Unique Process to Develop Tier-2 Antibodies May Advance HIV Vaccine Research

A new study may represent a promising step in the development of a vaccine for HIV.

The study, conducted by researchers at the Wister Institute, involved the use of a unique trimer to produce tier-2 neutralizing antibodies that may help fight HIV, according to the researchers.

Prior research has found that producing tier-2 neutralizing antibodies with candidate vaccines was inhibited by the process of long and expensive experiments in large animal models, which caused a significant delay in the development of an HIV-1 vaccine.

“With our new finding, we have opened the door to rapid, iterative vaccinology in a model that can produce tier-2 neutralizing antibodies, enabling development of more advanced HIV vaccine concepts,” said study author Daniel Kulp, PhD, associate professor in the Vaccine & Immunotherapy Center at The Wistar Institute, in a press release.

According to The Wistar Institute, the research team encoded the native-like trimer into DNA to infuse the treatment into mice. This process helps in turning the host bodies into “antigen factories,” which allowed them to avoid the complex process of manufacturing vaccines. The researchers then compared the findings from mice who received the DNA-encoded native-like trimer to mice that were administered a standard protein immunization.

The researchers isolated monoclonal antibodies from the mice and used cryo-electron microscopy to evaluate the atomic structure of a single tier-2 neutralizing monoclonal antibody. They discovered that the antibody binds to an epitope, which is a segment of a protein that sticks out of the antigen, called C3V5, according to the study.

Prior research has shown that antibodies binding to C345 protect animals from a SHIV infection, which is closely related to HIV in non-human primates, the researchers noted.

“The structure gives us incredible insight into how this antibody is able to neutralize the virus,” Kulp said in a press release. “For the first time, we can strategize about how to design new vaccines that can generate broadly neutralizing antibody responses to the C3V5 epitope.”

REFERENCE

Wistar Scientists Move HIV Vaccine Research Forward by Developing an Immunogen that Produces Tier-2 Antibodies—the Kind That Matter for Combatting HIV. Wistar Institute. February 4, 2022. Accessed February 4, 2022. https://wistar.org/news/press-releases/wistar-scientists-move-hiv-vaccine-research-forward-developing-immunogen