Characterization of immune responses elicited in macaques immunized sequentially with chimeric VEE/SIN alphavirus replicon particles expressing SIVGag and/or HIVEnv and with recombinant HIVgp140Env protein.
In the present study, macaques were coimmunized with VEErep/SINenv chimeric alphavirus replicon particles expressing SIVp55Gag and HIVDeltaV2gp140Env or only with replicon particles expressing HIVDeltaV2gp140Env. All animals were subsequently immunized with recombinant trimeric HIVDeltaV2gp140Env protein. During alphavirus immunization, anti-SIVGag and anti-HIVEnv-specific interferon (IFN)-gamma responses, as well as high titers of anti-HIVEnv binding (gp120 but not gp41 specific) and anti-HIV neutralizing antibodies, were generated. The subsequent immunization with recombinant HIVDeltaV2gp140 enhanced the neutralizing antibody titers and Env-specific IFN-gamma responses. Following intravenous challenge with the R5- tropic SHIV(SF162P4) virus, significantly lower primary plasma viremia levels were recorded in the immunized animals, as compared to control animals immunized with replicon particles expressing influenza virus HA. Our results show that this method of immunization elicits both strong cellular immunity and neutralizing antibodies in primates and, thus, merits further investigation.
Xu
Rong
R
Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.
Srivastava
Indresh K
IK
Greer
Catherine E
CE
Zarkikh
Irina
I
Kraft
Zane
Z
Kuller
Larene
L
Polo
John M
JM
Barnett
Susan W
SW
Stamatatos
Leonidas
L
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics; D015686:Gene Products, env / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000096:biosynthesis*; D008253:Macaca mulatta; D011994:Recombinant Proteins / Q000276:immunology; D012093:Replicon; D012845:Sindbis Virus; D014614:Vaccines, Synthetic / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015483:HIV Antibodies; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; C115853:simian immunodeficiency virus gag p55