The mechanism of an effective antibody against HIV-1 revealed at the ESRF #WorldAIDSday

01-12-2019

Scientists led by the Institute de Biologie Structurale have used the ESRF to study the structure of an antibody against HIV-1 with promising results. 

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HIV-1 is the most common type of Human Immunodeficiency Virus. It attacks the body's immune system and destroys CD4 cells, which normally help to fight infections. HIV-1 can severely damage the immune system and lead to Acquired Immune Deficiency Syndrome (AIDS). When the virus multiplies, it can mutate into different strains.

The development of an HIV-1 vaccine is the best way to control and eradicate the HIV epidemic. The key to HIV vaccine is the development of the so-called broadly neutralizing antibodies (bnAb). These neutralize multiple HIV-1 viral strains by targeting specific zones of the virus (called epitopes). The discovery of bnAbs in the 90s led to the discovery of an effective treatment against HIV.

Now scientists led by the Institute de Biologie Structurale have studied the structure of a novel highly potent human bnAb called LN01, in complex with its HIV-1 envelope glycoprotein epitope, called gp41 MPER.

The antibody was isolated and characterized by their collaborators at the Institute for Research in Biomedicine in Bellinzona and the Suisse Vaccine Institute in Lausanne, who showed that LN01 is a broad and potent neutralizing antibody that targets 92% of a virus panel made up of 118 different strains, representing the diversity of HIV-1.

The structural studies, carried out on the ESRF beamlines ID30A, ID30B and ID23-1, revealed that the MPER epitope extends into the transmembrane region, which is essential for LN01 to recognize the virus and block its cell entry. "Access to and support at different MX beamlines were essential for efficient selection of suitable crystals and optimal data collection. We especially appreciated the state of the art micro focus beam set-up and automated collection strategies suggested by MxCuBE and ISPyB softwares", explains Christophe Caillat, scientist at the IBS and co-author of the work.

Following their experiments at the ESRF, the team proposed a complete model for interaction of MPER-specific broadly neutralizing antibodies such as LN01, which recognizes the protein epitope as well as lipids present in the virus membrane envelope.

“These are very important results to advance the development of potential vaccine candidates against HIV-1”, explains Winfried Weissenhorn, director of the IBS and corresponding author of the paper.

Reference:

Pinto, D. et al.,  Cell Host and Microbe, Volume 26, Issue 5, 13 November 2019, Pages 623-637.e8. https://doi.org/10.1016/j.chom.2019.09.016

Text by Montserrat Capellas Espuny

Top image: Model of the interaction between LN01 and the MPER epitome. Credits: C. Caillat.