Exciting HIV vaccine research with bNAbs overcomes key obstacle

HIV vaccine bnabs iavi tsri vrc01 eod-gt6 (patsy lynch)

A new technique for vaccine design may help overcome an important obstacle in developing a vaccine against HIV. Researchers at The Scripps Research Institute (TSRI) and the International AIDS Vaccine Initiative (IAVI) were able to use the novel technique to, for the first time, stimulate immune cells that can produce broadly neutralizing antibodies that can protect against a wide range of viral strains. The research was published in Science Express.

A major challenge in developing a vaccine against HIV is the ability of the virus to readily change its genetic make-up. HIV is thus a highly variable virus, and able to continuously evade targeting by the immune response. However, researchers have also known that a minority of HIV-positive people are able to produce broadly neutralizing antibodies (bNAbs) against a wide range of HIV variants (IAVI). Researchers have hoped that if a vaccine could induce B cell production of bNAbs before HIV exposure, then this could prevent infection with HIV.

For the past few years, vaccine researchers have been on the hunt for such antibodies in HIV-positive volunteers around the world, and have identified several antibodies with broad and potent neutralizing activity. One such bNAb, VCR01, has been shown in the laboratory to neutralize more than 90% of HIV variants (IAVI).

However, a further difficulty lies in developing a vaccine that can elicit bNAb production in the body. Ideally, a vaccine against HIV would stimulate germline B cells to produce bNAbs. However, wild-type HIV envelope proteins fail to bind to and stimulate the germline B cells that are precursors of bNAb-producing cells. Effectively, there is an early obstacle in place preventing the whole process from getting started.

In this most recent study, researchers engineered an artificial immunogen that was able to overcome the hurdle of stimulating germline B cells with HIV protein. The researchers whittled down the HIV envelope protein to the most minimal form that could be recognised by the VRC01 bNAb. The result was a tiny yet highly optimized immunogen called eOD-GT6. They then shaped 60 copies of eOD-GT6 into a virus-like particle, and this was shown to be effective at potently activating the germline B cells of interest.

“We have overcome the first obstacle to elicit one type of anti-HIV broadly neutralizing antibodies through vaccination,” said Andrew McGuire, Seattle BioMed, in a press release.

The researchers hope to test the ability of eOD-GT6 nanoparticles to stimulate an antibody response in animals that are engineered to produce human germline antibodies, before preparing the approach for trial in humans.

Do you think that eliciting bNAb production is a promising strategy? Do you think that the generation of the eOD-GT6 immunogen is a significant step towards a vaccine against HIV?

Click here for the IAVI press release, TSRI press release, and Seattle BioMed press release. The journal article can be found here.

You can join our discussion on LinkedIn or leave a comment below, I'd love to hear what you think. You can read more about exciting advances in HIV prevention in this free downloadable presentation, and more about novel vaccine combinations towards an HIV vaccine. More about HIV: Research success against SIV may lead the way for HIV vaccine

If you're interested in hearing more about strategy and innovation in vaccines, including a talk on novel approaches to HIV vaccine design, you might like to consider attending the World Vaccine Congress and Expo 2013 on the 16-18 April 2013, Gaylord National Hotel and Convention Center, Washington DC. You can download the brochure here.

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