2. Infectious Diseases Programme, Queensland Institute of Medical Research, Herston, QLD 4006, Australia.
3. The University of Queensland, School of Medicine, Herston, QLD 4006, Australia.
4. The University of Queensland, School of Pharmacy, Woolloongabba, QLD 4102, Australia.
5. The University of Queensland, Institute for Molecular Biosciences, St Lucia, QLD 4072, Australia.
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.
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