February 28, 2014

IAVI Excited About Progress That Detailed Picture of HIV Envelope Protein Can Bring to Fight Against AIDS

NEW YORK – The International AIDS Vaccine Initiative (IAVI) congratulates the researchers from The Scripps Research Institute (TSRI) and Cornell University for their landmark findings published in Science, describing the structure of the outer part of the HIV trimer, the tripartite HIV Envelope protein.

IAVI is proud to have supported this research together with the National Institute of Health (NIH)*, among others. “These findings have collectively achieved a major, decade-long goal of AIDS vaccine research and are likely to advance and accelerate the design of vaccines to elicit broadly neutralizing antibodies against HIV,” said IAVI Chief Scientific Officer Wayne Koff.

Broadly neutralizing antibodies (bNAbs), if elicited by a vaccine, could prevent infection by a broad range of HIV’s many variants, and the Envelope protein is the sole target available to these antibodies. There are many challenges to the design and testing of such a vaccine, including the great sequence diversity and instability of the Envelope protein. Having in hand a stable trimer mimic and detailed information about its structure are major steps forward in vaccine design.

One study by Dmrity Lyumkis et al. from the laboratories of TSRI’s Bridget Carragher, Ian Wilson and Andrew Ward used electron microscopy to reveal the structure of a trimer stabilized and isolated in John Moore’s laboratory at Cornell University. A parallel study by Jean-Philippe Julien et al., also from the laboratories of Moore, Ward and Wilson, applied X-ray crystallography to detail the full structure to atomic level. These studies come on the heels of another study led by the Moore laboratory, published last week in the Proceedings of the National Academy of Sciences, that describes in detail the properties of the stable trimer used in the Lyumkis and Julien studies.

The stable trimer has been engineered in a multi-laboratory collaboration, including the Moore group at Cornell as well as groups from IAVI’s Neutralizing Antibody Consortium (headquartered at the Neutralizing Antibody Center at TSRI) and the IAVI Design and Development Laboratory (DDL). IAVI is now working with Moore and his colleagues to test and advance to development the trimer as a possible immunogen in an AIDS vaccine that can induce broadly neutralizing antibodies.

IAVI is also enthusiastic about landmark research published in Nature by Dan Barouch et al. of the Beth Israel Deaconess Medical Center, as well as scientists at TSRI. Barouch and colleagues showed that neutralizing antibodies can have a strong therapeutic effect in rhesus monkeys infected with a hybrid simian-human immunodeficiency virus (SHIV). The effect can be induced by a single antibody such as PGT121, which was isolated by researchers in IAVI’s NAC in collaboration with Theraclone, Monogram Biosciences and based on the Protocol G project, a global search for broadly neutralizing antibodies in blood samples from people living with HIV that was orchestrated by IAVI and the NAC.

“Together, these reported successes illustrate the immense promise of broadly neutralizing antibodies in the fight against HIV and AIDS,” said Koff. “They also confirm the importance of long-term vision, persistence and collaboration in the quest to develop an AIDS vaccine.”

*More specifically the Division of AIDS (DAIDS) at the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of General Medical Sciences (NIGMS) Biomedical Research Technology Program