Third International Congress Drug Therapy in HIV Infection 3-7 November 1996 Glasgow, UK

HIV VACCINES - TOWARDS PHASE III

Jonathan Weber
Dept of GU Medicine & Communicable Diseases, Jefferiss Research Trust Laboratories, Imperial School of Medicine at St Mary's, Praed Street, London WC2 1 NY

Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. 3.2
AIDS 1996, Vol. 10 (Suppl. 2);S2

Research for an effective vaccine to prevent HIV infection continues to be a priority, although mostly by government funded scientists. Ten years of endeavour has led to tangible achievements, particularly around animal models for vaccine development and the genomic characterisation of HIV-1 diversity. However, there is considerable confusion regarding the likely efficacy of any of the potential vaccines in clinical trials and many believe that research is stalled.

The animal systems developed for HIV vaccine research include the FIV/cat, the SIV/macaque and the HIV/chimp models. Of these, the SIV/macaque is the most developed. Protection against SIV challenge has not been achieved with inactivated SIV and only intermittently with r.gpy molecules. However, live attenuated SIV protects potently against challenge, although the mediator of protection is not clearly defined Thus the SIV/macaque model would suggest that a live viral vaccine is required but, given the safety concerns of a replicating HIV genome, however attenuated, it is difficult to extrapolate from the animal model to the human situation. In the FIV/cat model, inactivated virus but not r.env protects, however, in the chimp owl protects, but not fixed, inactivated virus.

Human trials at Phase I and II have, therefore, taken place against a background of inadequate knowledge on which immune parameters should be used for selection. Neutralising antibodies which appear to be relevant in the chimp/HIV model are not found to be significant in the SIV/macaque model. Cytotoxic T. lymphocytes are thought to be important in the macaque model and in exposed, but uninfected, humans. However, some of this protection might even be chemokine related;. and not necessarily antigen specific.

The r.env gpl20/gpl60 molecules are safe and immunogenic, although the neutralising antibodies they induce do not affect primary (field) isolates of HIV-1. The viral vectors, such as avipox, with an r.env boost, do include Nabs as well as CTL, and are in progress in Phase II trials.

A Phase III trial now hangs in the balance. On one hand, safe, immunogenic vaccines of questionable efficacy; on the other hand, a large trial with no guarantee of a scientifically useful result. In the past, vaccine development has been run empirically if not immunologically. The field will probably progress faster if the same precepts continue.

Presenting author: Jonathan Weber

1996-11-03
3.2

Originally published in AIDS Volume 10, Supplement 2 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

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