Structure-based Vaccines May Protect Against HIV

Molecular virologists have used sophisticated imaging systems to study a membrane protein common to most strains of HIV-1 with the intent of exploiting this protein for future vaccine development.

Investigators from the Dana-Farber Cancer Institute (Boston, MA, USA) focused their attention on the viral membrane protein gp41 with specific interest in the membrane proximal ectodomain region (MPER), which is common among most HIV-I strains. 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