Prevention of HIV-2 and SIVsm infection by passive immunization in cynomolgus monkeys

Abstract

Infection of macaques with simian immunodeficiency virus (SIV) and human immunodeficiency virus type 2 (HIV-2) are useful models for studies of immunotherapy and vaccination against HIV as well as for testing of antiviral drugs. Vaccine research showing protective immunity in immunized monkeys has indicated that it will be possible to develop a vaccine for prevention of human HIV infection, although many hurdles remain. The design of an HIV vaccine would be helped if the basis of the protective immunity could be elucidated. Passive immune prophylaxis offers a means to determine the relative role of antibodies in protection against infection. We have studied whether a transfer of antibodies can prevent HIV-2 and SIVsm (SIV of sooty mangabey origin) infection in cynomolgus monkeys. Sera with high antibody titres were collected, heat-treated and injected into naive animals 6 h before challenge with 10-100 monkey-infectious doses of live homologous virus. All control animals treated with normal monkey serum (n = 6) or no serum (n = 39) became infected by the challenge virus, whereas five out of seven animals pretreated with antibody-containing serum at a dose of 9 ml kg-1 resisted infection. Thus passively transferred antibodies can protect against a low-dose lentivirus challenge in a nonhuman primate.

Mechanisms of protection induced by attenuated simian immunodeficiency virus. I. Protection cannot be transferred with immune serum.

“…In contrast to the results obtained with SIVmne, SIVsm and HIV-2 (Lewis et al, 1993 ;Putkonen et al, 1991), where protection was successfully transferred, experiments with SIVmac have been uniformly unsuccessful (Gardner et al, 1995 ;Kent et al, 1994). In the first study, neither immune serum pools prepared from early acute (12 weeks) or chronically ( 2 years) infected macaques nor a mixture of four neutralizing anti-SIV MAbs detectably altered the course of infection in naive macaques, following challenge with a genetically closely related virus prepared on simian PBMC (Kent et al, 1994).…”

Induction of gp120-specific protective immune responses by genetic vaccination with linear polyethylenimine–plasmid complex

“…An optimal acquired immunodeficiency syndrome (AIDS) vaccine should be able to induce both envelope glycoprotein 120 (gp120)-specific neutralizing antibodies, as well as systemic and mucosal cellular immune responses to human immunodeficiency virus (HIV)-infected cells [1][2][3][4][5][6][7]. Vaccine strategies which elicit potent cytotoxic T cell (CTL) responses lead to reduced virus loads and long-term protection against immunodeficiency disease in macaque challenge studies using simian immunodeficiency virus (SIV) or pathogenic simian-human immunodeficiency virus chimeras (SHIV) [8,9].…”

The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1.

“…** In contrast, neutralization determinants on SIV have not been defined. Immunization with inactivated SIV confers protection against virus challenge (4-7), as does passive immunization of cynomolgus monkeys with high-titer immune sera (20). Thus, although antibody appears to be sufficient to confer protective immunity to SIV, the nature of this antibody-mediated protective immune response is unknown.…”