T Cell Responses to Viral Infections – Opportunities for Peptide Vaccination

Abstract

An effective immune response against viral infections depends on the activation of cytotoxic T cells that can clear infection by killing virus-infected cells. Proper activation of these T cells depends on professional antigen-presenting cells, such as dendritic cells (DCs). In this review, we will discuss the potential of peptide-based vaccines for prevention and treatment of viral diseases. We will describe features of an effective response against both acute and chronic infections, such as an appropriate magnitude, breadth, and quality and discuss requirements for inducing such an effective antiviral immune response. We will address modifications that affect presentation of vaccine components by DCs, including choice of antigen, adjuvants, and formulation. Furthermore, we will describe differences in design between preventive and therapeutic peptide-based vaccines. The ultimate goal in the design of preventive vaccines is to develop a universal vaccine that cross-protects against multiple strains of the virus. For therapeutic vaccines, cross-protection is of less importance, but enhancing existing T cell responses is essential. Although peptide vaccination is successful in inducing responses in human papillomavirus (HPV) infected patients, there are still several challenges such as choosing the right target epitopes, choosing safe adjuvants that improve immunogenicity of these epitopes, and steering the immune response in the desired direction. We will conclude with an overview of the current status of peptide vaccination, hurdles to overcome, and prospects for the future.

Structure and Function of HLA-A*02-Restricted Hantaan Virus Cytotoxic T-Cell Epitope That Mediates Effective Protective Responses in HLA-A2.1/Kb Transgenic Mice

“…For prevention of infectious diseases, the use of therapeutic or prophylactic vaccines can be a successful method for directing the immune system against specific pathogens. A peptide vaccine with greater efficacy against pathogens would bring about a major improvement in protection of the population against infection (38)(39)(40). Our previous findings that the T-cell response was an important component of naturally acquired immunity to control HTNV infection provide the foundation for the development of HTNV peptide vaccines that may combat HTNV by efficiently inducing specific T-cell immunities.…”

“…However, due to MHC restrictions and low immunogenicity, the broad applicability of peptide vaccines for diseases may be currently limited. Several studies on various clinical applications of peptide vaccines have suggested that many potential variables, such as the type and length of peptides, the loading of one or multiple peptides on antigen-presenting cells (APCs) or the route of administration may attribute to the design efficiency of peptide vaccines (25,39,40). Selecting the right epitope is the first crucial step in the design of an effective vaccine.…”

Hepatitis E virus ORF 1 induces proliferative and functional T‐cell responses in patients with ongoing and resolved hepatitis E

“…Therefore, adding adjuvants might induce detectable T‐cell responses in this approved vaccine. Even a combination of the Hecolin ® vaccine together with peptides encoded by ORF1 and/or ORF2/3 in combination with an adjuvant might be considered …”

Effects of Dendritic Cells from Hepatitis B Virus Transgenic Mice-Stimulated Autologous Lymphocytes on Hepatitis B Virus Replication: A Study on the Impact of Specific Sensitized Effector Cells on In Vitro Virus Replication

“…(12) As the most powerful APC in vivo, DCs are able to uptake antigens, then process and present them to T-cells to initiate the corresponding immune response, thereby enhancing specific anti-HBV capacity and improving the patient's active immunity. (22) Here, we studied the effects of dendritic cells on HBV transgenic mice-stimulated autologous lymphocytes on in vitro HBV replication, with an emphasis on covalently closed circular DNA (cccDNA). Our goal was to evaluate changes in specific immune function after HBV infection and its relationship with HBV replication.…”