Alternative Strategy For HIV Vaccine

Main Category: HIV / AIDS
Also Included In: Immune System / Vaccines
Article Date: 23 May 2008 - 4:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

Advanced BioScience Laboratories, Inc. (ABL) and the University of Massachusetts Medical School (UMMS) report that their unique HIV vaccine formulation was effective in eliciting strong and balanced immune responses in healthy human volunteers. The findings are published in the journal Vaccine ("Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime-protein boost HIV-1 vaccine in healthy human volunteers," Vaccine online, May 22, 2008) In light of these initial findings, additional assays on volunteers' samples were done by researchers at the University of Alabama at Birmingham, independently confirming the presence of long lasting and high quality T cell responses against HIV antigens. Results from this confirmatory study are currently available online in the Journal of Virology (April 30, 2008).

In this phase I clinical trial, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), volunteers first received three injections of a DNA vaccine which expresses protective antigens from the HIV virus, followed by two injections of a protein vaccine whose components matched those included in the DNA vaccine. The report in Vaccine is the first scientific article in which a "DNA prime-protein boost" combination vaccination method is tested in humans for HIV vaccine development. Scientists at ABL and UMMS and their collaborators discovered that this combination approach is highly effective in inducing strong antibody and cell-mediated immune responses in human volunteers.

"Given the challenges of developing a vaccine against HIV, scientists have long believed that a final, effective HIV vaccine will require the induction of balanced responses from both arms of human immune system. Our results demonstrate that it is feasible to use this combination approach to achieve this objective," said Phillip Markham, PhD, of ABL, the Principal Investigator (PI) on this vaccine development effort, performed under contract to the NIAID.

One unique design underlying this combination HIV vaccine formulation is the use of a "cocktail" of five different envelope (Env) proteins collected from HIV viruses circulating in different parts of the world. Env is a key protective antigen and the goal was to elicit broad antibody responses against a wide range of HIV viruses in order to counter the issue of frequent HIV mutations. Indeed, the high titer antibodies found in volunteers' sera were able to recognize each of a very diverse group of Env antigens that were included in this study. More significantly, the majority of volunteers developed positive neutralizing antibodies against a good portion of the five HIV subtypes included in the assay.

Shan Lu, MD, PhD, professor of medicine and biochemistry & molecular pharmacology at the University of Massachusetts Medical School and the co- Principal Investigator (co-PI) of the vaccine development program, describes the finding of neutralizing antibodies in this study as "a major step forward."

"Previously, we didn't know where to start. The neutralizing antibody titers in our study are still relatively low, but, these results are promising and open the door for future efforts to optimize HIV vaccine formulations in order to achieve a protective HIV vaccine," said Dr. Lu.

The dominant approaches in the current HIV vaccine field rely on viral vector-based delivery systems, an approach that produced disappointing results in a recent efficacy trial. Drs. Markham and Lu believe their HIV vaccine strategy will offer an alternative approach to focus on the induction of protective antibodies for HIV vaccine development, while maintaining strong cell-mediated immune responses. In addition to NIH, the International AIDS Vaccine Initiative (IAVI) also provided funding support to part of the study. Researchers from Duke University Medical School also participated, as did Dr. Paul Goepfert at the University of Alabama-Birmingham.

----------------------------
Article adapted by Medical News Today from original press release.
----------------------------

About the University of Massachusetts Medical School

The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $179 million in research funding annually, 80 percent of which comes from federal funding sources. The work of UMMS researcher Craig Mello, Ph.D., an investigator of the prestigious Howard Hughes Medical Institute (HHMI), and his colleague Andrew Fire, Ph.D., then of the Carnegie Institution of Washington, geared toward the discovery of RNA interference was awarded the 2006 Nobel Prize in Physiology or Medicine and has spawned a new and promising field of research with potential for an astounding global impact. UMMS is the academic partner of UMass Memorial Health Care, the largest health care provider in Central Massachusetts. For more information, visit http://www.umassmed.edu/.

About Advanced BioScience Laboratories, Inc (ABL)

ABL is a Maryland biomedical research firm dedicated to conducting research and providing resources to develop and evaluate vaccines, therapeutics and diagnostics for infectious agents for the biomedical community. ABL is a highly skilled contract research organization (CRO) having extensive experience working with government and commercial entities and other groups, including academic institutions. ABL is committed to delivering quality services that advance HIV and other infectious disease research for the public good. ABL can help with all aspects of product development including basic research, vaccine or product design, animal model studies including immunological and virological monitoring, cGMP manufacturing of biologics for phase I and II clinical trials, and many other services. For more information please visit http://www.ablinc.com/

Source: Office of Public Affairs
University of Massachusetts Medical School