Poster Presentation 11th Australian Peptide Conference 2015

Lipid core peptide as effective delivery system to trigger cellular immune responses against malaria (#110)

Saranya Chandrudu 1 , Mariusz Skwarczynski 1 , David Pattinson 2 3 , Simon H Apte 2 , Denise L Doolan 2 3 , Istvan Toth 1 4 5
  1. School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia
  2. Infectious Diseases Programme, Queensland Institute of Medical Research, Herston, QLD, Australia
  3. School of Medicine, The University of Queensland, Herston, QLD, Australia
  4. Pharmacy Australia Centre of Excellence, The University of Queensland, Brisbane, QLD, Australia
  5. Institute of Molecular Bioscience, The University of Queensland, St Lucia , QLD, Australia

Malaria, caused by the protozoan parasite Plasmodium, is one of the most prevalent diseases in developing countries. It causes about one million deaths annually. Vaccination against a disease by conventional or traditional methods commonly utilizes live attenuated or killed pathogens. However, disadvantages such as risk of infection, autoimmune responses, allergy development, and manufacturing difficulties have driven the need to develop alternative methods such as fully synthetic peptide-based vaccines. Peptides by themselves are poorly immunogenic; therefore the use of an appropriate immunostimulant is necessary. Lipid Core Peptide (LCP) was found to be a potent vaccine delivery system that is able to induce strong immunity against incorporated epitopes [1]. The aim of this project is to develop an LCP-based vaccine against malaria. 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 [2]. The three vaccine constructs were designed and synthesized, using four different epitopes derived from CSP: P1-SYVPSAEQI (CD8+), P2-SYVPSAEQILEFVKQI (CD4+/CD8+), P3-IYNRNIVNRL (CD8+) and P4-KIYNRNIVNRLLGD (CD4+/CD8+) [3]. LCP constructs incorporating these epitopes were investigated toward induction of epitope-specific cellular immune responses by means of interferon gamma (INF-γ) production. Two leading peptide epitopes (P3 and P4) were identified which upon conjugation to LCP were able to induce high level of INF-γ in mice after subcutaneous immunization. Therefore application of LCP delivery system might be a promising approach towards the development of peptide-based vaccine against malaria. 

  1. Skwarczynski, M.; Zaman.; M. Toth, I. Lipo-peptides/saccharides in peptide vaccine delivery. In Handbook of the Biologically Active Peptides, the 2nd Edition, Abba Kastin (Ed.), Elsevier Inc.: Burlington, Massachusetts, 2013, pp 571-579.
  2. Nardin, E.; Nussenzweig, R., T cell responses to pre-erythrocytic stages of malaria: Role in protection and vaccine development against pre-erythrocytic stages. Annual review of immunology 1993, 11, 687-727.
  3. Apte, S.H.; Groves, P.L.; Skwarczynski, M.; Fujita, Y.; Chang, C.; Toth, I.; Doolan, D.L., Vaccination with lipid core peptides fails to induce epitope-specific t cell responses but confers non-specific protective immunity in a malaria model. PloS one 2012, 7, e40928.