Protection of Cynomolgus Macaques ( Macaca fascicularis ) Against Infection with the Human Immunodeficiency Virus Type 2 Strain ben (HIV-2ben) by Immunization with the Virion-Derived Envelope Glycoprotein gp130

Abstract

We have investigated the efficiency of a subunit vaccine consisting of native gp130 micelles of HIV-2ben mixed with keyhole limpet hemocyanin (KLH). Over a period of 52 weeks, nine cynomolgus monkeys (Macaca fascicularis) were immunized with seven intramuscular injections of gp130-KLH, equivalent to a total of about 1.1 mg of purified gp130 per animal. The first three applications were formulated in Freund's incomplete adjuvant. Because of the effects of Freund's incomplete adjuvant, aluminum hydroxide was used for the four subsequent immunizations. Each of the nine vaccinated animals along with six controls were challenged with 10 monkey infectious doses (MID₅₀) of live HIV-2ben. At the time of challenge, the vaccinees had developed anti-gp130 titers ranging from 1 to 1.5 x 10⁵. Four animals exhibited neutralizing antibodies. After iv challenge with 10 MID₅₀ of HIV-2ben the nine vaccinees showed neither a secondary immune response nor a transient viremia. However, in four of the nine immunized animals proviral sequences were sporadically detected by polymerase chain reaction (PCR) and one of these four animals developed cytotoxic T lymphocytes. All six control animals developed a primary antibody response to HIV-2ben and became PCR positive. Four animals showed cytotoxic T cell activity and two developed a transient viremia. The five vaccinees with no sign of virus infection were reimmunized once and challenged with 10 MID₅₀ of the heterologous virus HIV-2SBL-6999. Four weeks later all animals were PCR positive. A naive control animal and four of the vaccinees showed primary or secondary antibody responses and transient viremia. One of the revaccinated animals did not become viremic, and viral antibodies did not increase.