Broadly-protective HIV1 Vaccine May Be Possible
New research conducted at the Uniformed Services University of the Health Sciences (USU) suggests that it may be possible to develop a vaccine that protects against the myriad strains of the HIV virus. HIV is extremely variable, so an effective vaccine may need to stimulate the body to produce cross-reactive antibodies that will neutralize multiple viral strains.
These results demonstrate that induction of truly broad-spectrum neutralizing antibodies may be an achievable goal.
To be effective, an HIV vaccine must induce the body to produce cross-reactive antibodies that can neutralize multiple strains. USU Professors CAPT Gerald Quinnan, Jr., M.D., USPHS, and Christopher Broder, Ph.D., and their colleagues at USU attempted to elicit these broad-range antibodies in an animal model by immunizing with a particular HIV-1 surface protein, designated R2 gp140, and an immune response-boosting component.
The researchers tested antibodies generated by the immunizations to determine their effectiveness in neutralizing the infectivity of a variety of HIV-1 strains. Antibodies produced as a result of immunization neutralized all 48 strains of HIV-1 tested. The results are encouraging for vaccine development, because they showed that it is possible to elicit a broad-spectrum antibody response.
This research was supported by a grant from a number of collaborators including the National Institutes of Health/NIAID and The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
Crosslinked HIV-1 envelope-CD4 receptor complexes elicit broadly cross-reactive neutralizing antibodies in rhesus macaques (gp120|gp140|gp120-CD4 complex|vaccine)
Timothy Fouts*, Karla Godfrey*, Kathryn Bobb*, David Montefiori, Carl V. Hanson, V. S. Kalyanaraman§, Anthony DeVico*,¶, and Ranajit Pal§
* Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, MD 21201; § Advanced BioScience Laboratories, Inc., 5510 Nicholson Lane, Kensington, MD 20895; California Department of Health Services, 850 Marina Bay Parkway, Richmond, CA 94804; and Department of Surgery, Duke University Medical Center, Box 2926, Durham, NC 27710
Communicated by Maurice R. Hilleman, Merck Institute for Vaccinology, West Point, PA, July 10, 2002 (received for review May 14, 2002)
The identification of HIV envelope structures that generate broadly cross-reactive neutralizing antibodies is a major goal for HIV-vaccine development. In this study, we evaluated one such structure, expressed as either a gp120-CD4 or a gp140-CD4 complex, for its ability to elicit a neutralizing antibody response. In rhesus macaques, covalently crosslinked complexes of soluble human CD4 (shCD4) and HIV-1IIIB envelope glycoproteins (gp120 or gp140) generated antibodies that neutralized a wide range of primary HIV-1 isolates regardless of the coreceptor usage or genetic subtype. Ig with cross-reactive neutralizing activity was recovered by affinity chromatography with a chimeric single-chain polypeptide containing sequences for HIVBaL gp120 and a mimetic peptide that induces a CD4-triggered envelope structure. These results suggest that covalently crosslinked complexes of the HIV-1 surface envelope glycoprotein and CD4 elicit broadly neutralizing humoral responses that, in part, may be directed against a novel epitope(s) found on the HIV-1 envelope.
Another article: “Extensively Cross-Reactive Anti-HIV-1 Neutralizing Antibodies Induced by gp140 Immunization” appears in the Proceedings of the National Academy of Sciences http://www.pnas.org/papbyrecent.shtml.