Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus.

Abstract

Sustained high titers of neutralizing antibodies were elicited in three chimpanzees after sequential injections of different human immunodeficiency virus 1 (HIV-1) antigen preparations derived from the HIV-1 BRU strain that included whole inactivated virus or purified recombinant proteins and then synthetic peptides identical to the major HIV-1 neutralizing epitope V3. The animals were chaflenged i.v. with 40 chimpanzee infectious doses (equivalent to 100 tissue culture 50% infectious doses) of a stock of HIV-1 IIIB isolate. After 6 mo of follow-up, all three animals appeared uninfected by serologic and virologic criteria, including polymerase chain reaction analysis and failure to isolate virus from peripheral blood lymphocytes, bone marrow, and lymph node tissue. Of two chimpanzees monitored for 1 yr, virus was isolated initially from one animal at 32 weeks, but the second chimpanzee was virus negative by all assays through 12 mo; the third animal has remained virus negative through 9 mo of follow-up. These results indicate that it is possible to elicit protection against, or significantly delay infection of, HIV-1 by immunization, thus laying the foundation for development of an HIV-1 vaccine.

HIV-189.6 Gag expressed from a replication competent HSV-1 vector elicits persistent cellular immune responses in mice

“…While this approach can prevent infections with viruses containing glycoproteins closely related to the original immunogen, it has failed to generate the broadly protective response required for a successful vaccine, given the diversity of circulating HIV clades [1][2][3][4][5][6]. The current strategy for development of a vaccine has shifted to presentation of a variety of HIV-1 recombinant proteins with novel delivery vectors and/or adjuvants to elicit T-cell mediated immunity (CMI) with an emphasis on cytotoxic CD8+ lymphocyte (CTL) responses.…”

Development of Vaccine Adjuvants: A Historical Perspective

“…The Syntax adjuvant formulation (SAF) [196] used the potent block copolymer L-121 to generate a squalane-in-water formulation. The SAF M formulation developed for manufacturing was shown to be effective in several primate systems [218][219][220]. Use of the nontoxic low-HLB spreading agent Span 85 [221] and Tween 80 as stabilizers for a squalene-water emulsion produced the adjuvant MF59 [222,223].…”

“…Extensive work has been done with an SAF squalane/L121 block copolymer system in conjunction with threonyl-MDP pioneered by Allison and Byars [260]. Preclinical effi cacy was demonstrated with a spectrum of antigens [261], including HIV in chimpanzees [220]. The squalene-water emulsion MF59 was tested with MTP-PE and HIV vaccines in a phase I clinical trial [262] and with infl uenza vaccine [263] where reactogenicity in the presence of MTP-PE was unacceptable.…”

Adjuvants for a New Generation of Vaccines

“…simian acquired immune deficiency syndrome (52). SIV (53) , and a recombinant HIV-1 vaccine in chimpanzees (54). In the absence of an efficacious adjuvant, little or no protection is observed.…”