title: Vaccination with lipid core peptides fails to induce epitope-specific T cell responses but confers non-specific protective immunity in a malaria model.
abstract: Vaccines against many pathogens for which conventional approaches have failed remain an unmet public health priority. Synthetic peptide-based vaccines offer an attractive alternative to whole protein and whole organism vaccines, particularly for complex pathogens that cause chronic infection. Previously, we have reported a promising lipid core peptide (LCP) vaccine delivery system that incorporates the antigen, carrier, and adjuvant in a single molecular entity. LCP vaccines have been used to deliver several peptide subunit-based vaccine candidates and induced high titre functional antibodies and protected against Group A streptococcus in mice. Herein, we have evaluated whether LCP constructs incorporating defined CD4(+) and/or CD8(+) T cell epitopes could induce epitope-specific T cell responses and protect against pathogen challenge in a rodent malaria model. We show that LCP vaccines failed to induce an expansion of antigen-specific CD8(+) T cells following primary immunization or by boosting. We further demonstrated that the LCP vaccines induced a non-specific type 2 polarized cytokine response, rather than an epitope-specific canonical CD8(+) T cell type 1 response. Cytotoxic responses of unknown specificity were also induced. These non-specific responses were able to protect against parasite challenge. These data demonstrate that vaccination with lipid core peptides fails to induce canonical epitope-specific T cell responses, at least in our rodent model, but can nonetheless confer non-specific protective immunity against Plasmodium parasite challenge.
authors.affiliation: Infectious Diseases Programme, Queensland Institute of Medical Research, Herston, Queensland, Australia.
authors.forename: Simon H
authors.initials: SH
authors.lastname: Apte
authors.forename: Penny L
authors.initials: PL
authors.lastname: Groves
authors.forename: Mariusz
authors.initials: M
authors.lastname: Skwarczynski
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujita
authors.forename: Chenghung
authors.initials: C
authors.lastname: Chang
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology* / Q000627:therapeutic use; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D022223:Vaccines, Subunit