In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection

Ruklanthi de Alwis, Martina Beltramello, William Messer, Soila Sukupolvi-Petty, Wahala M P B Wahala, Annette Kraus, Nicholas P. Olivarez, Quang Pham, James Brian, Wen Yang Tsai, Wei Kung Wang, Scott Halstead, Srisakul Kliks, Michael S. Diamond, Ralph Baric, Antonio Lanzavecchia, Federica Sallusto, Aravinda M. de Silva

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization.

Original languageEnglish (US)
Article numbere1188
JournalPLoS Neglected Tropical Diseases
Volume5
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

Fingerprint

Dengue Virus
Virus Diseases
Antibody Formation
Antibodies
Viral Matrix Proteins
Antibody Binding Sites
Viral Envelope Proteins
Heterophile Antibodies
Viruses
Dengue
Fc Receptors
Infection
Virion
B-Lymphocytes
Monoclonal Antibodies
Antigens
Serogroup
Serum

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

de Alwis, R., Beltramello, M., Messer, W., Sukupolvi-Petty, S., Wahala, W. M. P. B., Kraus, A., ... de Silva, A. M. (2011). In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection. PLoS Neglected Tropical Diseases, 5(6), [e1188]. https://doi.org/10.1371/journal.pntd.0001188

In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection. / de Alwis, Ruklanthi; Beltramello, Martina; Messer, William; Sukupolvi-Petty, Soila; Wahala, Wahala M P B; Kraus, Annette; Olivarez, Nicholas P.; Pham, Quang; Brian, James; Tsai, Wen Yang; Wang, Wei Kung; Halstead, Scott; Kliks, Srisakul; Diamond, Michael S.; Baric, Ralph; Lanzavecchia, Antonio; Sallusto, Federica; de Silva, Aravinda M.

In: PLoS Neglected Tropical Diseases, Vol. 5, No. 6, e1188, 06.2011.

Research output: Contribution to journalArticle

de Alwis, R, Beltramello, M, Messer, W, Sukupolvi-Petty, S, Wahala, WMPB, Kraus, A, Olivarez, NP, Pham, Q, Brian, J, Tsai, WY, Wang, WK, Halstead, S, Kliks, S, Diamond, MS, Baric, R, Lanzavecchia, A, Sallusto, F & de Silva, AM 2011, 'In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection', PLoS Neglected Tropical Diseases, vol. 5, no. 6, e1188. https://doi.org/10.1371/journal.pntd.0001188
de Alwis, Ruklanthi ; Beltramello, Martina ; Messer, William ; Sukupolvi-Petty, Soila ; Wahala, Wahala M P B ; Kraus, Annette ; Olivarez, Nicholas P. ; Pham, Quang ; Brian, James ; Tsai, Wen Yang ; Wang, Wei Kung ; Halstead, Scott ; Kliks, Srisakul ; Diamond, Michael S. ; Baric, Ralph ; Lanzavecchia, Antonio ; Sallusto, Federica ; de Silva, Aravinda M. / In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection. In: PLoS Neglected Tropical Diseases. 2011 ; Vol. 5, No. 6.
@article{c3efc04c4050416ea6453ff90491e7fc,
title = "In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection",
abstract = "Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization.",
author = "{de Alwis}, Ruklanthi and Martina Beltramello and William Messer and Soila Sukupolvi-Petty and Wahala, {Wahala M P B} and Annette Kraus and Olivarez, {Nicholas P.} and Quang Pham and James Brian and Tsai, {Wen Yang} and Wang, {Wei Kung} and Scott Halstead and Srisakul Kliks and Diamond, {Michael S.} and Ralph Baric and Antonio Lanzavecchia and Federica Sallusto and {de Silva}, {Aravinda M.}",
year = "2011",
month = "6",
doi = "10.1371/journal.pntd.0001188",
language = "English (US)",
volume = "5",
journal = "PLoS Neglected Tropical Diseases",
issn = "1935-2727",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection

AU - de Alwis, Ruklanthi

AU - Beltramello, Martina

AU - Messer, William

AU - Sukupolvi-Petty, Soila

AU - Wahala, Wahala M P B

AU - Kraus, Annette

AU - Olivarez, Nicholas P.

AU - Pham, Quang

AU - Brian, James

AU - Tsai, Wen Yang

AU - Wang, Wei Kung

AU - Halstead, Scott

AU - Kliks, Srisakul

AU - Diamond, Michael S.

AU - Baric, Ralph

AU - Lanzavecchia, Antonio

AU - Sallusto, Federica

AU - de Silva, Aravinda M.

PY - 2011/6

Y1 - 2011/6

N2 - Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization.

AB - Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization.

UR - http://www.scopus.com/inward/record.url?scp=79959856684&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959856684&partnerID=8YFLogxK

U2 - 10.1371/journal.pntd.0001188

DO - 10.1371/journal.pntd.0001188

M3 - Article

C2 - 21713020

AN - SCOPUS:79959856684

VL - 5

JO - PLoS Neglected Tropical Diseases

JF - PLoS Neglected Tropical Diseases

SN - 1935-2727

IS - 6

M1 - e1188

ER -