A novel virus-like particle based vaccine platform displaying the placental malaria antigen VAR2CSA

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

A novel virus-like particle based vaccine platform displaying the placental malaria antigen VAR2CSA. / Thrane, Susan; Janitzek, Christoph M; Agerbæk, Mette Ø; Ditlev, Sisse B; dos Santos Marques Resende, Mafalda; Nielsen, Morten A; Theander, Thor G; Salanti, Ali; Pedersen, Adam Frederik Sander.

In: PloS one, Vol. 10, No. 11, e0143071, 2015.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Thrane, S, Janitzek, CM, Agerbæk, MØ, Ditlev, SB, dos Santos Marques Resende, M, Nielsen, MA, Theander, TG, Salanti, A & Pedersen, AFS 2015, 'A novel virus-like particle based vaccine platform displaying the placental malaria antigen VAR2CSA', PloS one, vol. 10, no. 11, e0143071. https://doi.org/10.1371/journal.pone.0143071

APA

Thrane, S., Janitzek, C. M., Agerbæk, M. Ø., Ditlev, S. B., dos Santos Marques Resende, M., Nielsen, M. A., Theander, T. G., Salanti, A., & Pedersen, A. F. S. (2015). A novel virus-like particle based vaccine platform displaying the placental malaria antigen VAR2CSA. PloS one, 10(11), [e0143071]. https://doi.org/10.1371/journal.pone.0143071

Vancouver

Thrane S, Janitzek CM, Agerbæk MØ, Ditlev SB, dos Santos Marques Resende M, Nielsen MA et al. A novel virus-like particle based vaccine platform displaying the placental malaria antigen VAR2CSA. PloS one. 2015;10(11). e0143071. https://doi.org/10.1371/journal.pone.0143071

Author

Thrane, Susan ; Janitzek, Christoph M ; Agerbæk, Mette Ø ; Ditlev, Sisse B ; dos Santos Marques Resende, Mafalda ; Nielsen, Morten A ; Theander, Thor G ; Salanti, Ali ; Pedersen, Adam Frederik Sander. / A novel virus-like particle based vaccine platform displaying the placental malaria antigen VAR2CSA. In: PloS one. 2015 ; Vol. 10, No. 11.

Bibtex

@article{948769a490774651a2e0ea182aa7312e,
title = "A novel virus-like particle based vaccine platform displaying the placental malaria antigen VAR2CSA",
abstract = "Placental malaria caused by Plasmodium falciparum is a major cause of mortality and severe morbidity. Clinical testing of a soluble protein-based vaccine containing the parasite ligand, VAR2CSA, has been initiated. VAR2CSA binds to the human receptor chondroitin sulphate A (CSA) and is responsible for sequestration of Plasmodium falciparum infected erythrocytes in the placenta. It is imperative that a vaccine against malaria in pregnancy, if administered to women before they become pregnant, can induce a strong and long lasting immune response. While most soluble protein-based vaccines have failed during clinical testing, virus-like particle (VLP) based vaccines (e.g., the licensed human papillomavirus vaccines) have demonstrated high efficacy, suggesting that the spatial assembly of the vaccine antigen is a critical parameter for inducing an optimal long-lasting protective immune response. We have developed a VLP vaccine display platform by identifying regions of the HPV16 L1 coat protein where a biotin acceptor site (AviTagTM) can be inserted without compromising VLP-assembly. Subsequent biotinylation of Avi-L1 VLPs allow us to anchor monovalent streptavidin (mSA)-fused proteins to the biotin, thereby obtaining a dense and repetitive VLP-display of the vaccine antigen. The mSA-VAR2CSA antigen was delivered on the Avi-L1 VLP platform and tested in C57BL/6 mice in comparison to two soluble protein-based vaccines consisting of naked VAR2CSA and mSA-VAR2CSA. The mSA-VAR2CSA Avi-L1 VLP and soluble mSA-VAR2CSA vaccines induced higher antibody titers than the soluble naked VAR2CSA vaccine after three immunizations. The VAR2CSA Avi-L1 VLP vaccine induced statistically significantly higher endpoint titres compared to the soluble mSA-VAR2CSA vaccine, after 1st and 2nd immunization; however, this difference was not statistically significant after 3rd immunization. Importantly, the VLP-VAR2CSA induced antibodies were functional in inhibiting the binding of parasites to CSA. This study demonstrates that the described Avi-L1 VLP-platform may serve as a versatile system for facilitating optimal VLP-display of large and complex vaccine antigens.",
author = "Susan Thrane and Janitzek, {Christoph M} and Agerb{\ae}k, {Mette {\O}} and Ditlev, {Sisse B} and {dos Santos Marques Resende}, Mafalda and Nielsen, {Morten A} and Theander, {Thor G} and Ali Salanti and Pedersen, {Adam Frederik Sander}",
year = "2015",
doi = "10.1371/journal.pone.0143071",
language = "English",
volume = "10",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

