. We found that these proteins were also recognized by sera from P. falciparum-infected patients from Rourkela, a malaria endemic zone of India. Our immunogenicity results suggest that potential of ABRA as a vaccine candidate antigen should be investigated further.