Looney D, McClure J, Kent S, Robertson M, Kraus G, Badel P, Steeles J, Doroteeva N, Schmidt A, Bartz C; National Conference on Human Retroviruses and Related Infections.
Program Abstr Second Natl Conf Hum Retrovir Relat Infect Natl Conf Hum Retrovir Relat Infect 2nd 1995 Wash DC. 1995 Jan 29-Feb 2; 91.
VA Medical Center San Diego, CA.
Objective: To investigate protection using live human retroviruses, we challenged previously inoculated with an avirulent, infectious, molecular HIV-2 clone (HIV-2 KR) with HIV-2(287), an HIV-2 isolate which produces rapid decline in CD4 lymphocyte numbers and immunodeficiency in Macacca nemestrina. Methods: HIV-2 KR was produced by transfection into Molt-4/Clone-8 cells. HIV-2(287) was obtained from the lymoh node of an HIV-2 EHO infected animal. The challenge pool was grown in M. nemestrina PBMC. Viral burden was assessed by quantitative viral culture, plasma antigen EIA, and internal standard DNA & RNA PCR. Antibody response was assessed using EIA, immunoblotting and radioimmunoprecipitation. Neutralization assays were performed on C8166 and HT 4-6C cells. Investigation of CTL activity and CTL precursor frequencies were performed using published methods. Results: HIV-2 KR was titrated on macaques using 10(1)-10(4) syncytia forming units (SFU) intravenously. Infection was detectable in all animals by nested PCR. By reisolation 1AID equalled approximately 100 SFU. A transient decline in CD4+ lymphocytes was seen in HIV-2 KR infected macaques. No neutralizing antibody, ADCC, pr CTL directed against homologous virus was detected in KR infected animals prior to challenge. Prior inoculation with HIV-2 KR failed to protect animals from infection, however, animals previously inoculated with 10(4) SFU of HIV-2 KR were protected from CD4 decline end disease following challenge with either 10(5) or 10(1) TCID(50) of HIV-2 (287). Protected animals displayed lower levels (1-2 logs) of proviral burden, plasma antigenemia, and viral RNA. These observations have prompted our current plans to explore the basis of virological and immunological basis of protection from disease produced by HIV-2 (287) challenge in HIV-2 KR exposed animals. Conclusions: Investigation of the kinetics and immunological basis of protection induced by infection with avirulent HIV-2 is underway, and may provide important information for the design and evaluation of HIV vaccines.
Publication Types:
Keywords:
- AIDS Vaccines
- Animals
- Antigens, CD4
- CD4-Positive T-Lymphocytes
- Clone Cells
- HIV-2
- Humans
- Macaca
- Macaca mulatta
- Macaca nemestrina
- Naphthalenes
- Polymerase Chain Reaction
- RNA, Viral
- T-Lymphocytes, Cytotoxic
- immunology
- protect
Other ID:
UI: 102213184
From Meeting Abstracts