by Eva Schissler,University of Cologne

Ultralong 11-amino-acid insertion facilitates the quaternary binding mode of 04_A06. Credit:Nature Immunology(2025). DOI: 10.1038/s41590-025-02286-5

An international research team led by the University of Cologne has discovered an antibody that could advance the fight against HIV. The newly identified antibody 04_A06 proved to be particularly effective in laboratory tests. It was able to neutralize 98.5% of more than 300 different HIV strains, making it one of the broadest antibodies against HIV identified.

In experiments with humanized mice—animals whose immune system has been modified to resemble that of humans—04_A06 permanently reduced the HIV viral load to undetectable levels. Most other HIV antibodies, in contrast, only achieveshort-term effectsin thisanimal model, as resistance develops quickly. The study "Profiling of HIV-1 elite neutralizer cohort reveals a CD4bs bNAb for HIV-1 prevention and therapy" ispublishedinNature Immunology.

Antibodies are protein molecules of the immune system that specifically attack pathogens. Identifying an effective HIV antibody is a known challenge, given that the virus is constantly changing. As a result, many antibodies can only block certain variants of the virus.

For the current study, the researchers examinedblood samplesfrom people referred to as "elite neutralizers," whose immune system fights the virus with particular effectiveness. The researchers produced more than 800 antibodies from more than 5,000 individual so-called B lymphocytes and tested their effectiveness.

One stood out: antibody 04_A06 surpassed all others in terms of potency and breadth as determined by neutralization assays.

"With 04_A06, we have discovered an antibody that not only has an exceptionally broad activity, but also overcomes the virus's typical resistance mechanisms. This could open up a promising approach for future clinical applications of antibodies against HIV," says Dr. Lutz Gieselmann, physician scientist at the Institute of Virology and first author of the study.

An important special feature of 04_A06 was revealed when analyzing its structure. The antibody has an unusually long amino acid chain that reaches areas of the viral target that are often difficult to access. These areas are highly conserved and likely difficult for the virus to change without losing the ability to function. This may explain why 04_A06 maintains its antiviral properties against CD4bs viral escape variants, which otherwise lead to a loss of function of other antibodies.

In addition to thelaboratory tests, the researchers used computer models to assess the prevention efficacy of 04_A06. The models predicted that a single administration of 04_A06 could offer over 93% protection in clinical applications.

Altogether, the antiviral properties of 04_A06 suggest its use as a promising approach for both treating people living with HIV and preventing infection in those at increased risk. The antibody 04_A06 has been exclusively licensed to Vir Biotechnology, Inc.

More information: Lutz Gieselmann et al, Profiling of HIV-1 elite neutralizer cohort reveals a CD4bs bnAb for HIV-1 prevention and therapy, Nature Immunology (2025). DOI: 10.1038/s41590-025-02286-5 Journal information: Nature Immunology

Provided by University of Cologne