Chattopadhyay Anasuya, Park Steven, Delmas Guillaume, Suresh Rema, Senina Svetlana, Perlin David S, Rose John K
Department of Pathology, Yale University School of Medicine, 310 Cedar Street LH 315, New Haven, CT 06510, USA.
Vaccine. 2008 Nov 25;26(50):6329-37. doi: 10.1016/j.vaccine.2008.09.031. Epub 2008 Oct 1.
We have developed an experimental recombinant vesicular stomatitis virus (VSV) vectored plague vaccine expressing a secreted form of Yersinia pestis low calcium response protein V (LcrV) 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 the 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.
我们研发了一种实验性重组水疱性口炎病毒（VSV）载体鼠疫疫苗，该疫苗从VSV基因组的第一个位置开始表达鼠疫耶尔森菌低钙反应蛋白V（LcrV）的分泌形式。这种载体通过单剂量肌肉注射，可诱导产生高水平的针对LcrV的抗体滴度，并在小鼠中对肺鼠疫攻击提供90%-100%的保护。这种单剂量保护明显优于表达非分泌型LcrV蛋白的VSV所产生的保护。增强的保护作用与抗LcrV抗体增加以及偏向IgG2a且远离IgG1同种型有关。我们还发现，在攻击时CD4+细胞而非CD8+细胞的耗竭会导致疫苗保护作用降低，这表明细胞免疫在保护中发挥作用。
