Biology scientists have created a novel antibody treatment that can deactivate a wide range of HIV-1 strains. Surprisingly, the breakthrough came from llamas.
A team of researchers at Georgia State University has developed small but powerful molecules capable of pinpointing hidden strains of HIV. These molecules are derived from antibody genes found in llama DNA.
The study, led by Assistant Professor Jianliang Xu, utilizes llama-derived nanobodies to effectively neutralize multiple strains of HIV-1, the predominant form of the virus. The team’s latest findings have been published in the journal Advanced Science.
Xu explained, “This virus has evolved mechanisms to evade our immune system. Traditional antibodies are cumbersome, making it challenging for them to locate and attack the virus’s surface. These new antibodies have a more efficient approach.”
Researchers have been exploring camelid family animals like llamas for approximately 15 years in the quest for effective HIV treatments and prevention. Their antibodies’ structure and characteristics enable them to efficiently identify and deactivate foreign entities such as the HIV virus.
This recent research introduces a broadly applicable technique to enhance the efficacy of nanobodies. Nanobodies are specialized antibody fragments approximately one-tenth the size of conventional antibodies. They are crafted from flexible, Y-shaped heavy chain-only antibodies comprising two heavy chains, which have demonstrated higher effectiveness in combatting specific viruses compared to standard antibodies with light chains.
The nanobodies are derived from agile, Y-shaped antibodies composed of heavy-chain peptides, potentially offering increased potency against certain viruses.
For the study, llamas were immunized with a custom protein to trigger the production of neutralizing nanobodies. Xu’s team pinpointed nanobodies capable of targeting vulnerable spots on the virus. When the nanobodies were engineered into a triple tandem structure by duplicating short DNA segments, they exhibited exceptional efficacy by neutralizing 96% of diverse HIV-1 strains.
Further investigation revealed that these nanobodies imitate the recognition of the CD4 receptor, a critical element in HIV infection. To enhance their strength, the nanobodies were fused with a broadly neutralizing antibody (bNAb), resulting in a novel antibody with unparalleled neutralizing capabilities.
Xu noted, “Instead of developing a blend of antibodies, we can now create a single molecule capable of neutralizing HIV. By working with a broadly neutralizing nanobody that can deactivate over 90% of prevalent HIV strains and combining it with another bNAb which also neutralizes about 90%, we can achieve close to complete neutralization.”
Initiating this research at the National Institutes of Health Vaccine Research Center in Bethesda, Maryland, Xu collaborated with a group of more than 30 researchers, including Peter Kwong, a biochemistry and molecular biophysics professor at Columbia University and study co-author. Since joining Georgia State in 2023, Xu has been guiding Payton Chan, a Ph.D. candidate at Georgia State, as they work to expand the potential applications of these solutions.
Chan expressed enthusiasm for the groundbreaking research’s promising prospects.
“These nanobodies are the most potent and effective neutralizing antibodies to date, which bodes well for the future of HIV treatment and antibody research,” Chan remarked. “I envision a future where these nanobodies gain approval for HIV treatment.”
According to Xu, forthcoming endeavors will investigate the potential of combining llama nanobodies with other existing bNAbs to ascertain whether certain combinations can achieve 100% neutralization, offering novel treatment avenues in the battle against HIV.