RIS

TY - JOUR

T1 - A novel virus-like particle based vaccine platform displaying the placental malaria antigen VAR2CSA

AU - Thrane, Susan

AU - Janitzek, Christoph M

AU - Agerbæk, Mette Ø

AU - Ditlev, Sisse B

AU - dos Santos Marques Resende, Mafalda

AU - Nielsen, Morten A

AU - Theander, Thor G

AU - Salanti, Ali

AU - Pedersen, Adam Frederik Sander

PY - 2015

Y1 - 2015

N2 - Placental malaria caused by Plasmodium falciparum is a major cause of mortality and severe morbidity. Clinical testing of a soluble protein-based vaccine containing the parasite ligand, VAR2CSA, has been initiated. VAR2CSA binds to the human receptor chondroitin sulphate A (CSA) and is responsible for sequestration of Plasmodium falciparum infected erythrocytes in the placenta. It is imperative that a vaccine against malaria in pregnancy, if administered to women before they become pregnant, can induce a strong and long lasting immune response. While most soluble protein-based vaccines have failed during clinical testing, virus-like particle (VLP) based vaccines (e.g., the licensed human papillomavirus vaccines) have demonstrated high efficacy, suggesting that the spatial assembly of the vaccine antigen is a critical parameter for inducing an optimal long-lasting protective immune response. We have developed a VLP vaccine display platform by identifying regions of the HPV16 L1 coat protein where a biotin acceptor site (AviTagTM) can be inserted without compromising VLP-assembly. Subsequent biotinylation of Avi-L1 VLPs allow us to anchor monovalent streptavidin (mSA)-fused proteins to the biotin, thereby obtaining a dense and repetitive VLP-display of the vaccine antigen. The mSA-VAR2CSA antigen was delivered on the Avi-L1 VLP platform and tested in C57BL/6 mice in comparison to two soluble protein-based vaccines consisting of naked VAR2CSA and mSA-VAR2CSA. The mSA-VAR2CSA Avi-L1 VLP and soluble mSA-VAR2CSA vaccines induced higher antibody titers than the soluble naked VAR2CSA vaccine after three immunizations. The VAR2CSA Avi-L1 VLP vaccine induced statistically significantly higher endpoint titres compared to the soluble mSA-VAR2CSA vaccine, after 1st and 2nd immunization; however, this difference was not statistically significant after 3rd immunization. Importantly, the VLP-VAR2CSA induced antibodies were functional in inhibiting the binding of parasites to CSA. This study demonstrates that the described Avi-L1 VLP-platform may serve as a versatile system for facilitating optimal VLP-display of large and complex vaccine antigens.

AB - Placental malaria caused by Plasmodium falciparum is a major cause of mortality and severe morbidity. Clinical testing of a soluble protein-based vaccine containing the parasite ligand, VAR2CSA, has been initiated. VAR2CSA binds to the human receptor chondroitin sulphate A (CSA) and is responsible for sequestration of Plasmodium falciparum infected erythrocytes in the placenta. It is imperative that a vaccine against malaria in pregnancy, if administered to women before they become pregnant, can induce a strong and long lasting immune response. While most soluble protein-based vaccines have failed during clinical testing, virus-like particle (VLP) based vaccines (e.g., the licensed human papillomavirus vaccines) have demonstrated high efficacy, suggesting that the spatial assembly of the vaccine antigen is a critical parameter for inducing an optimal long-lasting protective immune response. We have developed a VLP vaccine display platform by identifying regions of the HPV16 L1 coat protein where a biotin acceptor site (AviTagTM) can be inserted without compromising VLP-assembly. Subsequent biotinylation of Avi-L1 VLPs allow us to anchor monovalent streptavidin (mSA)-fused proteins to the biotin, thereby obtaining a dense and repetitive VLP-display of the vaccine antigen. The mSA-VAR2CSA antigen was delivered on the Avi-L1 VLP platform and tested in C57BL/6 mice in comparison to two soluble protein-based vaccines consisting of naked VAR2CSA and mSA-VAR2CSA. The mSA-VAR2CSA Avi-L1 VLP and soluble mSA-VAR2CSA vaccines induced higher antibody titers than the soluble naked VAR2CSA vaccine after three immunizations. The VAR2CSA Avi-L1 VLP vaccine induced statistically significantly higher endpoint titres compared to the soluble mSA-VAR2CSA vaccine, after 1st and 2nd immunization; however, this difference was not statistically significant after 3rd immunization. Importantly, the VLP-VAR2CSA induced antibodies were functional in inhibiting the binding of parasites to CSA. This study demonstrates that the described Avi-L1 VLP-platform may serve as a versatile system for facilitating optimal VLP-display of large and complex vaccine antigens.

U2 - 10.1371/journal.pone.0143071

DO - 10.1371/journal.pone.0143071

M3 - Journal article

C2 - 26599509

VL - 10

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 11

M1 - e0143071

ER -

ID: 148687154