GSID: Our Programs

• Global Public Health Surveillance Systems

“A Path to an HIV Vaccine”

Although considerable progress has been made in developing drugs to treat existing HIV infections, much less progress has been made in developing a vaccine to prevent infections altogether. With an estimated 14,000 new HIV infections each day worldwide, most experts agree that a safe and effective vaccine solution is needed to halt the pandemic spread of this dangerous virus.

Our initial project will be to capture as much knowledge as possible (genetic, virologic, and immunologic) from the invaluable clinical samples and data gathered during the Phase III clinical trials conducted by VaxGen (Brisbane, CA) between 1998 and 2003. Under the leadership of GSID’s founders, the VaxGen studies were the world’s first and only completed Phase III efficacy trials for an HIV vaccine. By gaining a better understanding of the structure of the virus and its genetic sequence, we should be able to better identify potential antigens to include in a new vaccine candidate.

GSID believes the failure to develop an effective vaccine can be attributed to five major problems: 1) antigenic variation of the virus; 2) lack of understanding of the structure and polymorphisms of viruses that mediate transmission; 3) lack of understanding of the epitopes recognized by virus neutralizing antibodies in the serum of HIV infected individuals; 4) inability to simultaneously induce antibody and CTL immune responses (TH1 and TH2) to the key antigenic structures responsible for protective immunity; and 5) genetically determined host factors that regulate the magnitude and quality of the anti-HIV immune response.

For this program we have assembled a consortium of investigators who will apply new technologies, resident in the biotechnology industry and, specifically, the genomics and the proteomics fields, to the five key problems in AIDS vaccine development listed above. We will apply these technologies to the unique collection of clinical specimens assembled in the course of the world’s first large scale HIV vaccine efficacy trials conducted by VaxGen, Inc. These specimens represent the largest and most up-to-date collection of viruses from early infections ever assembled along with unprecedented clinical data associated with each sample. Virtually all previous vaccine development efforts have relied on viruses from persistent infections or laboratory isolates collected years after the time of transmission. Considerable evidence exists to suggest that viruses that mediate transmission are different from those that mediate disease. In this context, this collection of specimens will allow us, for the first time ever, to characterize the chemical and biological properties of viruses that mediate new infections.

Specifically, we will: 1) establish a web-accessible sequence database and specimen repository of transmission viruses; 2) define the most common sequence and structural polymorphisms among transmission viruses and establish a representative panel of transmission viruses and virus genes for use in neutralization studies and new vaccine antigen development; 3) carry out neutralization and epitope mapping studies utilizing polyclonal and monoclonal antibodies to characterize broadly neutralizing antibodies seen in about 30% of HIV+ infected people; and 4) carry out a genetic analysis of host factors that affect the susceptibility and/or resistance to HIV infection. Through these accomplishments, we aim to advance the global effort for identifying new, safe, and effective HIV vaccine candidates.

Global Public Health Surveillance Systems

Surveillance has historically been an important tool of public health and disease control, and recent developments in information technology have allowed public health officials to monitor information from a multitude of media sources. By scanning news reports and websites for stories of public health interest, for example, early warning systems have been developed to help public health officials respond more quickly to and manage infectious disease outbreaks around the world.

Given our experience in global public health and our interest in developing tools for the control of infectious diseases, GSID was retained to research the field of informal surveillance networks and to develop a detailed business plan to enhance and improve the operations of the Global Public Health Intelligence Network (GPHIN), which was originally developed by the Public Health Agency Canada (PHAC). Support for this project was funded through the Silicon Valley Community Foundation.

Pediatric Dengue Vaccine Initiative

Dengue fever is a mosquito-borne disease, primarily of children and is prevalent in tropical countries around the world and can become a vaccine preventable disease. Dengue fever has severe consequences of hemorrhagic fever and dengue shock and results in substantial morbidity and mortality. GSID’s expertise in clinical and product development has been utilized by PDVI, a program of the International Vaccine Initiative in Seoul, Korea, in evaluating candidate vaccines, their respective developers and potential manufacturing partners. Our evaluations of development partners have provided PDVI with the necessary input to further the advancement of evaluating dengue vaccines in large-scale trials.