Advanced search
1 file | 1.87 MB Add to list

A monoclonal antibody-based immunoassay to measure the antibody response against the repeat region of the circumsporozoite protein of Plasmodium falciparum

(2016) MALARIA JOURNAL. 15(1).
Author
Organization
Abstract
Background: The malaria vaccine candidate RTS, S/AS01 (GSK Vaccines) induces high IgG concentration against the circumsporozoite protein (CSP) of Plasmodium falciparum. In human vaccine recipients circulating anti-CSP antibody concentrations are associated with protection against infection but appear not to be the correlate of protection. However, in a humanized mouse model of malaria infection prophylactic administration of a human monoclonal antibody (MAL1C), derived from a RTS, S/AS01-immunized volunteer, directed against the CSP repeat region, conveyed full protection in a dose-dependent manner suggesting that antibodies alone are able to prevent P. falciparum infection when present in sufficiently high concentrations. A competition ELISA was developed to measure the presence of MAL1C-like antibodies in polyclonal sera from RTS, S/AS01 vaccine recipients and study their possible contribution to protection against infection. Results: MAL1C-like antibodies present in polyclonal vaccine-induced sera were evaluated for their ability to compete with biotinylated monoclonal antibody MAL1C for binding sites on the capture antigen consisting of the recombinant protein encompassing 32 NANP repeats of CSP (R32LR). Serum samples were taken at different time points from participants in two RTS, S/AS01 vaccine studies (NCT01366534 and NCT01857869). Vaccine-induced protection status of the study participants was determined based on the outcome of experimental challenge with infected mosquito bites after vaccination. Optimal conditions were established to reliably detect MAL1C-like antibodies in polyclonal sera. Polyclonal anti-CSP antibodies and MAL1C-like antibody content were measured in 276 serum samples from RTS, S/AS01 vaccine recipients using the standard ELISA and MAL-1C competition ELISA, respectively. A strong correlation was observed between the results from these assays. However, no correlation was found between the results of either assay and protection against infection. Conclusions: The competition ELISA to measure MAL1C-like antibodies in polyclonal sera from RTS, S/AS01 vaccine recipients was robust and reliable but did not reveal the elusive correlate of protection.
Keywords
Malaria, Competition ELISA, Enzyme-linked immunosorbent assay, Immunoassay, Circumsporozoite protein, CANDIDATE MALARIA VACCINE, DOUBLE-BLIND, IMMUNE-RESPONSE, NAIVE ADULTS, EFFICACY, SAFETY, TRIAL, IMMUNOGENICITY, IMMUNIZATION, INFECTION

Downloads

  • 12936 2016 Article 1596.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 1.87 MB

Citation

Please use this url to cite or link to this publication:

