Enhanced CTL response by controlled intracellular trafficking of antigen in dendritic cells following DNA vaccination

Injection site‐dependent induction of immune response by DNA vaccine: comparison of skin and spleen as a target for vaccination

“…pCMV‐OVA was a kind of gift from Dr Shoshana Levy (Department of Medicine/Oncology, Stanford University Medical Centre, Stanford, CA, USA) 21. The construction of pPep‐ER has been reported elsewhere 20. In brief, oligodeoxynucleotides corresponding to the sequence of SIINFEKL peptide were annealed, then inserted into the Sal I‐ Not I restriction site of the multiple cloning site of pCMV/myc/ER Shoot vector (Invitrogen, Carlsbad, CA, USA).…”

“…pCMV‐OVA is considered to mainly undergo cross‐presentation, because the model antigen, OVA, is secreted from transduced cells and taken up by professional APCs for antigen presentation 16–19. On the other hand, pPep‐ER was developed as a novel vector in our laboratory, by which an antigen peptide is expressed and bound to the major histocompatibility complex (MHC) class I molecule without being secreted from transduced cells 20.…”

Genetic Immunization with Plasmid DNA Mediated by Electrotransfer

“…For example, adding an endoplasmic reticulum retention signal fused to the antigen enhances the CTL response (Isagi et al, 2009). Several studies have also indicated that a secreted form of the antigen leads to a higher immune response and more neutralizing antibodies (Geissler et al, 1999;Ashok and Rangarajan, 2002).…”

Hepatitis B Surface Antigen-based Vaccines for Human Neoplastic Disease

“…When humans were immunised as part of a clinical trial with HBsAg-encoding DNA vaccine, protective levels of HBsAg-specific antibody response were achieved in all volunteers as well as CD8 + T-cell responses in HLA-A2 volunteers, which were able to kill cells expressing HBsAg epitopes (Roy et al, 2000a). Native transmembrane domains of HBsAg target the antigen to the secretory pathway via the ER (Johansson et al, 2007;Mwangi et al, 2007;Isaji et al, 2009). A number of studies have shown that DNA-based chimeric polyepitope vaccines and epitopes that are targeted to the ER enhance the cytotoxic CD8-mediated CTL response to these epitopes (Anton et al, 1997;Xu et al, 2005a;Kreiter et al, 2008) and correlate with protection against viral infection (Ishioka et al, 1999;Hahn et al, 2004;Pinchuk et al, 2005) and tumour growth (Minev et al, 2000;Sherritt et al, 2001;Aladin et al, 2007).…”

“…Such targeting has been previously suggested to be a cause of the enhanced immunogenicity of HBsAg molecules (Minev et al, 2000;Sherritt et al, 2001;Xu et al, 2005a;Isaji et al, 2009). As the generation of VLPs from a DNA vaccine is not necessary for immunogenicity, a future direction should involve studies of HBsAg to eliminate unnecessary HBsAg sequence (and potential CD8 CTL epitopes), while maintaining the inherent ability to enhance immunogenicity.…”