A novel DNA vaccine developed by UMass Chan scientist Shan Lu shows promising results in preventing HIV infection. The Phase I clinical trial of the polyvalent DNA/prime-protein boost vaccine (PDPHV) demonstrated robust immunogenicity and safety, marking a significant step forward in the decades-long quest for an effective HIV vaccine.
Promising Immunogenicity Results
The clinical trial, led by Ian Frank, MD, at the University of Pennsylvania, involved 60 participants across six U.S. sites. Results published in The Lancet HIV indicated that the PDPHV vaccine elicited strong and cross-reactive immune responses against several HIV subtypes. Notably, all volunteers in the prime-boost group achieved 100% CD4+ T cell responses, a rate not universally observed in previous HIV vaccine studies.
"This is an important milestone and the most robust immunogenicity results ever from a human HIV vaccine study run by the National Institutes of Health’s HIV Vaccine Trial Network," said Dr. Lu. "In order to stem the global tide of AIDS, finding an effective preventive HIV vaccine is our best hope of breaking the transmission cycle. The safety and immunological results from the trial is encouraging progress in this development."
The PDPHV vaccine utilizes a DNA component to prime the immune system, followed by a boost of HIV proteins to stimulate the production of potent antibodies and CD4+ T cells against HIV.
Isolation of Novel Monoclonal Antibody
In a separate study published in Nature Communications, Lu and his team reported the isolation of a novel human monoclonal antibody (HmAb64) from a healthy trial participant who received the PDPHV vaccine. This antibody demonstrated the ability to neutralize HIV isolates across subtypes.
Unlike previous monoclonal antibodies isolated from HIV-infected patients, HmAb64 was derived from a healthy vaccine volunteer. This antibody targets the CD4 binding site on HIV, a critical area the virus uses to invade human CD4+ T cells. The CD4 binding site has been a challenging target for vaccine development due to its complex structure.
"This is the first isolation of a neutralizing CD4 binding site for a human monoclonal antibody with exciting breadth against HIV," said Lu. "Taken from a participant who received our HIV vaccine, this has been an objective for nearly 30 years."
The DNA component of PDPHV primes the immune system to produce antigens that mimic the virus's structure, enabling HmAb64 to effectively neutralize primary HIV isolates across various subtypes. This represents a significant advancement in HIV vaccine development, addressing a long-standing challenge in targeting the CD4 binding site.
