Development of a single-shot subunit vaccine for HIV-1. 3. Effect of adjuvant and immunization schedule on the duration of the humoral immune response to recombinant MN gp120.
HIV-1 prophylaxis may require "sterilizing immunity" (i.e., the prevention of infection), and this is likely to demand a vaccine that gives high, long-lasting antibody titers. Although it is known that vaccine adjuvants and immunization schedule affect the magnitude of the immune response, there are few reports on antibody decay rates and persistence. Guinea pigs were immunized with recombinant gp120 using different adjuvants and immunization schedules, and the anti-gp120 and HIV-1 neutralization titers were determined over time following the last booster immunization. As observed previously in the literature, a longer time between boosting gave higher titers, with a slight increase in the decay half-life as the booster was spaced farther out from the primary immunization. The decay rate of the antibody titers showed surprisingly little effect of adjuvant, except for sustained-release polymer-based formulations. Adjuvants that gave high titers initially after boosting showed the greatest persistence of antibody titers (persistence defined as the residual titers at long times). These data show that high, long-lasting titers may be achieved by using sustained-release formulations, and these are likely the prime vaccine candidates for prophylaxis requiring prolonged sterilizing immunity.
Cleland
J L
JL
Department of Pharmaceutical Research, Genentech, Inc., South San Francisco, CA 94080, USA.
Barrón
L
L
Daugherty
A
A
Eastman
D
D
Kensil
C
C
Lim
A
A
Weissburg
R P
RP
Wrin
T
T
Vennari
J
J
Powell
M F
MF
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D003692:Delayed-Action Preparations; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007115:Immunization Schedule; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000008:administration & dosage*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D003692:Delayed-Action Preparations; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D014614:Vaccines, Synthetic