Sequential immunization with heterologous chimeric flaviviruses induces broad-spectrum cross-reactive CD8+ T cell responses.
Flavivirus vaccines based on ChimeriVax technology contain the nonstructural genes of the yellow fever vaccine and the premembrane and envelope genes of heterologous flaviviruses, such as Japanese encephalitis and West Nile viruses. These chimeric vaccines induce both humoral and cell-mediated immunity. Mice were vaccinated with yellow fever, chimeric Japanese encephalitis virus (YF/JE), or chimeric West Nile virus (YF/WN) vaccines, followed by a secondary homologous or heterologous vaccination; the hierarchy and function of CD8(+) T cell responses to a variable envelope epitope were then analyzed and compared with those directed against a conserved immunodominant yellow fever virus NS3 epitope. Sequential vaccination with heterologous chimeric flaviviruses generated a broadly cross-reactive CD8(+) T cell response dependent on both the sequence of infecting viruses and epitope variant. The enhanced responses to variant epitopes after heterologous vaccination were not related to preexisting antibody or to higher virus titers. These results demonstrate that the sequence of vaccination affects the expansion of cross-reactive CD8(+) T cells after heterologous chimeric flavivirus challenge.
Singh
Rekha
R
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Rothman
Alan L
AL
Potts
James
J
Guirakhoo
Farshad
F
Ennis
Francis A
FA
Green
Sharone
S
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005416:Flavivirus / Q000276:immunology / Q000502:physiology; D018177:Flavivirus Infections / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics; D010948:Viral Plaque Assay; D014779:Virus Replication
D000939:Epitopes; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; D007371:Interferon-gamma