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.

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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.

Item ID: 56600
Item Type: Article (Refereed Research - C1)
Keywords: malaria, circumsporozoite protein (CSP), self-adjuvanting system, lipopeptide, peptide-based vaccine, cellular immune responses, CD4+ and/or CD8+ T-cell epitopes, INF-γ production
Copyright Information: Copyright © 2016 Doolan & Toth et al; licensee Herbert Publications Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ISSN: 2052-9341
Funders: National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC 496600
Date Deposited: 13 Dec 2018 04:25
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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