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Karl STEFIC​

Monitoring the sensitivity to broadly neutralizing antibodies of HIV-1 strains transmitted in France

Summary of the presentation : Broadly neutralizing antibodies (bnAbs) are promising agents for prevention and/or treatment of HIV-1 infection. Yet, the huge diversity among HIV-1 envelope (Env) glycoproteins impacts bnAbs potency and breadth across genotypes. Moreover, an increasing resistance to neutralization of HIV-1 over time has been observed. Therefore, sensitivity to bnAbs of all prevalent HIV-1 subtypes needs to be monitored to guide the development of bnAb-based strategies toward clinical use. We assessed the sensitivity to 9 bnAbs against a panel of viruses isolated over a 25-year period of the French epidemic (1987-2012), among the most prevalent subtypes (B and CRF02_AG). Of the bNAbs in clinical development tested here, none neutralized 100% of variants, indicating that combinations will be required to achieve a full coverage. We observed an increased resistance to several bNAbs over the course of the epidemic - especially those targeting the CD4bs – which correlated with the continuous diversification of Env sequences over time.

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