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New vaccine-design approach offers hope against HIV and other fast-mutating viruses

Washington: Scientists have unveiled a new technique for vaccine design that could be particularly useful against HIV and other fast-changing viruses.

The researchers demonstrated their new technique by engineering an immunogen, which has promise to reliably initiate an otherwise rare response effective against many types of HIV.

"We`re hoping to test this immunogen soon in mice engineered to produce human antibodies, and eventually in humans," team leader William R. Schief, who is an associate professor of immunology and member of the IAVI Neutralizing Antibody Center at TSRI, said.

Joseph Jardine, a TSRI graduate student in the Schief laboratory, evaluated the genes of VRC01-producing B cells to deduce the identities of the less mature B cells-known as germline B cells-from which they originate.

Germline B cells are the major targets of modern viral vaccines, as it is the initial stimulation of these B cells and their antibodies that leads to a long-term antibody response.

Jardine used a protein modeling software suite called Rosetta to improve the binding of VRC01 germline B cell antibodies to HIV`s envelope protein.

Rosetta identified dozens of mutations that could help improve binding to germline antibodies. Jardine then generated libraries that contained all possible combinations of beneficial mutations, resulting in millions of mutants, and screened them using techniques called yeast surface display and FACS.

This combination of computational prediction and directed evolution successfully produced a few mutant envelope proteins with high affinity for germline VRC01-class antibodies.

Jardine then focused on making a minimal immunogen-much smaller than HIV envelope-and so continued development using the "engineered outer domain (eOD)" previously developed by Po-Ssu Huang in the Schief lab while Schief was at the University of Washington.

Several iterative rounds of design and selection using a panel of germline antibodies produced a final, optimized immunogen-a construct they called eOD-GT6.

The research has been published in Science Express the online edition of the journal Science.