Abstract:
Simian immunodeficiency virus (SIV) infection of macaques is an ideal model for evaluating candidate HIV vaccines since SIV induces an immunodeficiency syndrome similar to human AIDS. Thus, potential vaccines can be evaluated for their ability not only to prevent infection but also for efficacy in preventing or delaying the onset of AIDS. However, many vaccines are only evaluated for their ability to prevent infection and therefore, animals are not evaluated long enough to determine whether immunization affects subsequent disease. The purpose of the present study was to use the SIV model to determine whether prior vaccination with a killed whole virus immunogen would alter the course of disease. Therefore, we studied a group of macaques immunized with whole inactivated SIV (WI-SIV) that became infected following a heterologous, cell-associated SIV challenge. Five immunized and six naive pig-tailed macaques were studied. The control group consisted of two animals challenged in parallel with the immunized group and four animals challenged with the same dose of virus as part of an infectivity titration of the challenge pool. All animals became infected regardless of immunization and an initial decline in absolute circulating CD4 lymphocytes and peripheral lymphadenopathy was observed in both groups. However, one vaccinee was only transiently viremic and has remained immunologically and clinically normal throughout the study. Although virus could be isolated from the peripheral blood mononuclear cells (PBMC) of all animals, no virus was detected in the plasma of immunized animals even during a period corresponding to peak viremia in the naive group. Animals were monitored for clinical evidence of AIDS and sacrificed if their clinical condition deteriorated or life-threatening signs were observed. All the naive animals were sacrificed by 18 months due to a variety of opportunistic infections. In contrast, three of the vaccinees remain alive. Therefore, the mean survival of vaccinees was significantly lower (527 days) than that of control macaques (257 days). These long-term survivors maintained high levels of SIV-specific antibodies and normal numbers of CD8 lymphocytes in the peripheral blood. These data suggest that prior vaccination with whole inactivated SIV induces significant protection from immunodeficiency following subsequent SIV challenge.
Keywords: Animal Antibodies, Viral/*BLOOD Antigens, CD4/BLOOD Antigens, CD8/BLOOD Lymphocytes/MICROBIOLOGY Macaca nemestrina Simian Acquired Immunodeficiency Syndrome/*IMMUNOLOGY/*PREVENTION & CONTROL SIV/*IMMUNOLOGY T-Lymphocyte Subsets/IMMUNOLOGY Vaccines, Inactivated/*THERAPEUTIC USE Viral Vaccines/*THERAPEUTIC USE ABSTRACT 940730
M9470914
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