A preventative HIV vaccine will likely need to generate broadly neutralizing antibodies that are able to recognize diverse viruses from across the globe. Such antibodies have not yet been elicited by vaccination, but develop in some HIVinfected individuals during chronic HIV infection. A better understanding of the regions on the HIV
envelope trimers targeted by broadly neutralizing antibodies may contribute to HIV
vaccine design. In a paper published in PLoS Pathogens, PhD student Kurt Wibmer, who is supervised by Professors Lynn Morris and Penny Moore, described the isolation of an antibody called CAP248-2B, and characterized its epitope using X-ray
crystallography, and negative-stain electron microscopy. This novel epitope spanned both gp120-gp41 interfaces in a manner that is distinct from known HIV antibodies, extending the interface target to include the gp120 C terminus, encircling the base of native pre-fusion trimers.
The study, which is a collaboration between NICD, CAPRISA, the NIH Vaccine Research Center and UCT, also characterized viral escape pathways from the CAP248-2B Ab. Sequence analysis identified unusual mutations in the gp160 cleavage sites that allowed the virus to escape these antibodies. Surprisingly, these mutations made HIV viruses 10-100-fold more sensitive to antibodies targeting another highly conserved epitope, the membraneproximal
external region. Incorporating these mutations into vaccine candidates could
therefore improve the immunogenicity of gp41, and inform HIV immunogen design.
Kurt has recently taken up a postdoctoral fellowship at the Scripps Research
Institute in San Diego, USA.
For more information see:
CK Wibmer, et al. Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape 2017. PLoS Pathogens.
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