Scientific paper 35 – New scientific developments towards an AIDS vaccine: report on a workshop organized by EU programme EVA entitled Novel approaches to AIDS vaccine development held at the Institut Pasteur, Paris 16/17 November 1995

March 2, 2017 3:48 pm

New scientific developments towards an AIDS vaccine: report on a workshop organized by EU programme EVA entitled Novel approaches to AIDS vaccine development held at the Institut Pasteur, Paris 16-17 November 1995

Journal : Vaccine, 1996

Author: J S Oxford

Abstract text:

We are now into the second decade of the AIDS epidemic and the virus, ominously, is showing signs of evolving in new directions. To date, there have been two distinct epidemics. One occurs primarily in Europe and the USA and mainly affects men who have sex with men and intravenous (i.v.) drug users while the second centres on Asia and Africa where the virus has been spreading heterosexually. There is some evidence that distinct viruses with varying ability to grow in rectal or vaginal cells may be responsible. This is a worrying situation.

Antiviral chemotherapy is struggling with the problems of rapidly developing drug resistance, poor potency and poor bioavailability. which at best have kept patients alive and well a little longer. It will be very difficult, if not impossible, to cure an infection caused by a retrovirus which can integrate into chromosomal DNA.

So have the vaccineologists been more successful? Unfortunately the current vaccine strategy has, at least temporarily, been stalled due to the failure of vaccinated volunteers to produce antibodies that are capable of neutralizing field isolates. In addition, a number have, within 6 months of vaccination, contracted the disease, not from the vaccines (which are a non-infectious product of recombinant DNA technology). but rather from a failure of the vaccines to induce protective immunity. It should be noted, however, that the challenge to the vaccines may have been particularly severe as some of the vaccinees had multiple sexual partners over a 6 month period. With this setback in mind government agencies, particularly in the USA, are reconsidering their vaccine strategy. The NIH, for example, has now decided on a parallel track approach. All methods, including live attenuated or chemically inactivated whole virus, antigen subunits and live vectors produced (Received 28 May 1996; accepted 12 June 1996) by recombinant DNA technology, are being reevaluated.

To date, most viral vaccines registered for human use are composed of whole killed or live attenuated virus particles with the exception of the hepatitis recombinant subunit vaccines. However, the use of a live attenuated virus to control such a pleomorphic virus as HIV is unlikely to be acceptable at present. while safety fears remain over the use of whole killed virus. Despite this, a wide variety of studies using the SIV/macaque animal model have shown that such approaches can be successful. While the problems associated with whole virusbased vaccines continue to be addressed. other, often completely novel, approaches are being tried. These include; the use of recombinant viral vectors to deliver the antigen of choice directly to the host MHC Class I system, thus inducing cytotoxic lymphocyte (CTL) responses; recombinant subunit vaccines; chimaeric vaccines. consisting of a highly immunogenic carrier molecule which may or may not be based on a viral vector linked to the antigen of choice; synthetic peptides based on known immunodominant regions of the HIV virion and naked nucleic acid (NA) vaccines. All of these approaches have certain advantages and disadvantages but, providing the safety of such preparations can be established in Phase I and II trials, and given the unique nature of the host/parasite relationship pertaining in HIV infections, there is no reason why such novel approaches could not be efficacious in specific situations.

The need to develop an effective HIV vaccine is now more urgent than ever. There are CCI 20 million individuals infected with HIV and 4.5 million AIDS cases worldwide. The African epidemic has cost over $30 billion and the United Nations estimates that AIDS will reduce Africa’s overall labour force by as much as 25% by the year 2010. At the current rate, the impact on the worldwide economy is estimated to reach $514 billion by the year 2000 and, in a worst case scenario, will rob the world of 1.4% of its gross product. It is further recognized that identification of a safe and effective HIV vaccine will result in both financial and health benefits. For example, it costs ca $119000 to care for each HIV-infected individual over his/ her lifetime in the USA. The disease has already cost $75 billion, with $3 to $6 billion being spent on new infections each year. Costs to life and health insurance were nearly $1.6 billion in 1994: claims since 1984 total an estimated $9.4 billion. Furthermore, it has been estimated that AIDS will have cost the USA economy $81 to $107 billion by the year 2000.

It was in the context of this rather sombre scenario that a group of scientists met under the auspices of Programme EVA (European Vaccine against AIDS) at the Institut Pasteur in Paris to analyse scientific research in Europe which could provide a strong basis for further vaccine work. It should be clearly explained that it is not the objective of Programme EVA, despite its name, to produce or co-ordinate the production of an European AIDS vaccine but rather to produce and facilitate the critical laboratory reagents and infrastructure which are so necessary for a successful vaccine to emerge from the pharmaceutical companies.

The papers presented at this workshop encompass all of the “traditional” and “new wave” vaccine approaches listed above. Up until now, the antigen most widely available has been the envelope glycoprotein of HIV-l (gp130/160) from a B-clade isolate such as IIIB or the equivalent envelope glycoprotein from SIVmac. However, a number of recent Endings have drawn attention to the possibility that non-surface antigens may have a major role to play.

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