Cell News—How a rare class of antibodies neutralizes the HIV-1 virus

Scanning electron micrograph of HIV particles infecting a human T cell. Image from National Institute of Allergy and Infectious Diseases

Scanning electron micrograph of HIV particles infecting a human T cell. Image from National Institute of Allergy and Infectious Diseases

The Holy Grail in the search for an HIV-1 vaccine is the “broadly neutralizing antibody” or bNAb. The target for all immune antibodies attacking HIV-1 is the virus’s glycoprotein envelope (Env), which is a complicated twist of two proteins, gp120 and gp41. The resulting Env is a powerful shape shifter through mutation and a master at protecting its essential molecules from detection. Most patients infected with HIV-1 develop antibodies against only a few strains of HIV-1 and fail to outrun the rapidly mutating virus. But a tiny percentage of HIV-1 patients manage to hold their own by developing bNAbs over time. Isolated from these extremely rare patients, the VRC01 class of bNAbs has been effective in animal experiments and in preliminary human trials against HIV-1.

 

Louise Scharf in the California Institute of Technology (Caltech) lab of ASCB member Pamela Bjorkman along with colleagues at Caltech, the Fred Hutchinson Cancer Research Center, and Rockefeller University took a much closer look at how an antibody of the VRC01 class interacted with the HIV-1 Env molecule, gp120. The researchers used X-ray crystallography to resolve at the atomic level the exact shape of a VRC01 bNAb on its own and when interacting with the pg120 Env molecule. In a new paper in eLife, they report that unlike most antibodies, which mature by changing shape as they come in contact with a target immunogen, the VRC01 antibody retained its “immature” form, growing instead more positively charged and strengthening its grip on gp120. The Caltech researchers believe that this makes gp120 an immunogen candidate for an HIV-1 vaccine. Molecularly remodeled into a form that would prime antibodies into forming a VRC01 class shape, the new gp120 could be the trigger for a broad neutralizing immune reaction against HIV-1.

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