TY - JOUR
T1 - Targeting the vaginal mucosa with human papillomavirus pseudovirion vaccines delivering simian immunodeficiency virus DNA
AU - Gordon, Shari N.
AU - Kines, Rhonda C.
AU - Kutsyna, Galyna
AU - Ma, Zhong Min
AU - Hryniewicz, Anna
AU - Roberts, Jeffery N.
AU - Fenizia, Claudio
AU - Hidajat, Rachmat
AU - Brocca-Cofano, Egidio
AU - Cuburu, Nicolas
AU - Buck, Christopher B.
AU - Bernardo, Marcelino L.
AU - Robert-Guroff, Marjorie
AU - Miller, Chris J
AU - Graham, Barney S.
AU - Lowy, Douglas R.
AU - Schiller, John T.
AU - Franchini, Genoveffa
PY - 2012/1/15
Y1 - 2012/1/15
N2 - The majority of HIV infections occur via mucosal transmission. Vaccines that induce memory T and B cells in the female genital tract may prevent the establishment and systemic dissemination of HIV.We tested the immunogenicity of a vaccine that uses human papillomavirus (HPV)-based gene transfer vectors, also called pseudovirions (PsVs), to deliver SIV genes to the vaginal epithelium. Our findings demonstrate that this vaccine platform induces gene expression in the genital tract in both cynomolgus and rhesus macaques. Intravaginal vaccination with HPV16, HPV45, and HPV58 PsVs delivering SIV Gag DNA induced Gag-specific Abs in serum and the vaginal tract, and T cell responses in blood, vaginal mucosa, and draining lymph nodes that rapidly expanded following intravaginal exposure to SIV mac251. HPV PsV-based vehicles are immunogenic, which warrant further testing as vaccine candidates for HIV and may provide a useful model to evaluate the benefits and risks of inducing high levels of SIV-specific immune responses at mucosal sites prior to SIV infection.
AB - The majority of HIV infections occur via mucosal transmission. Vaccines that induce memory T and B cells in the female genital tract may prevent the establishment and systemic dissemination of HIV.We tested the immunogenicity of a vaccine that uses human papillomavirus (HPV)-based gene transfer vectors, also called pseudovirions (PsVs), to deliver SIV genes to the vaginal epithelium. Our findings demonstrate that this vaccine platform induces gene expression in the genital tract in both cynomolgus and rhesus macaques. Intravaginal vaccination with HPV16, HPV45, and HPV58 PsVs delivering SIV Gag DNA induced Gag-specific Abs in serum and the vaginal tract, and T cell responses in blood, vaginal mucosa, and draining lymph nodes that rapidly expanded following intravaginal exposure to SIV mac251. HPV PsV-based vehicles are immunogenic, which warrant further testing as vaccine candidates for HIV and may provide a useful model to evaluate the benefits and risks of inducing high levels of SIV-specific immune responses at mucosal sites prior to SIV infection.
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U2 - 10.4049/jimmunol.1101404
DO - 10.4049/jimmunol.1101404
M3 - Article
C2 - 22174446
AN - SCOPUS:84863418996
VL - 188
SP - 714
EP - 723
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -