• About
• Global Efforts
  • Global Program Strategy
  • Threat Assessment
  • International Site Approach
• Vaccine Research and Development
• Prevention, Care and Treatment
• Clinical Trials
• Partners & Links

Global Program Strategy

The goal of the HIV research program is to develop effective countermeasures to protect U.S. Military forces against HIV/AIDS. The primary focus is on developing a globally effective preventive HIV-1 vaccine.

Epidemiology studies to define the global threat and to assess the likelihood that candidate vaccines will provide broad protection is a key part of this global strategy.

Subtypes

Evidence shows that 90-95% of the HIV-1 circulating globally contain sequences from subtypes A, B, C and D. Subtypes B and D are closely related and, by modern phylogenetic criteria, form major branches of a single subtype. Thus, these four subtypes can be distilled to subtypes A, C, and D.

The USMHRP strategy is to match tested vaccines to circulating HIV-1 variants in the intended vaccine testing population using vaccines comprising sequences from subtypes A, C and D.

Vaccine Strategy

The Program's goal is to develop a successful vaccine that would induce both cytotoxic T-lymphocyte response in greater than 50% of vaccine recipients and/or HIV-specific antibodies with in vitro neutralizing capacity against primary HIV-1 isolates.

No vaccines currently induce broadly reactive and potent neutralizing antibodies against circulating strains of HIV. Although vaccines, which induce cellular immunity, provide protection from disease progression in animal models, there is no consensus as to which biomarkers correlate with protection from disease acquisition or progression.

Deductive analysis of human immune responses in vaccine efficacy trials, particularly those studies with some level of protection from infection or disease progression, would provide the least unambiguous source of data to help vaccine development. Execution of these efficacy trials is the cornerstone of the program's strategy.

The USMHRP vaccine development approach utilizes molecular platforms to determine vaccine product selection by examining the relationship between the HIV-1 subtype of vaccine products and the HIV-1 subtype of vaccine testing populations.

Genetics and Host Factors

One of the Program's basic approaches includes the study of the genetics of host restriction and viral defense in populations that may participate in vaccine trials. All human genetic factors that are currently known or subsequently identified during the course of this program that can influence HIV-1 infection or disease progression, including host restriction factors and certain Killer Immunoglobulin Receptors (KIR) of the innate immune system, will be evaluated. Parallel study of polymorphisms in viral genes that defend against host restriction will define HIV-1 variation resulting from selection by host restriction and innate immunity.

Pre-clinical Studies

The pre-clinical vaccine development strategy helps define safety, humoral immunogenicity (especially primary isolate neutralizing antibody testing), and cellular immunogenicity in possible vaccine candidates. Techniques include ELISpot, intracellular cytokine staining, 51Cr release cytotoxic T lymphocyte (CTL), lymphoproliferative assays and multiparameter flow cytometry in testing vaccine products.

Clinical Studies

Vaccine clinical research also is a major component of the USMHRP global strategy. Conducting a series of Phase I through Phase IIb studies of preventive HIV vaccine candidates is a critical part of the scientific pathway to determine a safe and effective vaccine for many different populations.

USMHRP International Network:
Nigeria | Kenya | Tanzania | Uganda | Thailand