2. Academic Validation
  3. Neutralizing Activity of Broadly Neutralizing anti-HIV-1 Antibodies against Primary African Isolates

Neutralizing Activity of Broadly Neutralizing anti-HIV-1 Antibodies against Primary African Isolates

  • J Virol. 2020 Dec 9;95(5):e01909-20. doi: 10.1128/JVI.01909-20.
Julio C C Lorenzi 1,  Pilar Mendoza 1,  Yehuda Z Cohen 1,  Lilian Nogueira 1,  Christy Lavine 2,  Joseph Sapiente 2,  Marie Wiatr 1,  Nelly R Mugo 3 4,  Andrew Mujugira 5,  Sinead Delany 6,  Jairam Lingappa 4 7 8,  Connie Celum 4 7 9,  Michael S Seaman 2,  Marina Caskey 1,  Michel C Nussenzweig 10 11
Affiliations

Affiliations

  • 1 Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
  • 2 Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
  • 3 Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
  • 4 Department of Global Health, University of Washington, Seattle, Washington, USA.
  • 5 Infectious Diseases Institute, Makerere University, Kampala, Uganda.
  • 6 University of the Witswatersrand, South Africa.
  • 7 Department of Medicine, University of Washington, Seattle, Washington, USA.
  • 8 Department of Pediatrics, University of Washington, Seattle, Washington, USA.
  • 9 Department of Epidemiology, University of Washington, Seattle, Washington, USA.
  • 10 Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA nussen@rockefeller.edu.
  • 11 Howard Hughes Medical Institute.
PMID: 33298542 DOI: 10.1128/JVI.01909-20
Abstract

Novel therapeutic and preventive strategies are needed to contain the HIV-1 epidemic. Broadly neutralizing human Antibodies (bNAbs) with exceptional activity against HIV-1 are currently being tested in HIV-1 prevention trials. The selection of anti-HIV-1 bNAbs for clinical development was primarily guided by their in vitro neutralizing activity against HIV-1 Env pseudotyped viruses. Here we report on the neutralizing activity of 9 anti-HIV-1 bNAbs now in clinical development against 126 Clade A, C, D PBMC-derived primary African isolates. The neutralizing potency and breadth of the bNAbs tested was significantly reduced compared to pseudotyped viruses panels. The difference in sensitivity between pseudotyped viruses and primary isolates varied from 3- to nearly 100-fold depending on the bNAb and the HIV-1 clade. Thus, the neutralizing activity of bNAbs against primary African isolates differs from their activity against pseudovirus panels. The data have significant implications for interpreting the results of ongoing HIV-1 prevention trials.IMPORTANCE HIV remains a major public health problem worldwide, and new therapies and preventive strategies are necessary for controlling the epidemic. Broadly neutralizing Antibodies (bNAbs) have been developed in the past decade to fill this gap. The neutralizing activity of these Antibodies against diverse HIV strains has mostly been measured using Env-pseudotyped viruses, which overestimate bNAb coverage and potency. In this study we measured the neutralizing activity of nine bNAbs against clade A, C, and D HIV isolates derived from cells of African patients living with HIV and produced in peripheral blood mononuclear cells. We found that the coverage and potency of bNAbs were often significantly lower than what was predicted by Env-psuedotyped viruses, and that this decrease was related to the bNAb biding site class. This data is important for the planning and analysis of clinical trials that seek to evaluate bNAbs for the treatment and prevention of HIV Infection in Africa.

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