HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds.

Tom L G M van den Kerkhof, Steven W de Taeye, Brigitte D Boeser-Nunnink, Dennis R Burton, Neeltje A Kootstra, Hanneke Schuitemaker, Rogier W Sanders, Marit J van Gils

Journal: Retrovirology 2017;13(1):48

PMID: 27388013

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Abstract

BACKGROUND

Current HIV-1 immunogens are unable to induce antibodies that can neutralize a broad range of HIV-1 (broadly neutralizing antibodies; bNAbs). However, such antibodies are elicited in 10-30 % of HIV-1 infected individuals, and the co-evolution of the virus and the humoral immune responses in these individuals has attracted attention, because they can provide clues for vaccine design.

RESULTS

Here we characterized the NAb responses and envelope glycoprotein evolution in an HIV-1 infected "elite neutralizer" of the Amsterdam Cohort Studies on HIV-1 infection and AIDS who developed an unusually potent bNAb response rapidly after infection. The NAb response was dependent on the N332-glycan and viral resistance against the N332-glycan dependent bNAb PGT135 developed over time but viral escape did not occur at or near this glycan. In contrast, the virus likely escaped by increasing V1 length, with up to 21 amino acids, accompanied by the introduction of 1-3 additional glycans, as well as 2-4 additional cysteine residues within V1.

CONCLUSIONS

In the individual studied here, HIV-1 escaped from N332-glycan directed NAb responses without changing the epitope itself, but by elongating a variable loop that shields this epitope.

Address: Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.; Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.; Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.; Janssen Pharmaceuticals, 2333 CN, Leiden, The Netherlands.; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands. [email protected].; Department of Microbiology and Immunology, Weill Medical College, Cornell University, New York, NY, 10065, USA. [email protected].; Department of Microbiology and Immunology, Weill Medical College, Cornell University, New York, NY, 10065, USA. [email protected].

DOI: 10.1186/s12977-016-0279-4

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MeSH Terms: Antibodies, Neutralizing, Cysteine, Disulfides, HIV Antibodies, HIV-1, Humans, Immune Evasion, Male, Polysaccharides, env Gene Products, Human Immunodeficiency Virus