Neither Whole Inactivated Virus Immunogen nor Passive Immunoglobulin Transfer Protects Against SIVagm Infection in the African Green Monkey Natural Host

Abstract

Attempts to protect against infection with simian immunodeficiency virus (SIV)mac grown in rhesus peripheral blood mononuclear cells (PBMCs) using whole inactivated virus immunogen or passive transfer of antibody have so far universally failed. However, such experiments have succeeded in the closely related human immunodeficiency virus (HIV)-2/cynomolgus system. To determine whether the failure in the SIVmac system is typical of primate lentiviruses we performed vaccination and passive transfer experiments using SIVagm (genetically distinct from SIVmac and HIV-2) in the natural African green monkey (AGM) host. To maximize the chances of success, both immunogen and challenge material were prepared using the molecular SIVagm3 clone. Two AGMs were immunized four times with whole inactivated SIVagm3 in RIBI adjuvant and two received intravenously a high dose of immunoglobulin (Ig) purified from a mixture of plasma from AGM, either naturally infected or infected with the homologous SIVagm3 clone. All were challenged with 20 median minimum infective doses of the SIVagm3 grown in AGM PBMCs and previously titrated in AGMs. Despite a strong humoral immune response in all monkeys at the time of challenge, including measurable neutralizing and antibody-dependent cell-mediated cytotoxicity antibodies, none were protected from infection.