Protective cytotoxic T lymphocyte responses against paramyxoviruses induced by epitope-based DNA vaccines: involvement of IFN-gamma.
Plasmid DNA vectors have been constructed with minigenes encoding a single cytotoxic T lymphocyte (CTL) epitope from either the M2 protein of respiratory syncytial virus (RSV) or from the nucleoprotein of measles virus (MV) with or without a signal sequence (also called secretory or leader sequence). Following intradermal immunization, plasmids in which the CTL epitopes were expressed in-frame with the signal sequence were more effective at inducing peptide- and virus-specific CTL responses than plasmids expressing CTL epitopes without the signal sequence. This immunization resulted in protection against MV-induced encephalitis and a significant reduction in viral load following RSV challenge. The reduction of viral load following RSV challenge was abrogated by prior injection with anti-IFN-gamma antibodies. These results highlight the ability of epitope-based DNA immunization to induce protective immune responses to well-defined epitopes and indicate the potential of this approach for the development of vaccines against infectious diseases.
Hsu
S C
SC
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK.
Obeid
O E
OE
Collins
M
M
Iqbal
M
M
Chargelegue
D
D
Steward
M W
MW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004660:Encephalitis / Q000209:etiology / Q000517:prevention & control; D000939:Epitopes / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D007371:Interferon-gamma / Q000502:physiology; D008457:Measles / Q000150:complications / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control; D018108:Respirovirus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology
D000939:Epitopes; D019444:Vaccines, DNA; D007371:Interferon-gamma