MLA
Radin, Kristina, Frédéric Clement, Erik Jongert, et al. “A Monoclonal Antibody-based Immunoassay to Measure the Antibody Response Against the Repeat Region of the Circumsporozoite Protein of Plasmodium Falciparum.” MALARIA JOURNAL 15.1 (2016): n. pag. Print.
APA
Radin, K., Clement, F., Jongert, E., Sterckx, Y. G., Ockenhouse, C., Regules, J., Lemiale, F., et al. (2016). A monoclonal antibody-based immunoassay to measure the antibody response against the repeat region of the circumsporozoite protein of Plasmodium falciparum. MALARIA JOURNAL, 15(1).
Chicago author-date
Radin, Kristina, Frédéric Clement, Erik Jongert, Yann GJ Sterckx, Christian Ockenhouse, Jason Regules, Franck Lemiale, and Geert Leroux-Roels. 2016. “A Monoclonal Antibody-based Immunoassay to Measure the Antibody Response Against the Repeat Region of the Circumsporozoite Protein of Plasmodium Falciparum.” Malaria Journal 15 (1).
Chicago author-date (all authors)
Radin, Kristina, Frédéric Clement, Erik Jongert, Yann GJ Sterckx, Christian Ockenhouse, Jason Regules, Franck Lemiale, and Geert Leroux-Roels. 2016. “A Monoclonal Antibody-based Immunoassay to Measure the Antibody Response Against the Repeat Region of the Circumsporozoite Protein of Plasmodium Falciparum.” Malaria Journal 15 (1).
Vancouver
1.
Radin K, Clement F, Jongert E, Sterckx YG, Ockenhouse C, Regules J, et al. A monoclonal antibody-based immunoassay to measure the antibody response against the repeat region of the circumsporozoite protein of Plasmodium falciparum. MALARIA JOURNAL. 2016;15(1).
IEEE
[1]
K. Radin et al., “A monoclonal antibody-based immunoassay to measure the antibody response against the repeat region of the circumsporozoite protein of Plasmodium falciparum,” MALARIA JOURNAL, vol. 15, no. 1, 2016.
@article{8528343,
  abstract     = {Background: The malaria vaccine candidate RTS, S/AS01 (GSK Vaccines) induces high IgG concentration against the circumsporozoite protein (CSP) of Plasmodium falciparum. In human vaccine recipients circulating anti-CSP antibody concentrations are associated with protection against infection but appear not to be the correlate of protection. However, in a humanized mouse model of malaria infection prophylactic administration of a human monoclonal antibody (MAL1C), derived from a RTS, S/AS01-immunized volunteer, directed against the CSP repeat region, conveyed full protection in a dose-dependent manner suggesting that antibodies alone are able to prevent P. falciparum infection when present in sufficiently high concentrations. A competition ELISA was developed to measure the presence of MAL1C-like antibodies in polyclonal sera from RTS, S/AS01 vaccine recipients and study their possible contribution to protection against infection. 
Results: MAL1C-like antibodies present in polyclonal vaccine-induced sera were evaluated for their ability to compete with biotinylated monoclonal antibody MAL1C for binding sites on the capture antigen consisting of the recombinant protein encompassing 32 NANP repeats of CSP (R32LR). Serum samples were taken at different time points from participants in two RTS, S/AS01 vaccine studies (NCT01366534 and NCT01857869). Vaccine-induced protection status of the study participants was determined based on the outcome of experimental challenge with infected mosquito bites after vaccination. Optimal conditions were established to reliably detect MAL1C-like antibodies in polyclonal sera. Polyclonal anti-CSP antibodies and MAL1C-like antibody content were measured in 276 serum samples from RTS, S/AS01 vaccine recipients using the standard ELISA and MAL-1C competition ELISA, respectively. A strong correlation was observed between the results from these assays. However, no correlation was found between the results of either assay and protection against infection. 
Conclusions: The competition ELISA to measure MAL1C-like antibodies in polyclonal sera from RTS, S/AS01 vaccine recipients was robust and reliable but did not reveal the elusive correlate of protection.},
  articleno    = {543},
  author       = {Radin, Kristina and Clement, Frédéric and Jongert, Erik and Sterckx, Yann GJ and Ockenhouse, Christian and Regules, Jason and Lemiale, Franck and Leroux-Roels, Geert},
  issn         = {1475-2875},
  journal      = {MALARIA JOURNAL},
  keywords     = {Malaria,Competition ELISA,Enzyme-linked immunosorbent assay,Immunoassay,Circumsporozoite protein,CANDIDATE MALARIA VACCINE,DOUBLE-BLIND,IMMUNE-RESPONSE,NAIVE ADULTS,EFFICACY,SAFETY,TRIAL,IMMUNOGENICITY,IMMUNIZATION,INFECTION},
  language     = {eng},
  number       = {1},
  pages        = {11},
  title        = {A monoclonal antibody-based immunoassay to measure the antibody response against the repeat region of the circumsporozoite protein of Plasmodium falciparum},
  url          = {http://dx.doi.org/10.1186/s12936-016-1596-8},
  volume       = {15},
  year         = {2016},
}

Altmetric
View in Altmetric
Web of Science
Times cited: