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Peptide Vaccine: Progress and Challenges.

Li W, Joshi MD, Singhania S, Ramsey KH, Murthy AK - Vaccines (Basel) (2014)

Bottom Line: Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting.In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases.Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Midwestern University, Downers Grove, IL 60515, USA. wli@midwestern.edu.

ABSTRACT
Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

No MeSH data available.


Related in: MedlinePlus

Central role of CD4+ T cells in peptide vaccines. Vaccine-induced immune response to control microbial pathogens may involve cytotoxic CD8+ T cell responses, helper CD4+ T cell responses, or antibody (B cell) responses. T cells recognize linear epitopes presented by antigen presenting cells, whereas B cells are capable of recognizing linear and conformational epitopes on soluble antigens. The induction of robust CD8+ T cell and/or antibody responses requires cytokine help from CD4+ T cells. Therefore, regardless of the nature of protective immune response required, the induction of CD4+ T cell responses is critical.
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vaccines-02-00515-f001: Central role of CD4+ T cells in peptide vaccines. Vaccine-induced immune response to control microbial pathogens may involve cytotoxic CD8+ T cell responses, helper CD4+ T cell responses, or antibody (B cell) responses. T cells recognize linear epitopes presented by antigen presenting cells, whereas B cells are capable of recognizing linear and conformational epitopes on soluble antigens. The induction of robust CD8+ T cell and/or antibody responses requires cytokine help from CD4+ T cells. Therefore, regardless of the nature of protective immune response required, the induction of CD4+ T cell responses is critical.

Mentions: The impact of CD4 helper T cells in peptide vaccination was proven by subsequent studies in many model systems, and has been depicted in Figure 1. For example, the LCMV 15-mer synthetic long peptide vaccination study revealed that the effectiveness of LCMV 15-mer peptides to induce LCMV-specific CD8 T cell reactivity depended on CD4 T-cell help, suggesting that these 15-mer peptides comprised a helper epitope [53,54]. Similar results came from a HPV16 E7 peptide vaccination study in which the HPV16 E7 peptide vaccine in Freund’s incomplete adjuvant (FIA) failed to induce strong peptide-specific CD8 T-cell response in MHC-II knockout mice. This peptide comprised a T helper epitope that overlaps with the CTL epitope [55,56,57,58]. These data suggest that activation of antigen specific helper cells by peptide, comprising helper-epitopes, is very important for development of peptide vaccines, and the generation of protective CD8 T cell response is clearly improved after addition of T helper peptides. Longer peptides can be taken up by professional APC, proteolytically processed, and then loaded onto appropriate MHC molecules and transported to the cell surface. It seems logical that the latest designed peptide vaccine should consist of multi epitopes, which could include the MHC II restricted helper epitopes recognized by CD4 T cells and MHC I restricted CD8 epitopes to induce both helper T cells and CTL, or include T and B epitopes to elicit the specific T cells and humoral responses.


Peptide Vaccine: Progress and Challenges.

Li W, Joshi MD, Singhania S, Ramsey KH, Murthy AK - Vaccines (Basel) (2014)

Central role of CD4+ T cells in peptide vaccines. Vaccine-induced immune response to control microbial pathogens may involve cytotoxic CD8+ T cell responses, helper CD4+ T cell responses, or antibody (B cell) responses. T cells recognize linear epitopes presented by antigen presenting cells, whereas B cells are capable of recognizing linear and conformational epitopes on soluble antigens. The induction of robust CD8+ T cell and/or antibody responses requires cytokine help from CD4+ T cells. Therefore, regardless of the nature of protective immune response required, the induction of CD4+ T cell responses is critical.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494216&req=5

vaccines-02-00515-f001: Central role of CD4+ T cells in peptide vaccines. Vaccine-induced immune response to control microbial pathogens may involve cytotoxic CD8+ T cell responses, helper CD4+ T cell responses, or antibody (B cell) responses. T cells recognize linear epitopes presented by antigen presenting cells, whereas B cells are capable of recognizing linear and conformational epitopes on soluble antigens. The induction of robust CD8+ T cell and/or antibody responses requires cytokine help from CD4+ T cells. Therefore, regardless of the nature of protective immune response required, the induction of CD4+ T cell responses is critical.
Mentions: The impact of CD4 helper T cells in peptide vaccination was proven by subsequent studies in many model systems, and has been depicted in Figure 1. For example, the LCMV 15-mer synthetic long peptide vaccination study revealed that the effectiveness of LCMV 15-mer peptides to induce LCMV-specific CD8 T cell reactivity depended on CD4 T-cell help, suggesting that these 15-mer peptides comprised a helper epitope [53,54]. Similar results came from a HPV16 E7 peptide vaccination study in which the HPV16 E7 peptide vaccine in Freund’s incomplete adjuvant (FIA) failed to induce strong peptide-specific CD8 T-cell response in MHC-II knockout mice. This peptide comprised a T helper epitope that overlaps with the CTL epitope [55,56,57,58]. These data suggest that activation of antigen specific helper cells by peptide, comprising helper-epitopes, is very important for development of peptide vaccines, and the generation of protective CD8 T cell response is clearly improved after addition of T helper peptides. Longer peptides can be taken up by professional APC, proteolytically processed, and then loaded onto appropriate MHC molecules and transported to the cell surface. It seems logical that the latest designed peptide vaccine should consist of multi epitopes, which could include the MHC II restricted helper epitopes recognized by CD4 T cells and MHC I restricted CD8 epitopes to induce both helper T cells and CTL, or include T and B epitopes to elicit the specific T cells and humoral responses.

Bottom Line: Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting.In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases.Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Midwestern University, Downers Grove, IL 60515, USA. wli@midwestern.edu.

ABSTRACT
Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

No MeSH data available.


Related in: MedlinePlus