“Many of these candidates will very soon go into humans, in Phase I trials,” said Director Anthony Fauci. But he warned HIV vaccinology is still very much in the discovery phase and it’s impossible to even rank lead candidates.
“HIV is very strange, because it does not induce a protective response in people. It can induce some response, not a particularly good one, and it usually takes two or more years and only happens in a minority of people infected with HIV [20 per cent],” he said. “So the body itself doesn’t provide you with a particularly good roadmap to develop a vaccine.”
Though there have been some trials of vaccine candidates, Fauci believes understanding broadly neutralising antibodies offers the most hope for approval. Writing in Science, he noted that a pragmatic vaccine approach will likely require induction of bNAbs by active immunisation.
A range of bNAbs has been characterised and Fauci’s institute has supported investigators in many universities and institutes. “It is less companies right now than individual scientist at different universities throughout the [US] and the world. My institute funds many of the people working on this.”
In his paper, he writes: “Several recent findings have advanced the field. First, the epitopes to which the bNAbs bind have been characterised in detail; in fact the envelope trimer itself has been stabilised in a soluble form and might be a suitable immnogen. In addition, B cell lineages have been defined and the cellular and evolutionary process necessary to create such antibodies has been characterised.”
He says it’s a question of proper conformational engineering of the envelop molecule so as to stimulate just the right immune cells in the body.
“You can take out the cells that make the antibodies from the patient, molecularly clone them and study them very carefully,” he explained. “Human trials are likely soon.”
The challenge is to develop a product that induces a response that is even better and quicker than the natural infection: “this is a huge scientific challenge, but if we do it we will wind up getting a good vaccine, but we are not there yet by any means.”
“Once you get a vaccine that works, I don't see any problem in manufacturing it. That is the least of our problems,” he adds.
Fauci believes T cells will also play a role, but not on their own: “Ultimately we are going to have to induce these neutralising antibodies.”