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
Nf. Rose et al., 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, J VIROLOGY, 74(23), 2000, pp. 10903-10910
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.