Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
PR Newswire; Monday September 14, 1998
In July 1998 I was among the over 13,000 participants who attended the 12th International AIDS Conference, in Geneva, Switzerland. I would like to share with you some of the highlights of the meeting as they relate to the work on the development of an AIDS vaccine at CEL-SCI.
The meeting opened with a plenary lecture by Dr. Peter Piot, Director, UNAIDS in Geneva. He painted a grim picture for HIV infection and AIDS in the developing countries, especially in Africa and Asia. He indicated that approximately 80% of the HIV-infected people in the world currently live in Africa and Asia, while 90% of new infections are occurring in these regions. In addition, 3 million new infections were reported in South Africa and 4 million in India in the last year alone. Not surprisingly, the infection rate is the highest in young adults (16-29 yr.), reaching as high as 35-40% in some cities in Africa. By the year 2000, there will be an estimated 40 million people infected with the virus worldwide. Unfortunately, these regions lack the funds to provide the medical care and to purchase the expensive medicines necessary to treat these infected people. The cost of treating an HIV- infected person in the United States for one year is about $12-15,000. Resources to provide education in AIDS prevention are also lacking.
The general consensus from the meeting was that the only hope to curb the spread of AIDS in the developing countries is to develop a preventive vaccine. CEL-SCI has made the development of an AIDS vaccine a primary goal. We at CEL-SCI are excited at the prospect of developing a product that may prevent millions of people from contracting AIDS. I will try to address some of the issues in Q&A format as they relate to CEL-SCI's AIDS development program.
Q. Dr. Sarin, you are the scientific head of the CEL-SCI team charged with the exciting assignment of moving the AIDS vaccine forward. What are your qualifications for the job and why did you take on such a challenging task?
A. Everyone loves a challenge and I am no exception. AIDS is a global epidemic, which is especially acute in the developing countries in Africa and Asia. By the year 2000, there will be approximately 40 million HIV-infected people worldwide. Without a vaccine there will be no end to this epidemic and whole generations of young adults will be wiped out. Development of an AIDS vaccine is a top priority of not only CEL-SCI, but also of President Clinton and Dr. Peter Piot, Director of UNAIDS. It will be extremely satisfying to see a CEL-SCI vaccine helping control the spread of AIDS worldwide. I have been involved in AIDS research from the early onset of the epidemic around 1983 and I feel that I have a special obligation to see that something concrete is urgently done to control the epidemic, especially in the developing countries. I have published over 200 papers relating to cancer, AIDS and retroviruses and have been involved in studies on HIV pathogenesis, drug and vaccine development for the last 15 years. I have participated in studies on CEL-SCI's AIDS vaccine approach from the very beginning. Based on my training and experience at Harvard University, Merck Sharp & Dohme, National Institutes of Health and George Washington University, I consider myself very well qualified to complete the task of developing an effective AIDS vaccine. My main reason for taking up this task at CEL-SCI was the opportunity to move the research and development of a vaccine at a much faster rate than is possible at academic or government institutions, so as to help prevent catastrophic losses of large populations of young adults to AIDS worldwide.
Q. What does HGP-30W stand for?
A. It means HIV Gag Protein 30 Worldwide. Gag is the scientific term for core of the virus. The original formulation of the vaccine utilized a peptide containing 30 amino acids. Worldwide highlights our goal of developing a vaccine that would work in different parts of the world.
HGP-30W is a synthetic peptide vaccine modeled after a part of HIV-1 p17 protein. HIV-1 p17 is a core protein of the virus that is less variable among different HIV strains and subtypes found around the world than the competing HIV-1 envelope glycoproteins (gp120/gp160). In addition, the HGP-30W vaccine is designed to induce cellular immune responses that can kill and remove virus infected cells.
Q. How does CEL-SCI's AIDS vaccine differ from others?
A. Two general protein-based approaches are being pursued. One approach uses the envelope (outside) of the virus to generate antibodies that may be able to neutralize the free virus circulating in blood. The second approach uses the core of the virus to induce cell-mediated immune responses which can kill and remove virus infected cells that act as reservoirs for new virus particles. CEL-SCI uses the second approach.
Q. Why do you think CEL-SCI's approach is better than other approaches?
A. CEL-SCI focuses on the core of the virus which is less variable among different strains and subtypes than the envelope of the virus. The envelope changes rapidly due to genetic mutations. Hence, an envelope-based vaccine made against one HIV subtype may not recognize other virus subtypes, whereas a core-based vaccine is more likely to be able to recognize different virus subtypes present around the globe.
