Synthetic B-Cell Epitopes Eliciting Cross-Neutralizing Antibodies: Strategies for Future Dengue Vaccine

Babu Ramanathan; Chit Laa Poh; Kristin Kirk; William John Hannan McBride; John Aaskov; Lara Grollo

doi:10.1371/journal.pone.0155900

Synthetic B-Cell Epitopes Eliciting Cross-Neutralizing Antibodies: Strategies for Future Dengue Vaccine

PLoS One. 2016 May 25;11(5):e0155900. doi: 10.1371/journal.pone.0155900. eCollection 2016.

Authors

Babu Ramanathan¹, Chit Laa Poh¹, Kristin Kirk², William John Hannan McBride³, John Aaskov⁴, Lara Grollo⁵

Affiliations

¹ Research Centre for Biomedical Sciences, Sunway University, Kuala Lumpur, Malaysia.
² Swinburne University of Technology, Melbourne, Australia.
³ James Cook University Clinical School, Cairns Base Hospital, Cairns, Queensland, Australia.
⁴ Queensland University of Technology, Brisbane, Queensland, Australia.
⁵ Australian Catholic University, Melbourne, Australia.

Abstract

Dengue virus (DENV) is a major public health threat worldwide. A key element in protection from dengue fever is the neutralising antibody response. Anti-dengue IgG purified from DENV-2 infected human sera showed reactivity against several peptides when evaluated by ELISA and epitope extraction techniques. A multi-step computational approach predicted six antigenic regions within the E protein of DENV-2 that concur with the 6 epitopes identified by the combined ELISA and epitope extraction approach. The selected peptides representing B-cell epitopes were attached to a known dengue T-helper epitope and evaluated for their vaccine potency. Immunization of mice revealed two novel synthetic vaccine constructs that elicited good humoral immune responses and produced cross-reactive neutralising antibodies against DENV-1, 2 and 3. The findings indicate new directions for epitope mapping and contribute towards the future development of multi-epitope based synthetic peptide vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Neutralizing / immunology*
Antibodies, Viral / immunology*
Cross Reactions / immunology
Dengue Vaccines / chemistry
Dengue Vaccines / immunology*
Dengue Virus / chemistry
Dengue Virus / immunology*
Epitopes, B-Lymphocyte / chemistry
Epitopes, B-Lymphocyte / immunology*
Epitopes, T-Lymphocyte / chemistry
Epitopes, T-Lymphocyte / immunology
Humans
Vaccines, Synthetic / chemistry
Vaccines, Synthetic / immunology
Viral Envelope Proteins / chemistry
Viral Envelope Proteins / immunology*

Substances

Antibodies, Neutralizing
Antibodies, Viral
Dengue Vaccines
Epitopes, B-Lymphocyte
Epitopes, T-Lymphocyte
Vaccines, Synthetic
Viral Envelope Proteins

Grants and funding

The work was supported by Swinburne University of Technology: Researcher Development Scheme, Melbourne, Australia, and Grollo Ruzzene Foundation Research Grant. Babu Ramanathan was supported by an International Post-graduate Research Scholarship (IPRS). Support of a Research Fellowship to Babu Ramanathan and funding from internal research grant (INT-VCO-2016-01) from Sunway University, Kuala Lumpur, Malaysia is gratefully acknowledged.