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  • New CAPRISA antibody identifies a novel vaccine target

    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.
    DOI:10.1371/journal.ppat.1006074.
     

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Centre for the AIDS Programme of Research in South Africa

CAPRISA was created in 2001 and formally established in 2002 under the NIH-funded Comprehensive International Program of Research on AIDS (CIPRA) by five partner institutions; University of KwaZulu-Natal, University of Cape Town, University of Western Cape, National Institute for Communicable Diseases, and Columbia University in New York. CAPRISA is a designated UNAIDS Collaborating Centre for HIV Prevention Research. The main goal of CAPRISA is to undertake globally relevant and locally responsive research that contributes to understanding HIV pathogenesis, prevention and epidemiology as well as the links between tuberculosis and AIDS care.