Challenge of chimpanzees (Pan troglodytes) immunized with human immunodeficiency virus envelope glycoprotein gp120

Abstract

The human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome, infects humans and chimpanzees. To determine the efficacy of immunization for preventing infection, chimpanzees were immunized with gp120 purified from human T-cell lymphotrophic virus type IIIB (HTLV-IIIB)-infected cell membranes and challenged with the homologous virus, HTLV-IIIB. A challenge stock of HTLV-IIIB was prepared by using unconcentrated HTLV-IIIB produced in H9 cells. The titer of the virus from this stock on human and chimpanzee peripheral blood mononuclear cells and in human lymphoid cell lines was determined; a cell culture infectivity of 104 was assigned. All chimpanzees inoculated intravenously with 40 cell culture infectious units or more became infected, as demonstrated by virus isolation and seroconversion. One of two chimpanzees inoculated with 4 cell culture infectious units became infected. Chimpanzees immunized with gp120 formulated in alum developed antibodies which precipitated gpl20 and neutralized HTLV-IIIB. Peripheral blood mononuclear cells from gp120-vaccinated and HIV-infected animals showed a significantly greater response in proliferation assays with HIV proteins than did peripheral blood mononuclear cells from nonvaccinated and non-HIV-infected chimpanzees. Two of the gpl20-alum-immunized chimpanzees were challenged with virus from the HTLV-IIIB stock. One animal received 400 cell culture infectious units, and one received 40 infectious units. Both animals became infected with HIV, indicating that the immune response elicited by immunization with gpl20 formulated in alum was not effective in preventing infection with HIV-1. Acquired immunodeficiency syndrome is an immunopathological manifestation which occurs following infection by human immunodeficiency virus (HIV). Vaccines have proven to be the most effective means of controlling viral

Vaccine-induced protection of chimpanzees against infection by a heterologous human immunodeficiency virus type 1

“…This HIV-1 SF2 inoculum was equivalent to a primary isolate of HIV-1, as it had been passaged exclusively in human PBMC. It therefore more closely resembled viruses transmitted during natural HIV-1 infections than do cell lineadapted viruses, such as the HIV-1 LAI(IIIB) challenge stock used previously to test candidate HIV-1 vaccines in chimpanzees (2,6,7,17,22). The second experiment reported herein shows that immunization with envelope antigens from HIV-1 MN and/or HIV-1 LAI is sufficient to protect chimpanzees from infection with a heterologous primary isolate of HIV-1.…”

“…Virus was not isolated from any chimpanzee's PBMC obtained more than 6 weeks after inoculation of HIV-1 SF2 , suggesting very low virus burdens. In contrast, after infection with HIV-1 LAI or HIV-1 LAI(IIIB) , virus can be recovered consistently from most animals' PBMC for months and even years (2,6,7,(15)(16)(17)(18)22). In fact, isolation of HIV-1 from some chimpanzees infected with HIV-1 LAI for 6 or more years has been successful on more than 95% of attempts (14,15).…”

Isolation and characterization of a syncytium-inducing, macrophage/T-cell line-tropic human immunodeficiency virus type 1 isolate that readily infects chimpanzee cells in vitro and in vivo

“…In this study, we decided to screen fresh viral isolates from patients with AIDS for their ability to induce a rapid cytopathic infection in chimpanzee PBMC, a possible predictor of pathogenicity in vivo. Prior to initiating such a search, PBMC from several uninfected chimpanzees were pretested for susceptibility to an HIV-1 isolate, previously used for chimpanzee inoculations (HIV-1 IIIB040 [4]); the cells from one animal (ISIS no. 810) reproducibly yielded high titers of virus (approximately 10 5 TCID 50 /ml).…”

“…Inocula prepared from the molecularly cloned and highly tissue cultureadapted HIV-1 Lai (2, 49) and HIV-1 NL43 (1) replicated to low levels in chimpanzee PBMC. The HIV-1 chimpanzee challenge stock (HIV-1 IIIB-040 [4]) and an isolate (HIV-1 SG3.1 [31]) previously shown to be tropic for chimpanzee lymphocytes readily infected chimpanzee PBMC, although their replication kinetics were slower than those of HIV-1 DH12 and syncytium-forming activity in chimpanzee PBMC was difficult to detect (see below).…”

An infectious chimeric human immunodeficiency virus type 2 (HIV-2) expressing the HIV-1 principal neutralizing determinant

“…One obstacle in the development of vaccines against human immunodeficiency virus type 1 (HIV-1) infection has been the lack of animal models suitable for rapid, statistically meaningful, and inexpensive testing. Infection of a variety of nonhuman primates with HIV-1 has been reported, including chimpanzees (Pan troglodytes) (2), gibbons (Hylobates lar) (20), and macaques (Macaca nemestrina) (1,8). Unfortunately, the former two species are both endangered and expensive, all but prohibiting conclusive studies.…”