Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates

Kevin O. Saunders; Nathan I. Nicely; Kevin Wiehe; Mattia Bonsignori; R. Ryan Meyerhoff; Robert Parks; William E. Walkowicz; Baptiste Aussedat; Nelson R. Wu; Fangping Cai; Yusuf Vohra; Peter K. Park; Amanda Eaton; Eden P. Go; Laura L. Sutherland; Richard M. Scearce; Dan H. Barouch; Ruijun Zhang; Tarra Von Holle; R. Glenn Overman; Kara Anasti; Rogier W. Sanders; M. Anthony Moody; Thomas B. Kepler; Bette Korber; Heather Desaire; Sampa Santra; Norman L. Letvin; Gary J. Nabel; David C. Montefiori; Georgia D. Tomaras; Hua-Xin Liao; S. Munir Alam; Samuel J. Danishefsky; Barton F. Haynes

doi:https://doi.org/10.1016/j.celrep.2017.02.003

Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates

Kevin O. Saunders, Nathan I. Nicely, Kevin Wiehe, Mattia Bonsignori, R. Ryan Meyerhoff, Robert Parks, William E. Walkowicz, Baptiste Aussedat, Nelson R. Wu, Fangping Cai, Yusuf Vohra, Peter K. Park, Amanda Eaton, Eden P. Go, Laura L. Sutherland, Richard M. Scearce, Dan H. Barouch, Ruijun Zhang, Tarra Von Holle, R. Glenn OvermanKara Anasti, Rogier W. Sanders, M. Anthony Moody, Thomas B. Kepler, Bette Korber, Heather Desaire, Sampa Santra, Norman L. Letvin, Gary J. Nabel, David C. Montefiori, Georgia D. Tomaras, Hua-Xin Liao, S. Munir Alam, Samuel J. Danishefsky, Barton F. Haynes

Medical Microbiology and Infection Prevention (AMC)

Research output: Contribution to journal › Article › Academic › peer-review

56 Citations (Scopus)

Abstract

Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans-a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors

Original language	English
Pages (from-to)	2175-2188
Journal	Cell reports
Volume	18
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2017.02.003
Publication status	Published - 2017

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https://doi.org/10.1016/j.celrep.2017.02.003

Cite this

Saunders, K. O., Nicely, N. I., Wiehe, K., Bonsignori, M., Meyerhoff, R. R., Parks, R., Walkowicz, W. E., Aussedat, B., Wu, N. R., Cai, F., Vohra, Y., Park, P. K., Eaton, A., Go, E. P., Sutherland, L. L., Scearce, R. M., Barouch, D. H., Zhang, R., Von Holle, T., ... Haynes, B. F. (2017). Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates. Cell reports, 18(9), 2175-2188. https://doi.org/10.1016/j.celrep.2017.02.003

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title = "Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates",

abstract = "Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans-a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors",

author = "Saunders, {Kevin O.} and Nicely, {Nathan I.} and Kevin Wiehe and Mattia Bonsignori and Meyerhoff, {R. Ryan} and Robert Parks and Walkowicz, {William E.} and Baptiste Aussedat and Wu, {Nelson R.} and Fangping Cai and Yusuf Vohra and Park, {Peter K.} and Amanda Eaton and Go, {Eden P.} and Sutherland, {Laura L.} and Scearce, {Richard M.} and Barouch, {Dan H.} and Ruijun Zhang and {Von Holle}, Tarra and Overman, {R. Glenn} and Kara Anasti and Sanders, {Rogier W.} and Moody, {M. Anthony} and Kepler, {Thomas B.} and Bette Korber and Heather Desaire and Sampa Santra and Letvin, {Norman L.} and Nabel, {Gary J.} and Montefiori, {David C.} and Tomaras, {Georgia D.} and Hua-Xin Liao and Alam, {S. Munir} and Danishefsky, {Samuel J.} and Haynes, {Barton F.}",

year = "2017",

doi = "https://doi.org/10.1016/j.celrep.2017.02.003",

language = "English",

volume = "18",

pages = "2175--2188",

journal = "Cell reports",

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Saunders, KO, Nicely, NI, Wiehe, K, Bonsignori, M, Meyerhoff, RR, Parks, R, Walkowicz, WE, Aussedat, B, Wu, NR, Cai, F, Vohra, Y, Park, PK, Eaton, A, Go, EP, Sutherland, LL, Scearce, RM, Barouch, DH, Zhang, R, Von Holle, T, Overman, RG, Anasti, K, Sanders, RW, Moody, MA, Kepler, TB, Korber, B, Desaire, H, Santra, S, Letvin, NL, Nabel, GJ, Montefiori, DC, Tomaras, GD, Liao, H-X, Alam, SM, Danishefsky, SJ & Haynes, BF 2017, 'Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates', Cell reports, vol. 18, no. 9, pp. 2175-2188. https://doi.org/10.1016/j.celrep.2017.02.003

TY - JOUR

T1 - Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates

AU - Saunders, Kevin O.

AU - Nicely, Nathan I.

AU - Wiehe, Kevin

AU - Bonsignori, Mattia

AU - Meyerhoff, R. Ryan

AU - Parks, Robert

AU - Walkowicz, William E.

AU - Aussedat, Baptiste

AU - Wu, Nelson R.

AU - Cai, Fangping

AU - Vohra, Yusuf

AU - Park, Peter K.

AU - Eaton, Amanda

AU - Go, Eden P.

AU - Sutherland, Laura L.

AU - Scearce, Richard M.

AU - Barouch, Dan H.

AU - Zhang, Ruijun

AU - Von Holle, Tarra

AU - Overman, R. Glenn

AU - Anasti, Kara

AU - Sanders, Rogier W.

AU - Moody, M. Anthony

AU - Kepler, Thomas B.

AU - Korber, Bette

AU - Desaire, Heather

AU - Santra, Sampa

AU - Letvin, Norman L.

AU - Nabel, Gary J.

AU - Montefiori, David C.

AU - Tomaras, Georgia D.

AU - Liao, Hua-Xin

AU - Alam, S. Munir

AU - Danishefsky, Samuel J.

AU - Haynes, Barton F.

PY - 2017

Y1 - 2017

N2 - Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans-a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors

AB - Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans-a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors

U2 - https://doi.org/10.1016/j.celrep.2017.02.003

DO - https://doi.org/10.1016/j.celrep.2017.02.003

M3 - Article

C2 - 28249163

SN - 2211-1247

VL - 18

SP - 2175

EP - 2188

JO - Cell reports

JF - Cell reports

IS - 9

ER -