Researchers progress toward AIDS vaccine

March 13, 2009

NEW BRUNSWICK, N.J. - Rutgers AIDS researchers Gail Ferstandig Arnold and Eddy Arnold may have turned a corner in their search for a HIV vaccine. In a paper just published in the Journal of Virology, the husband and wife duo and their colleagues report on their research progress.

With the support of the National Institutes of Health, the Arnolds and their team have been able to take a piece of HIV that is involved with helping the virus enter cells, put it on the surface of a common cold virus, and then immunize animals with it. They found that the animals made antibodies that can stop an unusually diverse set of HIV isolates or varieties.

Some researchers have previously been able to elicit effective antibodies, but usually only against a very limited number of HIV types. With HIV's known propensity to mutate, antibodies developed against one local strain may not recognize and combat mutant varieties elsewhere. These geographic varieties with different mutations constitute one of the great challenges to finding a broad spectrum vaccine capable of protecting against the vast array of HIV varieties.

The approach taken by the Arnolds and their colleagues has been to identify a part of the AIDS virus that is crucial to its viability - something the virus needs in order to complete its life cycle - and then target this Achilles heel.

"The part that we targeted plays a role in the ability of HIV to enter cells, and is common to most HIV varieties," Gail Ferstandig Arnold said. "That is a mechanism that would not be easy for the virus to reinvent on the fly, so it turns out to be a really helpful target."

The Arnolds are both members of the Center for Advanced Biotechnology and Medicine, a joint center of Rutgers, The State University of New Jersey, and the University of Medicine and Dentistry of New Jersey. Also, Gail Ferstandig Arnold is a research professor and Eddy Arnold is a professor, both in Rutgers' Department of Chemistry and Chemical Biology.

While most vaccines are actually made from the pathogen itself, employing weakened or inactivated organisms to stimulate antibody production, HIV is just too dangerous to use as the basis for a vaccine vehicle. What the Arnolds have done is to use the relatively innocuous cold-causing rhinovirus and attach the target portion of the HIV. This must be done in a way that maintains the HIV part's shape so that when the immune system sees it, it will actually mount an immune response as it would to the real HIV.

"The idea is to trick the immune system into thinking it is acting upon HIV before the virus shows actually shows up on the scene," said Eddy Arnold.

To actually accomplish this is a big problem in engineering. The goal was to take a small piece of the HIV out of its native context, put it in a completely different system (rhinovirus), and have it look the same and act the same. Eddy Arnold likens this to taking the Rocky Mountains, putting them on India and having them look exactly right.

Using recombinant engineering, the research team developed a method to systematically test millions of varied presentations of the HIV segment with the rhinovirus. They tried millions of different variations on how to graft (or splice) one onto the other, creating what are called combinatorial libraries.

"It's like the lottery," Eddy Arnold commented. "The more tickets you buy the better chance you have of winning."

"The really exciting part is that we were able to find viruses that could elicit antibodies against a huge variety of isolates of HIV. That is an immense step and a very important step," said Gail Ferstandig Arnold.

"However, we need to be careful to not overstate things because the quantity of response is not huge, but it is significant," added Eddy Arnold. "This is actually the first demonstration of this particular Achilles heel being presented in way to generate a relevant immune response. It is probably not potent enough by itself to be the vaccine or a vaccine, but it is a proof of principle that what we are trying to do is a very sound idea."

