Vaccine Protection of Rhesus Macaques Against Simian Immunodeficiency Virus Infection

Abstract

Rhesus macaques (Macaca mulatta) immunized with an inactivated whole SIVmac vaccine and muramyl dipeptide (MDP), incomplete Freund's adjuvant (IFA), or aqueous suspension were challenged intravenously with 0.1 TCID50 of cell-free SIVmac. Whereas virus was readily recovered from the peripheral blood lymphocytes of 10 of 10 nonvaccinated controls following this challenge dose, virus was not recovered from the three animals that received the vaccine with MDP nor from one of two animals that received the vaccine with IFA and one of three animals that received the aqueous vaccine. The animals that were protected against challenge were those that had detectable SIV antibody response to the envelop, both the outer glycoprotein (gp120) and the truncated transmembrane glycoprotein (gp31). Protected monkeys tended to have higher titers of syncytial inhibition antibody prior to challenge. An anamnestic response after challenge was observed only in the vaccinated monkeys that became infected. Vaccinated animals that became challenge-infected tended to live longer than infected controls. These results confirm those at two other primate centers and indicate that killed whole SIV vaccines can protect against low challenge doses of SIV and prevent early death in those monkeys that do become infected. The mechanism of this protection remains undetermined. This finding adds optimism to the possibility of an eventual AIDS vaccine.

Molecular and biological characterization of simian immunodeficiency virus macaque strain 32H proviral clones containing nef size variants

“…However, since human immunodeficiency virus (HIV) is highly variable and there is evidence that this antigenic variation may be driven by immune responses, studies using cloned virus and subunit vaccines from the same clone are essential in order to determine whether a subunit vaccine approach will successfully prevent infection with a completely homologous virus challenge. As simian immunodeficiency virus (SIV) is the closest relative of HIV-1 and HIV-2 (Hirsch et al, 1987;Franchini et al, 1987;Chakrabarti et al, 1987;Guyader et al, 1987), the rhesus macaque animal model has been used in many of the vaccine trials to date (Carlson et at., 1990;Desrosiers et at., I989;Johnson et aL, 1992;Marthas et al, 1990;Murphey-Corb et al, t989;Cranage IP: 54.202.233.140 On: Sun, 13 May 2018 06:24:58 530 E. W. Rud and others et al, 1992). Assessment of the protection induced in these studies was complicated because both the inactivated whole virus vaccines and challenge virus were produced on human cells and that even formalin-fixed uninfected human cells can protect a proportion of vaccines under these conditions (Stott et al, 1991).…”

Genital secretory immune response to chronic simian immunodeficiency virus (SIV) infection: a comparison between intravenously and genitally inoculated rhesus macaques

“…Macaques inoculated with whole-killed SIV vaccines develop strong serum antibody responses and are protected from i.v. challenge with a low dose of pathogenic cell-free SIV [23][24][25]. Thus, it appears that it may be possible to develop a vaeeine that will protect against i.v.…”

Potential significance of the cellular immune response against the macaque strain of simian immunodeficiency virus (SIVMAC) in immunized and infected rhesus macaques

“…The best established animal model for vaccine studies are macaques infectable with SIV or HIV-2 (Putkonen et al, 1989;Dormont et al, 1989;Stahl-Hennig et al, 1990). Protection against SIV or HIV-2 infection by immunization with formalininactivated (Desrosiers et al, 1989;Murphey-Corb et al, 1989;Carlson et aL, 1990) or detergent-treated virus (Desrosiers et al, 1989;Putkonen et aL, 1991;StahlHennig et al, 1992) can be achieved reproducibly, but so far there is no parameter available which predicts protection in the animals.…”