Most importantly, the epitope approach has been used successfully to treat and/or prevent different types of disease in animal models, including acute or chronic viral infections, ,, , parasitic and microbial infections, and cancer. Epitope-based immunization has been shown to be effective in eliciting responses against multiple B cell, CD4 + T cell or CD8 + T cell epitopes, including subdominant CD8 + T cell epitopes –. Further advantages of epitope-based vaccines over current vaccines include increased potency and other qualitative aspects of the immune response, particularly when compared to the use of whole antigens. Synthetic peptide-based vaccines offer many advantages over whole-organism vaccines due their amenability to large-scale production, their well-defined composition and purity, and their suitability for freeze-drying which eliminates the need for the cold-chain. Such failures highlight the need for a redirection of subunit vaccine approaches. However, the leading asexual blood-stage and liver-stage recombinant protein subunit vaccines candidates against malaria (MSP1, AMA1 and LSA1) have all failed in recent phase 2a experimental challenge studies and phase 2b field trials despite induction of high antibody titre, growth inhibitory activity, and CD4 + T cell responses. Recombinant protein-based subunit vaccines have been widely evaluated in many disease systems, including malaria. Subunit vaccines have a range of advantages over the use of whole pathogenic microorganisms, including: improved stability, reduced risk of autoimmunity and allergic responses, no risk of reversion to the virulent form, ability to direct immune responses towards a specified antigen or epitope, and capacity for large-scale production under good manufacturing conditions. Vaccines which contain the minimal microbial components necessary to stimulate appropriate immune responses are referred to as subunit vaccines. Almost all licensed vaccines are based on the delivery of live, attenuated, or killed whole pathogens. Vaccines are one of the most cost effective and efficient health care interventions for the prevention of infectious diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. DLD was supported by a Pfizer Australia Senior Research Fellowship. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was supported by NHMRC Program Grant 496600. Received: JanuAccepted: JPublished: August 24, 2012Ĭopyright: © Apte et al. (2012) Vaccination with Lipid Core Peptides Fails to Induce Epitope-Specific T Cell Responses but Confers Non-Specific Protective Immunity in a Malaria Model. 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.Ĭitation: Apte SH, Groves PL, Skwarczynski M, Fujita Y, Chang C, Toth I, et al. These non-specific responses were able to protect against parasite challenge. Cytotoxic responses of unknown specificity were also induced. 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. We show that LCP vaccines failed to induce an expansion of antigen-specific CD8 + T cells following primary immunization or by boosting. 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. 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. 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. Synthetic peptide-based vaccines offer an attractive alternative to whole protein and whole organism vaccines, particularly for complex pathogens that cause chronic infection. Vaccines against many pathogens for which conventional approaches have failed remain an unmet public health priority.
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