HIV-1 Env Fusion Peptide Immunogens and Their Use

Millions of people are infected with HIV-1 worldwide, and 2.5 to 3 million new infections have been estimated to occur yearly. Although effective antiretroviral therapies are available, millions succumb to AIDS every year, especially in Sub-Saharan Africa, underscoring the need to develop measures to prevent the spread of this disease.HIV-1 is an enveloped virus, which hides from humoral recognition behind a wide array of protective mechanisms. During infection, the major envelope protein of HIV-1 is cleaved by host cell proteases into two smaller versions (gp120 and gp41). Together gp120 and gp41 make up the HIV-1 Env spike, which is a target for neutralizing antibodies. It is believed that immunization with an effective immunogen based on the HIV-1 Env glycoprotein can elicit a neutralizing response, which may be protective against HIV-1 infection.Researchers at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases used knowledge from the crystal structure of an HIV-1 neutralizing antibody, VRC34.01, in complex with its epitope on the HIV-1 Env trimer, to develop novel immunogens. HIV-1 uses a fusion peptide, located at the N-terminus of the gp41 subunit, to fuse with a target cell to infect the cell. The crystal structure revealed the epitope recognized by VRC34.01 to be composed primarily of the exposed 8 residues of the fusion peptide at the N-terminus of the gp41 subunit. Researchers designed fusion peptide immunogens that were c...
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