AEGiS-11IAC: Chemically inactivated whole HIV vaccine induces cellular responses in mice.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

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Chemically inactivated whole HIV vaccine induces cellular responses in mice.

Int Conf AIDS 1996 Jul 7-12; 11:4 (abstract no. Mo.A.100)
Addawe MD, Fabrizzi F, Dourmashkin R, Wilson S, Oxford JS; Department of Academic Virology and Retroscreen Ltd., London Hospital Medical College, London, UK.

OBJECTIVES: To investigate the immune response in mice to an experimental whole virus chemically inactivated HIV-1 vaccine. Methods and

RESULTS: Groups of female mice (Balb/c) were immunised with two doses (10 micrograms and 1 microgram) of a whole HIV MN virus grown in C8166 cells. The vaccine production procedure involves using a multiple step inactivation of HIV-1 virus containing supernatant with two independent treatments of 0.2% Beta-propiolactone (BPL), concentrated and purified by ultra-filtration and ultra-centrifugation with 20%-60% sucrose density gradient respectively. Virus purification was confirmed by Western Blot and Electron microscopy. Binaryethylenimmne (BEI;10mM) was then used in additional inactivation of the virus followed by stabilisation with 0.05% Formaldehyde. Animals were boosted with vaccine at three week intervals and after three boosts sera and splenocytes were removed. Splenocytes were separated into CD4+ and CD8+ T-cell subpopulations by panning with specific antibodies and re stimulated in vitro for 6 days with either gp120,or V3-loop peptides derived from MN virus. Major histocompatibility (MHC) class I and II restricted HIV-1 env-specific CTL activity was determined using 51Cr-labelled murine P815 (H-2d) and A.20 (H-2IA) cell as targets pulsed with V3-loop peptide or gp120. Sera were assayed for reactivity to V3-loop peptide and rgp120 using ELISA and for virus neutralisation using syncytium reduction in C8166 cells. Splenocytes taken from mice immunised with this vaccine demonstrated HIV-1 env specific cytotoxic activity but no CTL activity was detected in control mice. High antibody titres to whole virus and to recombinant gp120 were also detected in the sera of animals immunised with the lowest dose of vaccine (1/ microgram). These antibodies also cross-neutralised MN, IIIB, and RF viruses.

CONCLUSIONS: The chemically inactivated HIV vaccine was found to be highly immunogenic in mice, inducing both Neutralising antibody and HIV-1 env-specific cytotoxic T-lymphocytes. Previous studies (Race E, et al. Vaccine 1995 vol. 13 number 16. ppp. 1567-1575) have established the inactivation kinetics using the four step methodology and in excess of 20 log10 TCID50 of virus is destroyed. The vaccine therefore fulfills the initial basic requirements of safety and ability to induce a B and T cell immune response, at least in a laboratory model.

Keywords: AEGIS, AIDS Vaccines, HIV-1, T-Lymphocytes, Cytotoxic, Giant Cells, Antigens, CD8, Peptides, Mice, Inbred BALB C, Antigens, CD4, Mice, Animal, Female, In Vitro, ICA11KWDaegis,aidsvaccines,hiv-1,t-lymphocytes,cytotoxic,giantcells,antigens,cd8,peptides,mice,inbredbalbc,antigens,cd4,mice,animal,female,invitro,ica11

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MoA100

Copyright © 1996 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.