Synthesis and immunological evaluation of peptide-based vaccine candidates against malaria

Chandrudu, Saranya, Skwarczynski, Mariusz, Pattinson, David, Apte, Simon H., Doolan, Denise L. and Toth, Istvan (2016) Synthesis and immunological evaluation of peptide-based vaccine candidates against malaria. Biochemical Compounds, 4 1: . doi:10.7243/2052-9341-4-1


Author Chandrudu, Saranya
Skwarczynski, Mariusz
Pattinson, David
Apte, Simon H.
Doolan, Denise L.
Toth, Istvan
Title Synthesis and immunological evaluation of peptide-based vaccine candidates against malaria
Journal name Biochemical Compounds
ISSN 2052-9341
Publication date 2016
Sub-type Article (original research)
DOI 10.7243/2052-9341-4-1
Open Access Status DOI
Volume 4
Issue 1
Total pages 6
Place of publication Bedfordshire, United Kingdom
Publisher Herbert Publications
Collection year 2017
Language eng
Formatted abstract
Background: Malaria, caused by the protozoan parasite Plasmodium, is one of the main causes of morbidity and mortality of the whole human population.Intensive, ongoing research aims to develop an effective vaccine against malaria; however, it has been unsuccessful for over a century. The circumsporozoite protein (CSP) plays crucial a role in the parasite life cycle. CSP is the most dominant surface antigen of the initial pre-erythrocytic stage. We designed vaccine constructs using four different CD4+ and CD8+ T cell epitopes derived from the CSP and used the lipid core peptide (LCP) as a self-adjuvanting delivery system.

Methods: All the constructs were synthesized using microwave-assisted solid phase peptide synthesis (SPPS). Immunological evaluation was carried out following subcutaneous administration of LCP-based vaccine candidates in a BALB/c mouse model. Interferon gamma (IFN-γ) production was used to measure the induction of epitope-specific cellular immune responses after vaccination.

Results:
Self-adjuvanting LCP malaria vaccines composed of different epitopes were synthesized.To determine whether the vaccine candidates were able to induce cellular immunity, mice were immunized with LCP constructs or peptide epitopes adjuvanted with cholera toxin.Two of the tested constructs induced a high level of INF-γ in mice after subcutaneous immunization.

Conclusions: We have demonstrated here for the first time that the LCP delivery system induced epitopespecific cellular immune responses against an antigen derived from Plasmodium.
Keyword Malaria
Circumsporozoite protein (CSP)
Self-adjuvanting system
Lipopeptide
Peptide-based vaccine
Cellular immune responses
CD4+ and/or CD8+ T-cell epitopes
INF-γ production
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Mon, 22 Feb 2016, 14:11:16 EST by Dr Mariusz Skwarczynski on behalf of School of Chemistry & Molecular Biosciences