Rabies virus-based vaccines elicit neutralizing antibodies, poly-functional CD8+ T cell, and protect rhesus macaques from AIDS-like disease after SIV(mac251) challenge.
Highly attenuated rabies virus (RV) vaccine vectors were evaluated for their ability to protect against highly pathogenic SIV(mac251) challenge. Mamu-A*01 negative rhesus macaques were immunized in groups of four with either: RV expressing SIV(mac239)-GagPol, a combination of RV expressing SIV(mac239)-Env and RV expressing SIV(mac239)-GagPol, or with empty RV vectors. Eight weeks later animals received a booster immunization with a heterologous RV expressing the same antigens. At 12 weeks post-boost, all animals were challenged intravenously with 100 TCID(50) of pathogenic SIV(mac251-CX). Immunized macaques in both vaccine groups had 1.3-1.6-log-fold decrease in viral set point compared to control animals. The GagPol/Env immunized animals also had a significantly lower peak viral load. When compared to control animals following challenge, vaccinated macaques had a more rapid induction of SIV(mac251) neutralizing antibodies and of CD8(+) T cell responses to various SIV epitopes. Moreover, vaccinated macaques better maintained peripheral memory CD4(+) T cells and were able to mount a poly-functional CD8(+) T cell response in the mucosa. These findings indicate promise for RV-based vectors and have important implications for the development of an efficacious HIV vaccine.
Faul
Elizabeth J
EJ
Jefferson Vaccine Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Aye
Pyone P
PP
Papaneri
Amy B
AB
Pahar
Bapi
B
McGettigan
James P
JP
Schiro
Faith
F
Chervoneva
Inna
I
Montefiori
David C
DC
Lackner
Andrew A
AA
Schnell
Matthias J
MJ
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology*; D011820:Rabies virus / Q000276:immunology*; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology
D057134:Antibodies, Neutralizing; D018449:SAIDS Vaccines