Glycoprotein exchange vectors based on vesicular stomatitis virus allow effective boosting and generation of neutralizing antibodies to a primary isolate of human immunodeficiency virus type 1

Live recombinant vesicular stomatitis viruses (VSVs) expressing foreign ant igens are highly effective vaccine vectors. However, these vectors induce h igh-titer neutralizing antibody directed at the single VSV glycoprotein (G) , and this antibody alone can prevent reinfection and boosting with the sam e vector. To determine if efficient boosting could be achieved by changing the G protein of the vector, we have developed two new recombinant VSV vect ors based on the VSV Indiana serotype but with the G protein gene replaced with G genes from two other VSV serotypes, New Jersey and Chandipura. These G protein exchange vectors grew to titers equivalent to wild-type VSV and induced similar neutralizing titers to themselves but no cross-neutralizing antibodies to the other two serotypes. The effectiveness of these recombin ant VSV vectors was illustrated in experiments in which sequential boosting of mice with the three vectors, all encoding the same primary human immuno deficiency virus (HM envelope protein, gave a fourfold increase in antibody titer to an oligomeric HIV envelope compared with the response in animals receiving the same vector three times. In addition, only the animals booste d with the exchange vectors produced antibodies neutralizing the autologous HIV primary isolate. These VSV envelope exchange vectors have potential as vaccines in immunizations when boosting of immune responses may be essenti al.