Georgia State University researchers have created small, powerful compounds that can specifically target HIV strains that are concealed. Created from Llama DNA antibody genes.
Under the direction of Jianliang Xu, an assistant professor of biology, the research used llama-derived nanobodies to comprehensively neutralise a variety of HIV-1 strains, which is the most prevalent type of the virus.
Their findings were published in the journal Advanced Science.
This virus has evolved a way to escape our immune system. Conventional antibodies are bulky, so it’s difficult for them to find and attack the virus’ surface,
These new antibodies can do this in an easier way.
Jianliang Xu
Researchers have been studying animals of the camelid family, such as llamas, to develop efficient HIV treatment and preventive strategies for the past fifteen years. This is because the structure and characteristics of their antibodies enable them to recognise and neutralise foreign substances, such as HIV, with greater agility.
This new study offers a broadly useful technique to improve nanobodies’ performance. Artificially created antibody fragments, known as nanobodies, are around 10 times smaller than regular antibodies. They come from Y-shaped, flexible heavy chain-only antibodies, which are composed of two heavy chains and are more powerful against some viruses than traditional light-chain antibodies.
To produce neutralising nanobodies, a specifically developed protein was used to immunise llamas for the investigation. Next, Xu and his colleagues discovered nanobodies that can specifically target the virus’s weak points. By repeating brief segments of DNA, the scientists were able to modify the nanobodies into a triple tandem configuration, which resulted in nanobodies that were remarkably successful in neutralising 96% of a panel of HIV-1 strains.
Subsequent investigation revealed that these nanobodies imitate the way the HIV virus recognises the CD4 receptor, which is important. The nanobodies were combined with a widely neutralising antibody (bNAb) to increase their effectiveness, creating a novel antibody with hitherto unheard-of neutralising capabilities.
Instead of developing a cocktail of antibodies, now we can make a single molecule that can neutralize HIV,
We are working with a broadly neutralizing nanobody that can neutralize over 90 percent of the circulating HIV strains, and when we combine that with another bNAb which also neutralizes some 90 percent, together, they can neutralize close to 100 percent.
Jianliang Xu
At the National Institutes of Health Vaccine Research Centre in Bethesda, Maryland, where he worked with a group of around thirty scientists, Xu started this study. Co-author of the paper and Columbia University professor of biochemistry and molecular biophysics Peter Kwong was part of the team. Xu has been a mentor to Payton Chan, a Ph.D. candidate at Georgia State, since he arrived in 2023. They are collaborating to increase the range of these possible treatments.
These nanobodies are the best and most potently neutralizing antibodies to date, which I think is very promising for the future of HIV therapeutics and antibody research,
I hope one day there will be approval of these nanobodies for the treatment of HIV.
Jianliang Xu
To provide new therapeutic options in the battle against HIV, Xu states that future research will investigate the possibility of mixing llama nanobodies with other already available bNAbs to see whether any of these combinations can reach 100% neutralisation.
Source: Georgia State University – Research Magazine
Journal Reference: Xu, Jianliang, et al. “Ultrapotent Broadly Neutralizing Human-llama Bispecific Antibodies against HIV-1.” Advanced Science, vol. 11, no. 26, 2024, p. 2309268, https://doi.org/10.1002/advs.202309268.
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