Structure-based Vaccines May Protect Against HIV

They studied this protein while it was still embedded in the viral membrane lipid layer by using a combination of nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and surface plasmon resonance (SPR) techniques.

Results published January 10, 2008, in the online issue of the journal Immunity revealed a tilted N-terminal alpha helix connected via a short hinge to a flat C-terminal helical segment. This metastable L-shaped structure was immersed in the viral membrane and was, therefore, less accessible to immune attack. Despite being partially sequestered in the lipid layer a broadly neutralizing antibody (BNAb) called 4E10 was able to extract a buried segment of the protein after the initial encounter with the surface-embedded MPER.

Since the antibody recognizes protein structure, rather than an amino acid sequence, and since this structure is common to HIV-1, HIV-2, and SIV, such recognition has important implications for structure-guided vaccine design.

"The new features of MPER that we have discovered may be useful targets for antibody-based vaccines if they can be held in proper configuration,” explained contributing author Dr. Mikyung Kim, instructor in medicine at the Dana-Farber Cancer Institute. "One way of doing this would be to place them in a synthetic lipid coat on nanoparticles. If the antibodies are not confused by other elements of the virus's protein envelope, this approach may elicit a strong immune response to viral presence.”


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Dana-Farber Cancer Institute