Potent, protective anti-HIV immune responses generated by bimodal HIV envelope DNA plus protein vaccination.
It is generally thought that an effective vaccine to prevent HIV-1 infection should elicit both strong neutralizing antibody and cytotoxic T lymphocyte responses. We recently demonstrated that potent, boostable, long-lived HIV-1 envelope (Env)-specific cytotoxic T lymphocyte responses can be elicited in rhesus monkeys using plasmid-encoded HIV-1 env DNA as the immunogen. In the present study, we show that the addition of HIV-1 Env protein to this regimen as a boosting immunogen generates a high titer neutralizing antibody response in this nonhuman primate species. Moreover, we demonstrate in a pilot study that immunization with HIV-1 env DNA (multiple doses) followed by a final immunization with HIV-1 env DNA plus HIV-1 Env protein (env gene from HXBc2 clone of HIV IIIB; Env protein from parental HIV IIIB) completely protects monkeys from infection after i.v. challenge with a chimeric virus expressing HIV-1 env (HXBc2) on a simian immmunodeficiency virusmac backbone (SHIV-HXBc2). The potent immunity and protection seen in these pilot experiments suggest that a DNA prime/DNA plus protein boost regimen warrants active investigation as a vaccine strategy to prevent HIV-1 infection.
Letvin
N L
NL
Harvard Medical School, Beth Israel Hospital, Boston, MA 02215, USA.
Montefiori
D C
DC
Yasutomi
Y
Y
Perry
H C
HC
Davies
M E
ME
Lekutis
C
C
Alroy
M
M
Freed
D C
DC
Lord
C I
CI
Handt
L K
LK
Liu
M A
MA
Shiver
J W
JW
D016915:AIDS Vaccines; D000818:Animals; D003602:Cytotoxicity, Immunologic; D004279:DNA, Viral / Q000008:administration & dosage* / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology*; D015752:Genes, env; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D000882:Haplorhini; D006801:Humans; D007114:Immunization; D016865:Reassortant Viruses / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D016915:AIDS Vaccines; D004279:DNA, Viral; D015686:Gene Products, env