Co-authored by Margaret I. Johnston, Ph.D., Director of the Vaccine Research Program in NIAID’s Division of AIDS
HIV vaccine development has presented significant challenges for the scientific community. However, in late 2009, we obtained the first clinical evidence that a safe and effective HIV vaccine may indeed be possible. The RV144 Thai trial showed that an experimental “prime-boost” vaccine regimen was safe and 31 percent effective in preventing HIV infection. This information brought renewed hope and optimism to researchers and the HIV/AIDS community. Most recently, the identification by NIAID-led scientists of two new broadly neutralizing human antibodies that can prevent more than 90 percent of known HIV strains from infecting human cells will certainly help to advance HIV vaccine design. As we chart a path forward, we must keep our eye on the goal of developing a safe and effective vaccine that prevents HIV acquisition. To achieve this goal, we are following a two-pronged approach for an HIV vaccine.
The first approach grew out of the 2008 NIAID HIV vaccine summit and consists of a strengthened commitment to basic vaccine discovery for HIV. For example, investigators are actively evaluating the earliest steps during HIV infection and how a vaccine may influence the course of infection. Studies in non-human primates are addressing questions that cannot be addressed in humans. This has resulted in a proliferation of new ideas and concepts to pursue, and we must continue to encourage “out of the box” thinking and approaches to HIV prevention. As these lines of thinking and research progress, we hope that some ideas will mature into novel vaccine concepts worthy of further evaluation. Clearly, an important component of the research endeavor is the eventual evaluation of the most promising new concepts for safety and activity in humans, which includes testing candidate HIV vaccines with acquisition of infection as a clinical trial endpoint.
As we have discussed NIAID’s current HIV vaccine research agenda and potential future directions, please consider the following:
- Are there key components or activities that are missing from our two-pronged approach toward an HIV vaccine?
- Are adaptive trial designs a suitable approach for rapidly evaluating promising HIV vaccine candidates?
- Are there alternative HIV vaccine trial designs that would provide answers quickly and efficiently, so that we can quickly move towards newer, improved products with greater efficacy?
- What mechanisms should be in place to ensure that the HIV clinical vaccine research endeavor integrates product evaluation with scientific inquiry that informs and is informed by vaccine discovery and preclinical efforts?
- What mechanisms would help ensure that the best ideas for vaccine clinical research are identified and implemented?
- Aside from TB, hepatitis C and malaria, are there other infectious diseases that we should focus on for vaccine development in the HIV clinical trial network system?
Second, we need to follow up on the results of the RV144 trial to determine if the results can be extended and improved through clinical trials in higher risk populations and where different strains of HIV circulate. If a measurable sign of how vaccinated study participants were protected — what is known as a “correlate of protection” — is identified through the ongoing studies using RV144 specimens, there will be a relatively straightforward path to the improvement of vaccine design. Absent a correlate, different prime-boost strategies can be evaluated for safety and activity in “proof of concept” trials to yield additional information about what immune responses may or may not correlate with efficacy. One strategy currently under consideration is to use an adaptive trial design so that the vaccine candidates that fail early would be eliminated, resulting in a more streamlined development path. In order for these clinical trials to be performed in an expeditious manner, they will need to be conducted at sites where volunteers at high risk for HIV infection can be rapidly recruited. In addition, clinical trials that enroll volunteers with different routes of potential HIV exposure will need to be developed.
There are a number of other infectious diseases that burden populations impacted by HIV. These include, but are not limited to, tuberculosis, hepatitis C infection, and malaria. Like HIV/AIDS, finding preventive vaccines for these diseases has proven elusive as well. By integrating efforts, the best minds in infectious diseases, vaccine discovery and development can work together, so that the research processes and discoveries for each disease can inform vaccine development for other diseases. Furthermore, integration of efforts to evaluate vaccines against these diseases of public health importance would lead to a more efficient and effective use of clinical laboratory expertise and clinical trial site capacity. Our goal is to have the restructured NIAID HIV clinical trial networks make significant contributions to the development of new preventive vaccines for HIV and other diseases of critical public health importance, including those that impact the most vulnerable populations around the world (e.g., young children and pregnant women). Developing effective preventive vaccines for these diseases will greatly improve the health and well-being of people living in areas with high rates of HIV.
We welcome your thoughts and feedback with regard to this topic. In our next blog post, we will shift the discussion toward the leadership structure for a revamped NIAID HIV clinical trial network system.