Recombinant vesicular stomatitis virus (rVSV) has been developed as a vector platform for a range of human pathogens (Finke and Conzelmann. Current Topics in Microbiology and Immunology. 2005, 292:165-200; Jones et al. Nature Medicine. 2005, 11(7):786-90; Kahn et al. Journal of Virology. 2001, 75(22):11079-87; Kapadia et al. Virology. 2005, 340(2):174-82; Reuter et al. Journal of Virology. 2002, 76(17):8900-9; Roberts et al. Journal of Virology. 1999, 73(5):3723-32; Roberts et al. J Virol. 1998, 72(6):4704-11; Rose et al. Cell. 2001, 106(5):539-49), and an optimized rVSV vector expressing HIV-1 gag protein has completed clinical evaluation (HVTN 090: accessible via the worldwide web at URL clinicaltrials.gov/). Despite these advances, challenges remain in the development of the rVSV vector platform, including potential immunity generated against vector proteins that may interfere with subsequent boosting immunizations with rVSV vectors. This potential problem may be overcome when rVSV vectors are used in heterologous prime-boost immunization regimens with other immunologically distinct vectors (Amara et al. Science. 2001, 292(5514):69-74; Amara et al. J Virol. 2002, 76(15):7625-31; Egan et al. AIDS Research and Human Retroviruses. 2005, 21(7):629-43; Hanke et al. J Virol. 1999, 73(9):7524-32; Ramsburg et al. Journal of Virology. 2004, 78(8):3930-40; Santa et al. J Virol. 2007; Xu et al. Journal of Virology. 2009, 83(19):9813-23). Serotype switching of rVSV vectors, achieved by swapping the surface G protein with that of a different vesiculovirus serotype, also enhances immunogenicity in prime-boost regimens in mice (Rose et al. Journal of Virology. 2000, 74(23):10903-10). However, cross-reactivity of cellular immune responses directed towards rVSV core proteins may limit this approach.
In view of these observations and potential limitations, there is a need for additional heterologous vectors for use either alone or in conjunction with rVSV vectors.
USPTO Backgrounds
USPTO Backgrounds