The researchers found that the sugars on the natural HIV envelope prevented the envelope from binding to the immature B cell receptors that scientists want to trigger with a vaccine. So human and animal B cells fail to make antibodies against the HIV envelope's vulnerable spots when natural HIV envelope is injected as a vaccine candidate, even though these viral envelopes are the target of protective, neutralizing antibodies.
"We found that when you remove the sugars from the envelope proteins, you can create an envelope that targets those immature B cell receptors," said Haynes, who is also director of the DHVI.
"After the initial results, we completed a study in primates, which are similar to humans in terms of their genetics and their immune systems," Haynes said. "When they were given the HIV outer coat with many of the sugars removed, this sugar-depleted envelope bound better to the immature B cell receptors and stimulated antibodies better, which is a first step in the HIV-1 envelope activating an immature B cell target that previously it could not target."
Dimiter Dimitrov at the National Cancer Institute has previously shown that the natural HIV envelope protein frequently does not target immature B cells.
"The importance of this new finding is that it not only provides evidence for our hypothesis, but also for the first time it has identified envelope-based immunogens capable of binding to putative antibody germline predecessors that correlated with enhanced immunogenicity in animals," Dimitrov said.
Investigators have found that pathways for inducing the "right" kind of antibodies may be blocked or are unusual and are not routinely followed by HIV envelope-indu
|Contact: Mary Jane Gore|
Duke University Medical Center