Rutgers University

---

---

	AIDS Vaccine Research by WonG-Staal/Gall (Author) This reference describes the latest advances in the development and design of an HIV preventive vaccine-detailing the pathogenesis and genetic variability of HIV infection for the construction of molecular and therapeutic strategies to reduce the progression and transmission of AIDS. With contributions by universally recognized authorities in the field, AIDS Vaccine Research discusses § major obstacles in the identification of a preventive vaccine § the role of innate immunity in management of HIV infection § the impact of highly active antiretroviral therapy (HAART) on AIDS research § the creation of an effective mucosal DNA vaccine § the effect of the AIDS epidemic on developing countries Offering nearly 2000 contemporary references to facilitate further study, AIDS Vaccine...
	Shots in the Dark: The Wayward Search for an AIDS Vaccine by Jon Cohen (Author) "[A]n important book not only for the now but for the future of this epidemic and those to come."—Dr. Robert GalloWhen scientists proved in 1984 that HIV causes AIDS, a vaccine race spun into action. But the sprint to develop an AIDS vaccine now more closely resembles a crawl. Jon Cohen elucidates the forces that have hindered the search: unforeseen scientific obstacles, clashing personalities, the uncertain marketplace, haphazard political organization, and serious ethical dilemmas. Beyond a powerful critique, Cohen also offers specific recommendations for accelerating the effort. 6 pages of b/w photographs.
	Big Shot: Passion, Politics, and the Struggle for an AIDS Vaccine by Patricia Thomas (Author) A veteran journalist dramatizes the controversial search for an AIDS vaccine-the players, the politics, the money-in a vivid, suspenseful story that reveals how science is done, and not done, in America today. . When the human immunodeficiency virus was identified in 1984, the competition to create an AIDS vaccine was fierce. Now Patricia Thomas brings the contenders to life in a fast-paced, dramatic narrative: Two biologists rescue precious virus cultures from destruction by a military biohazard team. Other researchers drive hundreds of miles during a heat wave to work in a safe containment lab. And a heroic figure from Randy Shilts's And The Band Played On just might win the vaccine marathon. Thomas shows how the scientists' youthful optimism is honed into gritty determination as they...
	HIV And Molecular Immunity: Prospects for the AIDS Vaccine by Omar Bagasra (Author) How old is the AIDS virus (HIV-1) and where did it come from? Is it the result of a recombinant event in simian immunodeficiency viruses (SIVs)? Why do SIVs naturally occur in a variety of nonhuman African primates without inducing AIDS in their natural hosts? HIV-1 has devastated human society, although chimpanzees carry an SIV that is genetically almost identical to HIV-1 but causes no known illness in these great apes. How are Chimpanzees immune to HIV-1? Can humans acquire this immunity? Why do most newborns infected with HIV-1 in utero or during birth become long-term non-progressors while 20% rapidly develop AIDS and die in less than a year? Why are some adults asymptomatic for over 10 years after infection? Dr. Omar Bagasra, an eminent molecular biologist, immunologist, and...
	AIDS Vaccine Development: Challenges and Opportunities by Wayne Koff (Editor), Patricia Kahn (Editor), Ian D. Gust (Editor) The HIV/AIDS pandemic is the most devastating global public health crisis since the great plagues of the Middle Ages, with more than 14,000 new HIV infections and 8,000 deaths due to AIDS every day. Although successful vaccines have been developed for most common childhood diseases, the development of a vaccine against the AIDS virus is a much greater challenge. More than 20 years after the discovery of the virus, the goal of a licensed and globally accessible vaccine is still several years away. AIDS Vaccine Development reviews the scientific challenges that have impeded the search for an effective AIDS vaccine and discusses current novel research that is accelerating progress. In a series of mini-reviews by the world's leading experts in AIDS vaccine research, the book provides...
	Adoption of Health Technologies in India: Implications for the AIDS Vaccine (Studies in Economic and Social Development) by Indrani Gupta (Author), Mayur Trivedi (Author), Subodh Kandamuthan (Author) The first of its kind, this book examines the adoption of four health technologies in India-Hepatitis B, No Scalpel Vasectomy, Voluntary Counseling and Testing, and Antiretroviral Treatment. Using a set of parameters, the authors not only bring to light the various dimensions, strengths, and weaknesses of adoption of health technologies in India, but also how and where more attention needs to be paid with regard to the adoption of the AIDS vaccine.
	Immunology: From Pasteur to the Search for an AIDS Vaccine (Venture Books) by Martin J. Gutnik (Author) A history of immunology from the discovery of microorganisms with the invention of the microscope to the development of vaccines for treating diseases.
	Vaccines 91: Modern Approaches to New Vaccines Including Prevention of AIDS by Robert M. Chanock (Author), H. Ginsberg (Author), F. Brown (Author), R. Lerner (Editor)
	Expanding Access to Investigational Therapies for HIV Infection and AIDS by Roundtable for the Development of Drugs and Vaccines Against AIDS (Author), Institute of Medicine (Author) The call for a "parallel track" for AIDS drug development-a proposal that would allow the early distribution of AIDS drugs to large numbers of patients in parallel with the conventional clinical trials that assess the drugs' safety and efficacy-has sparked controversy within the scientific community. Questions have arisen about the risks to patients of such a plan, about its potential effect on the successful completion of standard controlled trials, and about whether the parallel track will generate useful data. Larger questions have also been raised about whether the parallel track heralds fundamental changes in the philosophy underlying drug regulation in the United States, about the costs and financing of investigational therapies and associated medical costs, and about the role of...
	Vaccines 97 by Fred Brown (Author), Fred Brown (Editor), Dennis Burton (Editor), Peter Doherty (Editor), John Mekalanos (Editor), Erling Norrby (Editor) USDA, Plum Island Animal Disease Center. Proceedings from the meeting held September 9-13, 1996. Presentation of research on new approaches to infectious disease control. For the investigator. Softcover.