The Humor Immunology Unit of the Pasteur Institute discovered powerful neutralizing antibodies against the hepatitis E (VHE) virus. They could be used in prevention or treatment against these infections which affect around 20 million people worldwide each year. Structural analyzes, carried out with the nanoimagery platform, have made it possible to see atomic the neutralizing site recognized by these antibodies. These results constitute a basis for the rational design of vaccines and immunotherapy against the VHE.
The hepatitis E virus infection (VHE) represents the main cause of acute hepatitis, affecting approximately 20 million people worldwide and leading to 30,000 to 40,000 deaths. If the VHE infection is most often benign, it can nevertheless evolve towards serious forms, in particular an acute potential hepatic insufficiency in pregnant women, as well as chronic hepatitis in immunode -depressed people.
The antibodies directed against the capside protein located on the surface of the virus play an essential role for control and protection against infection, but their properties remain largely overlooked. To date, no specific antiviral treatment against acute vhe infection is available and, although there is an effective vaccine to prevent infection, it is only approved in China and its use is mainly recommended in response to epidemics.
In the study by the humoral immunology unit, led by Hugo Mouquet, the researchers have carried out a detailed characterization of more than a hundred human monoclonal antibodies specific to the Capside Protein (CA) of the VHE, which they produced from the B lymphocytes Memoirs of individuals in remission after exposure to the virus. The majority of these antibodies recognize the different variants of the VHE and also interact the Rat hepatitis E virus, an important zoonotic threat to humans.
Among these various antibodies, scientists have identified powerful neutralizing antibodies that interact with the P (Protoding or protuberant) domain of the CA protein. They carried out structural analyzes by cryo-electronic microscopy of CA protein in complex with three of these broad spectrum neutralizing antibodies. These analyzes, carried out in collaboration with Eduard Baquero Salazar of the Nanoimagerie platform, made it possible to identify atomic the neutralizing site recognized by these antibodies, located on two loops of the P for Apex of the Viral Spicule.
These results provide precious light on the protective humoral response against the VHE and offer a solid base for the rational design of vaccines and immunotherapy against the VHE. Indeed, these neutralizing antibodies represent promising candidates for prophylactic and/or therapeutic interventions against VHE infections. More particularly, versions with a half-life lying by engineering antibodies thus extending their duration of action, could provide protective immunity to immunocompromised populations and pregnant women.
This work was published in May 2025 in the journal Science Advances.
References:
Structural Basis for hepatitis and virus neutralization by Poten Human Antibodies. Luis M. Molinos-Albert, Eduard Baquero, Cyril Planchais, Virginie doceul, Hicham El Costa, Estelle Mottez, Vincent Mallet, Stanislas Pol, Matthew L. Albert, Nicole Pavio, Cécile Alanio, Jordan D. Dimitrov, Hugo Mouquet. Ski Adv. 2025 May 9; 11 (19): Eadu8811. DOI: 10.1126/Wandererv.adu8811. Epub 2025 May 7. PMID: 40333967