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Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies.

Publication ,  Journal Article
Bonsignori, M; Kreider, EF; Fera, D; Meyerhoff, RR; Bradley, T; Wiehe, K; Alam, SM; Aussedat, B; Walkowicz, WE; Hwang, K-K; Saunders, KO ...
Published in: Sci Transl Med
March 15, 2017

A preventive HIV-1 vaccine should induce HIV-1-specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3-glycan bnAb. Two autologous neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3-glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs.

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Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

March 15, 2017

Volume

9

Issue

381

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Protein Binding
  • Polysaccharides
  • Phylogeny
  • Neutralization Tests
  • Mutation
  • Male
  • Humans
  • HIV-1
  • Crystallography, X-Ray
 

Citation

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Bonsignori, M., Kreider, E. F., Fera, D., Meyerhoff, R. R., Bradley, T., Wiehe, K., … Haynes, B. F. (2017). Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies. Sci Transl Med, 9(381). https://doi.org/10.1126/scitranslmed.aai7514
Bonsignori, Mattia, Edward F. Kreider, Daniela Fera, R Ryan Meyerhoff, Todd Bradley, Kevin Wiehe, S Munir Alam, et al. “Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies.Sci Transl Med 9, no. 381 (March 15, 2017). https://doi.org/10.1126/scitranslmed.aai7514.
Bonsignori M, Kreider EF, Fera D, Meyerhoff RR, Bradley T, Wiehe K, et al. Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies. Sci Transl Med. 2017 Mar 15;9(381).
Bonsignori, Mattia, et al. “Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies.Sci Transl Med, vol. 9, no. 381, Mar. 2017. Pubmed, doi:10.1126/scitranslmed.aai7514.
Bonsignori M, Kreider EF, Fera D, Meyerhoff RR, Bradley T, Wiehe K, Alam SM, Aussedat B, Walkowicz WE, Hwang K-K, Saunders KO, Zhang R, Gladden MA, Monroe A, Kumar A, Xia S-M, Cooper M, Louder MK, McKee K, Bailer RT, Pier BW, Jette CA, Kelsoe G, Williams WB, Morris L, Kappes J, Wagh K, Kamanga G, Cohen MS, Hraber PT, Montefiori DC, Trama A, Liao H-X, Kepler TB, Moody MA, Gao F, Danishefsky SJ, Mascola JR, Shaw GM, Hahn BH, Harrison SC, Korber BT, Haynes BF. Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies. Sci Transl Med. 2017 Mar 15;9(381).

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

March 15, 2017

Volume

9

Issue

381

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Protein Binding
  • Polysaccharides
  • Phylogeny
  • Neutralization Tests
  • Mutation
  • Male
  • Humans
  • HIV-1
  • Crystallography, X-Ray