Shan Lu, MD, PhD, professor of medicine, has received $17.3 million from the National Institute of Allergy and Infectious Diseases (NIAID) to develop and produce an optimized HIV vaccine to be used in Phase II human clinical trials. The seven-year program builds on two decades of scientific progress by Dr. Lu, a leader in HIV vaccine research, and marks a major milestone in the field of HIV vaccine development.
“We’ve made incredible progress in developing a cocktail of antigens capable of producing antibodies using our ‘prime-boost’ method,” said Lu. “Establishing processes and protocols that can be scaled up for manufacturing purposes represent the next stage in producing a viable vaccine that can be taken to a large scale clinical trial.”
Funding for the project will be used to standardize and validate production of the vaccine. The goal is to create a manufacturing process to produce enough vaccine for several hundred volunteers in a Phase II clinic trial. If the trial is successful, the process could be used to accommodate production of several thousand doses for the next step, a Phase III clinical trial.
AIDS is one of the worst pandemic diseases in modern times; approximately 1.1 million people died from the disease last year and another 2.1 million contracted the virus (UNAIDS 2016). HIV attacks vital cells in the human immune system, causing it to weaken and fail. As a result, patients with the virus develop AIDS and are susceptible to life-threatening opportunistic infections associated with the progressive failure of the immune system.
The United Nations recently announced a goal of ending the spread of the disease by 2030. Currently, there is no vaccine available to prevent HIV infection. Anti-retroviral therapy can control the progression of AIDS but cannot cure or stop the spread of the virus. Historically, vaccines have been tremendously successful in halting the advance of infectious diseases such as smallpox, polio, measles and yellow fever. By presenting a foreign antigen to the immune system in healthy individuals, vaccines are able to stimulate production of antibodies ready to fight the pathogen prior to infection. Similarly, HIV vaccines represent the best long-term hope for ending the HIV pandemic, and HIV vaccine research is a top priority for NIAID.
Lu has taken the novel approach of combining a DNA vaccine developed by his lab with a recombinant protein-based vaccine, such as the type used for human papillomavirus (HPV). The HIV DNA acts as a primer to turn on the immune cells and is followed by a booster shot of the HIV protein vaccines, which stimulates production of the antibodies that fight the virus. This two-part approach activates both antibody and cell-mediated immune responses, and induces functional antibodies with better qualities and longevity than using either type of vaccine alone.
“The immune system uses B-cells to produce the antibodies that fight viral invaders,” said Lu. “The HIV DNA bits drag the B-cells out of sleep. We then expose the B-cells to specific HIV envelope proteins that are some of the most susceptible parts of the virus, so they can start producing antibodies that target these vulnerabilities. This prime and boost combination gives the immune system the added jolt it needs to produce enough antibodies to fight the virus.”
In the past several years, Lu and his team has successfully produced this novel HIV vaccine for a Phase I clinical study. The current funding will be used to further optimize the vaccine, which consists of four separate HIV envelope proteins selected for their ability to elicit broad neutralizing antibodies, as well as simplifying the purification and manufacturing process. UMass Medical School will work with Waisman Biomanufacturing, affiliated with the University of Wisconsin, to manufacture the vaccine for Phase II clinical trials.
“In order to stem the global tide of AIDS, finding an effective preventive HIV vaccine is our best hope of breaking the transmission cycle” said Lu. “This funding brings promising new research into an HIV vaccine one step closer.”
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