Title

Sequential immunization with heterologous chimeric flaviviruses induces broad-spectrum cross-reactive CD8+ T cell responses

UMMS Affiliation

Center for Infectious Disease and Vaccine Research; Division of Infectious Diseases and Immunology, Department of Medicine

Publication Date

7-15-2010

Document Type

Article

Disciplines

Immunity | Immunology and Infectious Disease | Immunology of Infectious Disease | Infectious Disease

Abstract

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.

Rights and Permissions

Citation: J Infect Dis. 2010 Jul 15;202(2):223-33. doi: 10.1086/653486. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of infectious diseases

Related Resources

Link to Article in PubMed

PubMed ID

20536361