Q. Are there differences in HIV found in North America and other parts of the world?
A. Yes. Several HIV subtypes have been identified from HIV-infected individuals in different parts of the world. Subtype B is prevalent in North America, South America and Western Europe. Major HIV subtypes in Africa are A, C and D. India has subtype C and subtype E is prevalent in Thailand.
Q. Can CEL-SCI's vaccine work against different HIV subtypes found around the world?
A. CEL-SCI's vaccine is designed to work against major HIV subtypes (A, B, C, D & E) found in Africa, Asia, North and South America and Europe. In contrast, the envelope-based vaccines being tested are based on the B subtype prevalent in North America and Europe and hence, may not be very useful in the developing countries.
Q. Can CEL-SCI's vaccine cause AIDS infection in individuals who receive the vaccine?
A. Absolutely not! CEL-SCI's HIV vaccine (HGP-30W) is a peptide-based vaccine made by joining several amino acids (somewhat akin to LEGO(R) building blocks). It does not contain infectious "live" virus, killed virus or attenuated virus (a virus from which one or more viral genes have been deleted) and hence it cannot cause AIDS infection.
Q. Do you have evidence of protection against virus infection with your vaccine?
A. Yes. Five uninfected human volunteers who had received the HGP-30 vaccine and three uninfected non-vaccinated volunteers donated blood for this test. Their blood cells were injected into SCID mice, which are mice that are genetically engineered not to reject human cells. The mice, with human blood in them, were then injected with live AIDS virus.
RESULT: 78% of the mice that received blood from HGP-30 vaccinated volunteers were protected. By comparison, only 13% of mice that received blood from non-vaccinated volunteers were protected.
Q. Have you tested your vaccine in humans?
A. Yes. CEL-SCI's HIV vaccine has been tested in 38 HIV-negative individuals in Phase I clinical studies carried out in the U.K. and U.S. and 24 HIV-infected patients in the U.S. In these clinical studies, the vaccine has been shown to be safe and well-tolerated. In addition, it induced the desired immune responses in HIV negative people that show evidence of recognition of different HIV subtypes and of protection against virus infection.
Q. What human studies are you currently doing with your vaccine?
A. CEL-SCI's AIDS vaccine (HGP-30W) is currently in a Phase II clinical trial in 30 HIV-negative volunteers in the Netherlands. This clinical trial will provide further information on the safety of the vaccine and immune responses generated by the vaccine. In addition, this clinical study will identify the most suitable vaccine dose for future clinical trials.
Q. Where do you intend to perform studies to prove that the vaccine works?
A. In Africa! Since the HIV infection rate is the highest in Africa, it will take less time (3-5 years) to obtain data to prove that the vaccine works than if the studies were carried out in the U.S. or Europe where the infection rates are much lower. In addition, we would need significantly fewer volunteers to carry out the vaccine efficacy study in Africa than in the U.S. or Europe. Also, the need is greatest in Africa.
Q. What are the prospects of CEL-SCI developing a successful AIDS vaccine?
A. We believe the prospects are good. We are excited to be developing a vaccine that may save millions of people worldwide, who are at risk of becoming HIV-infected. Our strategy is based on the development of a vaccine that can induce protective immunity against the major HIV subtypes prevalent in Africa, Asia, North and South America and Europe.
Q. What is the competitive position of the HGP-30 AIDS vaccine? I recently read about another company going into a large clinical trial with an AIDS vaccine.
A. Newsweek magazine recently listed CEL-SCI as one of the three leading AIDS vaccine companies with products currently in advanced clinical trials. The other vaccine companies listed were VaxGen and Pasteur Merieux/Connaught (the subsidiary of Rhone Poulenc). The major focus of these two companies is the development of a vaccine targeted to the HIV-1 B subtype prevalent in North America and Europe. In contrast, CEL-SCI's vaccine is targeted towards major HIV-1 subtypes prevalent around the world. In addition, CEL-SCI believes that generating an effective cellular immune response, rather than an antibody response as produced by VaxGen's vaccine candidate, will be the key factor in controlling the infection by destroying the virus-infected cells that act as reservoirs for new virus particles. As mentioned previously, CEL- SCI's HGP-30W vaccine is currently in a Phase II trial in the Netherlands.
