May 1999: Grants Target Vaccine Research and Immune Reconstitution

In May 1999, the American Foundation for AIDS Research announced new grant awards totaling $1,703,031 to 19 research teams working in the areas of AIDS vaccine development and immune reconstitution. As always, the proposals selected underwent a rigorous peer-review process by members of amfAR’s distinguished Scientific Advisory Committee, a team of renowned scientists who volunteer their time and expertise to evaluate the scientific merit and relevance of the applications. The awards consisted of nine grants in the vaccine research, totaling $953,031, and ten grants for studies in immune reconstitution, totaling $750,000.

One of amfAR’s foremost goals is the development of a safe, effective, inexpensive, and easily accessible AIDS vaccine. To this end, in 1997, the Foundation launched a targeted initiative to fund research on innovative approaches to stimulating the immune responses necessary to stop HIV infection from occurring or to prevent HIV infection from progressing. In October 1999, the Foundation solicited a second round of proposals on new approaches for enhancing qualitative and quantitative cellular or antibody immune responses to HIV.

The nine researchers who will receive Foundation funding for their work in vaccine research are:

• Adolfo Garcia-Sastre, Ph.D., Mount Sinai School of Medicine
• Luis D. Giavedoni, Ph.D., Southwest Foundation for Biomedical Research
• Janis V. Giorgi, Ph.D., UCLA School of Medicine
• Ian Martin Jones, Ph.D., NERC Institute of Virology and Environmental Medicine
• Hilary Koprowski, M.D., Thomas Jefferson University
• Gunter Kraus, Ph.D., University of Miami
• Dan R. Littman, M.D., Ph.D., New York University Medical Center
• Jack H. Nunberg, Ph.D., University of Montana
• Martin J. Vincent, Ph.D., Emory University.

Drs. Koprowski, Littman, and Nunberg are receiving grant renewals.

Their investigations will include determining whether a DNA vaccine that causes the expression of HIV antigens along with molecules that stimulate the immune system can prevent disease progression in primates; using improved variants of the HIV surface envelope protein to generate a broader immune response; building on the discovery of “fusion competent” whole cell immunogens to develop a clinically acceptable recombinant vaccine; investigating the relation between HIV antigen expression level and antibody response; using plant viruses to develop a system for the production of an inexpensive, safe, and effective HIV vaccine; and engineering new strains of mice that can be used to test AIDS vaccine candidates for their ability to elicit effective antiviral responses.

The Foundation’s targeted grant initiative in vaccine research is coupled with a commitment to research in immune reconstitution. The new highly active antiretroviral therapies (HAART), or antiretroviral drugs given in combination, have had a significant, positive impact on HIV disease progression and mortality, at least in the short term. But there are disturbing preliminary data that subsets of new, naïve T-cells, which are needed to restore functional immunity against HIV, may not return to normal levels with HAART alone. In October 1998, amfAR solicited proposals for research to achieve immune reconstitution, including the exploration of new approaches to encourage the generation of new T cells, enhance T lymphocyte diversity and function, and expand the number and function of memory and naïve T cells, as well as studies of innovative therapies to control HIV replication while restoring or maintaining immune function.

The ten researchers awarded amfAR funding for projects in immune reconstitution are:

• Rita B. Effros, Ph.D., University of California, Los Angeles
• Georges Herbein, M.D., Ph.D., University of Texas Medical Branch at Galveston
• Nigel Killeen, Ph.D., University of California, San Francisco; Alan L. Landay, Ph.D., Rush Presbyterian St. Luke’s Medical Center
• Bruce K. Patterson, M.D., Northwestern University Medical School
• Mark C. Poznansky, M.D., Ph.D., Massachusetts General Hospital
• Carlos Subauste, M.D., University of Cincinnati
• Giorgio Trinchieri, M.D., The Wistar Institute
• Kenneth I. Weinberg, M.D., Childrens Hospital Los Angeles
• Jerome A. Zack, Ph.D., Regents of the University of California.

Drs. Weinberg and Zack are receiving grant renewals.

Their projects will include using a novel gene therapy approach to increase the proliferative potential of protective immune cells; exploring whether lack of immune reconstitution is due to altered stem cell function or thymic function; examining the basic mechanisms that control the number of T helper cells; studying how to prevent the destruction of thymus T cells by HIV infection in children; using organ culture systems to improve the production of T lymphocytes in the adult human thymus; identifying biomarkers that distinguish new T cells from memory cells in order to better evaluate immune reconstitution; and exploring whether stimulated production of cytokines, such as interferon-gamma and interleukin-12, can help restore immune function.

amfAR’s vaccine research initiative is principally supported by grants from Concerned Parents for AIDS Research (CPFA), a Foundation affiliate that brings parents together in the struggle against AIDS; Gift for Life, a gift industry group that supports AIDS research and education; and Young Executive Support (Y.E.S.), a volunteer committee of New York-area professionals dedicated to raising AIDS awareness and mobilizing support for AIDS research. Other supporters include The Frances L. & Edwin L. Cummings Memorial Fund and the Metropolitan Life Foundation. The Foundation’s investment in immune reconstitution research is underwritten by Gift for Life, Y.E.S., the William Randolph Heartst Foundation, and Club Cabaret in Kansas City, Missouri. Significant support for amfAR’s basic research programs has also been provided by the Vincent P. Belotsky, Jr. Foundation, The Canno Foundation, the F.M. Kirby Foundation, The Ambrose Monell Foundation, and The Xerox Foundation.