HIV-1 Vaccine Development: studies in Macaque models

Abstract

Since its discovery about 15 years ago, human immunodeficiency virus type 1 (HtV-1) continues·to spread at an alarming rate. It is estimated that by the year 2000 between 30 and 40 million people will be infected with this virus worldwide'. Of these, about 90 % live in developing countries. To date, more than six million people have already developed to the fatal acquired immunodeficiency syndrome (AIDS). Despite numerous research efforts no vaccination or generally accessible therapeutic approach has become available yet. In 1981, the first case of AIDS was recognized'. Epidemiologic studies implicated an infectious agent and in 1983, the isolation of a previously unknown human retrovirus called lymphadenopathy-associated virus (LA V) from an AIDS patient was reported by Barre-Sinoussi et al.'. In 1984, Gallo et aI' and Levy et a/s also reported the isolation of retroviruses from AIDS patients which they called human T-Iymphotropic virus type III (HTLV-III) and AIDS-associated retrovirus (ARV), respectively. Soon thereafter, these retroviruses were recognized as members of the Lentivirinae, a subfamily of the Retroviridae, and were indeed identified as the etiological agents of AIDS. In 1986, these retroviruses were named human immunodeficiency virus (HIV). Today, two types of HIV are recognized, HIV-1 and HIV-2. Of these, HIV-1 is the primary etiologic agent of the current AIDS pandemic. The search for an HIV-1 counterpart in other primate species led to the identification of several simian immunodeficiency viruses (SIV), which may cause AIDS like syndromes in monkeys'. Currently, macaque lentivirus infections are considered the most appropriate animal models to study HIV pathogenesis and possible intervention strategies. In the following section, a concise overview is given of the biology of primate lentiviruses, including the host immune response and correlates of immune-mediated protection. Aspects important for vaccine development are highlighted