Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology

Amy W. Chung; Manu P. Kumar; Kelly B. Arnold; Wen Han Yu; Matthew K. Schoen; Laura J. Dunphy; Todd J. Suscovich; Nicole Frahm; Caitlyn Linde; Alison E. Mahan; Michelle Hoffner; Hendrik Streeck; Margaret E. Ackerman; M. Juliana McElrath; Hanneke Schuitemaker; Maria G. Pau; Lindsey R. Baden; Jerome H. Kim; Nelson L. Michael; Dan H. Barouch; Douglas A. Lauffenburger; Galit Alter

doi:10.1016/j.cell.2015.10.027

Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology

Amy W. Chung, Manu P. Kumar, Kelly B. Arnold, Wen Han Yu, Matthew K. Schoen, Laura J. Dunphy, Todd J. Suscovich, Nicole Frahm, Caitlyn Linde, Alison E. Mahan, Michelle Hoffner, Hendrik Streeck, Margaret E. Ackerman, M. Juliana McElrath, Hanneke Schuitemaker, Maria G. Pau, Lindsey R. Baden, Jerome H. Kim, Nelson L. Michael, Dan H. BarouchDouglas A. Lauffenburger^*, Galit Alter

^*Corresponding author for this work

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

287 Scopus citations

Abstract

Summary While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine trials. Each vaccine regimen induced a unique humoral "Fc fingerprint." Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive.

Original language	English
Pages (from-to)	988-998
Number of pages	11
Journal	Cell
Volume	163
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2015.10.027
State	Published - 5 Nov 2015
Externally published	Yes

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Chung, A. W., Kumar, M. P., Arnold, K. B., Yu, W. H., Schoen, M. K., Dunphy, L. J., Suscovich, T. J., Frahm, N., Linde, C., Mahan, A. E., Hoffner, M., Streeck, H., Ackerman, M. E., McElrath, M. J., Schuitemaker, H., Pau, M. G., Baden, L. R., Kim, J. H., Michael, N. L., ... Alter, G. (2015). Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology. Cell, 163(4), 988-998. https://doi.org/10.1016/j.cell.2015.10.027

@article{0b1c0abd91dd4d2c9a2581015c7e365e,

title = "Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology",

abstract = "Summary While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine trials. Each vaccine regimen induced a unique humoral {"}Fc fingerprint.{"} Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive.",

author = "Chung, {Amy W.} and Kumar, {Manu P.} and Arnold, {Kelly B.} and Yu, {Wen Han} and Schoen, {Matthew K.} and Dunphy, {Laura J.} and Suscovich, {Todd J.} and Nicole Frahm and Caitlyn Linde and Mahan, {Alison E.} and Michelle Hoffner and Hendrik Streeck and Ackerman, {Margaret E.} and McElrath, {M. Juliana} and Hanneke Schuitemaker and Pau, {Maria G.} and Baden, {Lindsey R.} and Kim, {Jerome H.} and Michael, {Nelson L.} and Barouch, {Dan H.} and Lauffenburger, {Douglas A.} and Galit Alter",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = nov,

day = "5",

doi = "10.1016/j.cell.2015.10.027",

language = "English",

volume = "163",

pages = "988--998",

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Chung, AW, Kumar, MP, Arnold, KB, Yu, WH, Schoen, MK, Dunphy, LJ, Suscovich, TJ, Frahm, N, Linde, C, Mahan, AE, Hoffner, M, Streeck, H, Ackerman, ME, McElrath, MJ, Schuitemaker, H, Pau, MG, Baden, LR, Kim, JH, Michael, NL, Barouch, DH, Lauffenburger, DA & Alter, G 2015, 'Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology', Cell, vol. 163, no. 4, pp. 988-998. https://doi.org/10.1016/j.cell.2015.10.027

TY - JOUR

T1 - Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology

AU - Chung, Amy W.

AU - Kumar, Manu P.

AU - Arnold, Kelly B.

AU - Yu, Wen Han

AU - Schoen, Matthew K.

AU - Dunphy, Laura J.

AU - Suscovich, Todd J.

AU - Frahm, Nicole

AU - Linde, Caitlyn

AU - Mahan, Alison E.

AU - Hoffner, Michelle

AU - Streeck, Hendrik

AU - Ackerman, Margaret E.

AU - McElrath, M. Juliana

AU - Schuitemaker, Hanneke

AU - Pau, Maria G.

AU - Baden, Lindsey R.

AU - Kim, Jerome H.

AU - Michael, Nelson L.

AU - Barouch, Dan H.

AU - Lauffenburger, Douglas A.

AU - Alter, Galit

PY - 2015/11/5

Y1 - 2015/11/5

N2 - Summary While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine trials. Each vaccine regimen induced a unique humoral "Fc fingerprint." Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive.

AB - Summary While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine trials. Each vaccine regimen induced a unique humoral "Fc fingerprint." Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive.

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SN - 0092-8674

VL - 163

SP - 988

EP - 998

JO - Cell

JF - Cell

IS - 4

ER -

Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology

Abstract

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