For the first time, scientists have developed an DNA-encoded immunogen that produces Tier-2 antibodies—the kind that matter for combatting HIV
Nearly four decades after its discovery, HIV has killed 36.3 million people, with no vaccine in sight. Part of the reason vaccine development has been slow is because trialing candidate vaccines that produce Tier-2 neutralizing antibodies—the kind that matter for combatting HIV—has always required long and expensive experiments in large animal models like rabbits and macaque monkeys.
An effective HIV vaccine needs to produce antibodies that protect against the most common variants of HIV, which are categorized as “Tier 2” viruses based on how quickly and easily they can be neutralized by antibodies (more quickly/easily than Tier 3, less than Tier 1).
A new study by scientists at The Wistar Institute shows a quicker, less expensive path to developing this tier of antibodies. For the first time, these scientists have demonstrated a method for eliciting Tier-2 neutralizing antibodies in mice.
“Mice are the workhorse of vaccine design and development because you can iterate lots of concepts in that model due to cost and time constraints,” said Daniel Kulp, Ph.D., associate professor in the Vaccine & Immunotherapy Center at The Wistar Institute.
The scientists developed an immunogen—a substance that causes an immune response—called a native-like trimer, which they administered to mice. Importantly, they encoded the immunogen in DNA, which turns the host bodies (in this case the mice) into “antigen factories” instead of requiring what would otherwise be a complex and expensive vaccine manufacturing process.
They then compared the results from the mice who received the DNA-encoded native-like trimer to results from mice who received a standard protein immunization. Only those mice that received the DNA-encoded native-like trimer developed Tier-2 neutralizing antibodies.
From there, they were able to isolate and examine the atomic structure of one of the antibodies that their immunogen had produced. “The structure gives us incredible insight into how this antibody is able to neutralize the virus,” said Kulp.
“Our data demonstrates the value of this approach as a tool to create surgically tailored immunity against a difficult pathogen’s vulnerable sites, in this case for HIV,” said coauthor David B. Weiner, Ph.D., executive vice president and director of the Vaccine & Immunotherapy Center and the W.W. Smith Charitable Trust Professor in Cancer Research at The Wistar Institute.