Abstract

Promising vaccine trials and recent advances in basic scientific understanding of HIV immunology suggest that a highly efficacious preventive vaccine will appear in the near future. However, it cannot be assumed that the availability of an efficacious vaccine will ensure a population's uptake, given the array of potential psychosocial, cultural and political barriers. Research that examines these barriers has tended to be conducted in North America. Moreover, communities of FSWs and MSM who encountered numerous barriers to health services are noticeably absent from this body of research. For this reason, the proposed project will examine the acceptability of a future HIV vaccine among highly stigmatized MSM and FSWs, as well as members of civil society organizations engaged in HIV prevention work within these communities. This project will be conducted at four culturally contrasting sites in Asia and Africa. 

Abstract

Since the publicity of the failed Merck Step trial, there has been a useful change in Vaccine research to consider more subtle but important issues. We rank two factors at the top to achieve success at preventing HIV infection through vaccination: The timing (earliest), and the targeting (mucosal) of the immune response are issues of importance and precision. We propose to capitalize more on the early warning systems (innate immunity) that that triggers the immune system (cellular and antibody) to respond against invading HIV at exactly the time of entry at the mucosa site rather than waiting until the virus expands and gets to the blood. This provides the rationale for this team grant. A successful HIV vaccine must stimulate both the antibody and cellular arms of the immune system, both in the blood (systemically) and at the mucosal level. That is achieved through the use of immune stimulator molecules based on the principles and molecules of innate immunity and its regulatory properties. We plan to test in the SIV monkey model, Cytomegalovirus, a virus similar to herpes virus as an HIV vaccine vector that can provide long term mucosal immune cells that are always ready to strike. The rationale is that it these early strikers can attack right at entry when the virus is most vulnerable unlike other vaccines which provide immune cells that wait in the lymph node until the invading virus gets there and has multiplied. Both antibody and cells are needed to immobilize HIV at the mucosa. We plan a novel approach to the generation of mucosal neutralizing (virus killing) antibody against HIV. Using novel structural and molecular biology techniques we will build and then test a DNA vaccine which we can then vaccinate to produce a combination of the full-size trimerized HIV Envelope with an immune-regulator molecule as a trimer in three projections. We will test if this more stable structure will result in neutralizing antibody. 

Abstract

The discovery of a safe and effective preventive vaccine is the best hope for controlling the global AIDS epidemic. To that end, clinical trials involving thousands of human volunteers will need to be conducted for the foreseeable future. Efficacy trials (to determine if a vaccine is effective in preventing HIV infection or not), in particular, involve high-risk volunteers often from vulnerable communities, including the developing world. The objective of this international, interdisciplinary and participatory research program is to identify and mitigate social, behavioral and health risks among volunteers and potential volunteers in HIV vaccine trials in Canada, India, Kenya, South Africa and Thailand. The purpose of the research program is to build an evidence base to ensure the highest standards of care and prevention in safe, ethically and justly conducted HIV vaccine trials.

Abstract

We propose to develop and validate a highly innovative, process for producing a prophylactic HIV vaccine. The biggest hurdle to an effective vaccine is HIV's extreme genetic diversity, which makes it impossible to anticipate the viral variants that will infect a given individual. We have observed that HIV diversity is unusually limited among injection-drug users (IDUs), and speculate that it is most limited among IDUs who are socially related. We propose to identify IDUs whose viruses are highly similar, and to determine the extent to which their immune responses will suppress each other's viruses. Based on this, we plan to identify social networks of IDUs who share well-defined viruses, and to produce and test a vaccine for them. This work will to lead to a clinical vaccine study to identify correlates of protective immunity, and from which a broadly protective vaccine could be developed.

Abstract

Over 2 million HIV exposed but uninfected newborns (HEU) are born every year. Most develop an immune response to HIV that remains detectable for years. This immune response is presumed to contribute to their protection from vertical HIV transmission around birth. But what role this immune response has on the risk for contracting HIV horizontally later in life has never been examined. We propose to develop and test strategies to reach HEU subjects in order to identify the prevalence of HIV infection in adolescent/adult HEU, and to initiate prospective studies aimed at identifying the responsible mechanisms (correlates of protection). As the maturation of the ongoing AIDS pandemic catapults this vulnerable age group into the spotlight in an era where the stigma associated with HIV still is overwhelming, developing effective and ethical tools to reach this population constitutes the necessary first step to not only extract guidelines for future vaccine design, but also to provide optimal care