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Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.

Krebs SJ, Kwon YD, Schramm CA, Law WH, Donofrio G, Zhou KH, Gift S, Dussupt V, Georgiev IS, Schätzle S, McDaniel JR, Lai YT, Sastry M, Zhang B, Jarosinski MC, Ransier A, Chenine AL, Asokan M, Bailer RT, Bose M, Cagigi A, Cale EM, Chuang GY, Darko S, Driscoll JI, Druz A, Gorman J, Laboune F, Louder MK, McKee K, Mendez L, Moody MA, O'Sullivan AM, Owen C, Peng D, Rawi R, Sanders-Buell E, Shen CH, Shiakolas AR, Stephens T, Tsybovsky Y, Tucker C, Verardi R, Wang K, Zhou J, Zhou T, Georgiou G, Alam SM, Haynes BF, Rolland M, Matyas GR, Polonis VR, McDermott AB, Douek DC, Shapiro L, Tovanabutra S, Michael NL, Mascola JR, Robb ML, Kwong PD, Doria-Rose NA
Immunity 50 677-691.e13 (2019)
Related entries: 6mto, 6mtp, 6mtr, 6mts, 6mtt

Cited: 53 times
EuropePMC logo PMID: 30876875

Abstract

Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual in the prospective RV217 cohort, we identified three lineages of bNAbs targeting the membrane-proximal external region (MPER) of the HIV-1 envelope. Antibodies RV217-VRC42.01, -VRC43.01, and -VRC46.01 used distinct modes of recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. All three lineages had modest levels of somatic hypermutation and normal antibody-loop lengths and were initiated by the founder virus MPER. The broadest lineage, VRC42, was similar to the known bNAb 4E10. A multimeric immunogen based on the founder MPER activated B cells bearing the unmutated common ancestor of VRC42, with modest maturation of early VRC42 intermediates imparting neutralization breadth. These features suggest that VRC42 may be a promising template for lineage-based vaccine design.

Articles - 6mtq mentioned but not cited (2)

  1. Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual. Krebs SJ, Kwon YD, Schramm CA, Law WH, Donofrio G, Zhou KH, Gift S, Dussupt V, Georgiev IS, Schätzle S, McDaniel JR, Lai YT, Sastry M, Zhang B, Jarosinski MC, Ransier A, Chenine AL, Asokan M, Bailer RT, Bose M, Cagigi A, Cale EM, Chuang GY, Darko S, Driscoll JI, Druz A, Gorman J, Laboune F, Louder MK, McKee K, Mendez L, Moody MA, O'Sullivan AM, Owen C, Peng D, Rawi R, Sanders-Buell E, Shen CH, Shiakolas AR, Stephens T, Tsybovsky Y, Tucker C, Verardi R, Wang K, Zhou J, Zhou T, Georgiou G, Alam SM, Haynes BF, Rolland M, Matyas GR, Polonis VR, McDermott AB, Douek DC, Shapiro L, Tovanabutra S, Michael NL, Mascola JR, Robb ML, Kwong PD, Doria-Rose NA. Immunity 50 677-691.e13 (2019)
  2. N-terminal Transmembrane-Helix Epitope Tag for X-ray Crystallography and Electron Microscopy of Small Membrane Proteins. McIlwain BC, Erwin AL, Davis AR, Ben Koff B, Chang L, Bylund T, Chuang GY, Kwong PD, Ohi MD, Lai YT, Stockbridge RB. J Mol Biol 433 166909 (2021)


Reviews citing this publication (8)

  1. HIV vaccinology: 2021 update. Lee JH, Crotty S. Semin Immunol 51 101470 (2021)
  2. Neutralizing Antibodies Targeting HIV-1 gp41. Caillat C, Guilligay D, Sulbaran G, Weissenhorn W. Viruses 12 E1210 (2020)
  3. Broadly neutralizing antibodies and vaccine design against HIV-1 infection. Wang Q, Zhang L. Front Med 14 30-42 (2020)
  4. A matrix of structure-based designs yields improved VRC01-class antibodies for HIV-1 therapy and prevention. Kwon YD, Asokan M, Gorman J, Zhang B, Liu Q, Louder MK, Lin BC, McKee K, Pegu A, Verardi R, Yang ES, Program VP, Carlton K, Doria-Rose NA, Lusso P, Mascola JR, Kwong PD. MAbs 13 1946918 (2021)
  5. Coevolution of HIV-1 and broadly neutralizing antibodies. Doria-Rose NA, Landais E. Curr Opin HIV AIDS 14 286-293 (2019)
  6. A Structural Update of Neutralizing Epitopes on the HIV Envelope, a Moving Target. Parker Miller E, Finkelstein MT, Erdman MC, Seth PC, Fera D. Viruses 13 1774 (2021)
  7. HIV-1 Entry and Prospects for Protecting against Infection. Bruxelle JF, Trattnig N, Mureithi MW, Landais E, Pantophlet R. Microorganisms 9 228 (2021)
  8. Outsmarting Pathogens with Antibody Engineering. Qerqez AN, Silva RP, Maynard JA. Annu Rev Chem Biomol Eng 14 217-241 (2023)

Articles citing this publication (43)



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