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(8):e40928. doi: 10.1371/journal.pone.0040928. Epub 2012 Aug 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Flow Cytometry
  • Malaria / immunology*
  • Malaria / prevention & control*
  • Malaria Vaccines / immunology*
  • Malaria Vaccines / therapeutic use
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Vaccination
  • Vaccines, Subunit / immunology*
  • Vaccines, Subunit / therapeutic use*

Substances

  • Epitopes, T-Lymphocyte
  • Malaria Vaccines
  • Vaccines, Subunit

Grants and funding

This work was supported by NHMRC Program Grant 496600. DLD was supported by a Pfizer Australia Senior Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.