Q. Do you have any closing thoughts?
A. We are among a very small number of companies making progress against one of the biggest killers of our time. There are still many things that we do not understand in dealing with the AIDS virus. Up to this point my colleagues at CEL-SCI and I believe the data have supported our vaccine approach and will continue to do so. We face many challenges in moving the vaccine development forward. Unfortunately, one of them is international politics. In November of 1997, we were just a few days from initiating a Phase II human study in Zambia, Africa, when we were told to stop by the Health Ministry. Even though the required committees approved our study, we have not yet received the approval to proceed. Who would have imagined that our vaccine, designed to help Africans, already tested in humans in Europe and the U.S., and cleared by the African scientific committees, would not get the political approval? It should be noted that infection rates in young adults in urban areas of Zambia have been reported to be as high as 30%. My colleagues and I will continue to do all we can to obtain the political and scientific support necessary to advance the development of an AIDS vaccine.
Q. For those of us who want to learn some of the underlying science regarding the development of AIDS vaccines, where do you suggest we go?
A. I suggest that you start with the "Backgrounder" that CEL-SCI has assembled on HGP-30 and AIDS vaccines in general. It is available from our web site www.cel-sci.com or by calling CEL-SCI at (703) 506-9460. In addition, I have listed for you at the end of this letter some additional references on CEL-SCI's vaccine (1-5) and general discussions on AIDS vaccine development (6-11). Thank you for your interest. I hope that this information will be useful for you. We hope that you will continue to support our efforts to develop an AIDS vaccine.
Selected references
1. Gazzard et al Safety and immunogenicity of HGP-30. Evaluation of a synthetic HIV-1 p17 vaccine in healthy seronegative volunteers. Vaccine Res. 1:129-135 (1992).
2. Sarin et al. Cytotoxic and humoral immune responses to HIV-1 p17 synthetic peptide HGP-30 in human volunteers. Vaccine Res. 3:49-57 (1994).
3. Sarin et al. HIV-1 p17 synthetic peptide vaccine HGP-30: Induction of immune response in human subjects and preliminary evidence of protection against HIV challenge in SCID mice. Cellular & Mol. Biol. 41: 401-407 (1995).
4. Zimmerman et al. Cross-clade peptide recognition by antisera to HGP- 30, a 30-amino acid synthetic peptide antigen from HIV type 1 p17. AIDS Res. Hum. Retroviruses, 14: 741-749 (1998).
5. Sarin et al. HGP-30W vaccine induces cross clade recognition (A,B, C,D,E) and amplification of cellular immune responses (TH-1) with different adjuvants in a prime-boost protocol. In, 12th World AIDS Conference, Geneva, Switzerland, 1998, Basic Science vol.1, pp265-269, Monduzzi Editore S.p.A., Bologna, Italy.
6. Esparza et al. HIV preventive vaccines. Progress to date. Drugs 50: 792-804 (1995).
7. Dolin et al. Human studies on the development of human immunodeficiency virus vaccines. J. Infect. Dis. 172: 1175-1183 (1995).
8. Bolognesi. Overview of HIV vaccine development. Antibiot. Chemother. 48: 63-77 (1996).
9. Haynes et al. Towards an understanding of protective immunity to HIV infection. Science, 271: 324-328 (1996).
10. Mascola et al. Immunization with envelope subunit vaccine products elicits neutralizing antibodies against laboratory adapted but not primary isolates of human immunodeficiency virus type 1. J. Infect. Dis. 73: 340-348 (1996).
11. Connor et al. Immunological and virological analyses of persons infected with human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines. J.Virol 78: 1552-1576 (1998).
Additional materials available on request or available at: http://www.cel-sci.com
"CEL-SCI press releases are available through Company News On-Call by fax, (800) 758-5804, Ext. 445563 or at http://www.cel-sci.com on the Internet."
When used in this report, the words "intend," "believes," "anticipated" and "expects" and similar expressions are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties which could cause actual results to differ materially from those projected. Factors that could cause or contribute to such differences include, an inability to duplicate the clinic results demonstrated in preclinical studies, timely development of any potential products that can be shown to be safe and effective, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products and the risk factors set forth from time to time in CEL-SCI Corporation's SEC filings, including but not limited to its report on Form 10-K for the year ended September 30, 1997. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.
SOURCE: CEL-SCI Corporation
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