Timing is Everything in Delivery of HIV Vaccine Candidate

Optimal mode and timing of vaccine delivery is crucial to the success of an HIV vaccine candidate, scientists say.

Although the treatment landscape for HIV changed drastically following the emergence of antiretroviral therapy, there is still no cure. AVERT estimates that 36.7 million individuals around the globe are living with HIV and 40% are unaware of their status.

Scientists continue to search for new ways to develop a safe and effective vaccine against the virus. In a study published in Immunity, investigators demonstrated the importance of optimizing the model and timing of vaccine delivery to reliably induce a neutralizing antibody response.

The results of the study showed that administering the vaccine candidate subcutaneously and increasing the time intervals between immunizations improved the efficacy of the vaccine and reliably induced neutralizing antibodies.

“This study is an important staging point on the long journey toward an HIV vaccine,” said investigator Dennis R. Burton, PhD. “The vaccine candidates we worked with here are probably the most promising prototypes out there, and one will go into people in 2018.

“There had been a lot of big question marks and this study was designed to get as many answers as possible before we go into human clinical trials. We are confident that our results will be predictive going forward.”

The findings are based on prior research of artificial protein trimers that mimic a protein spike found on the viral surface.

Earlier and smaller studies conducted in non-human primates showed that these recombinant trimers were unreliable.

“The animals’ immune responses, although the right kind, weren’t very robust and a few didn’t respond at all,” said investigators Colin Havenar-Daughton, PhD. “That caused significant concern that the immunogen wouldn’t consistently trigger an effective immune response in all individuals in a human clinical trial.”

Through a collaborative effort, the investigators tested multiple variations of the trimers and immunization protocols side-by-side to determine the best strategy for reliably inducing a neutralizing antibody response.

The study design was largely influenced by findings from a prior study, in which scientists observed that follicular helper T cells helped guide the maturation steps of antibody-producing B cells.

By administering the vaccine candidate subcutaneously rather than through intramuscular injection, and spacing the timing of injection to 8 weeks, the investigators could reliable induce a functional immune response in all study animals.

The most successful method was through an osmotic pump that slowly released the vaccine over a 2-week period and produced the highest neutralizing antibody titers ever measures in non-human primates.

The authors noted that osmotic pumps are impractical but “depending on how we gave the vaccine, there was a bigger difference due to immunization route than we could have predicted,” said co-lead author Matthias Pauthner. “We can help translate what we know now into the clinic.”