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Journal of Virology, December 2001, p. 11457-11463, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11457-11463.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Protective Mechanisms Induced by a Japanese Encephalitis Virus DNA Vaccine: Requirement for Antibody but Not CD8+ Cytotoxic T-Cell Responses

Chien-Hsiung Pan,1,2 Hsin-Wei Chen,2,dagger Hui-Wen Huang,2 and Mi-Hua Tao2,*

Graduate Institute of Life Sciences, National Defense Medical Center,1 and Institute of Biomedical Sciences, Academia Sinica,2 Taipei, Taiwan

Received 27 June 2001/Accepted 5 September 2001

We have previously shown that a plasmid (pE) encoding the Japanese encephalitis virus (JEV) envelope (E) protein conferred a high level of protection against a lethal viral challenge. In the present study, we used adoptive transfer experiments and gene knockout mice to demonstrate that the DNA-induced E-specific antibody alone can confer protection in the absence of cytotoxic T-lymphocyte (CTL) functions. Plasmid pE administered by either intramuscular or gene gun injection produced significant E-specific antibodies, helper T (Th)-cell proliferative responses, and CTL activities. Animals receiving suboptimal DNA vaccination produced low titers of anti-E antibodies and were only partially or not protected from viral challenge, indicating a strong correlation between anti-E antibodies and the protective capacity. This observation was confirmed by adoptive transfer experiments. Intravenous transfer of E-specific antisera but not crude or T-cell-enriched immune splenocytes to sublethally irradiated hosts conferred protection against a lethal JEV challenge. Furthermore, experiments with gene knockout mice showed that DNA vaccination did not induce anti-E titers and protective immunity in Igµ-/- and I-Abeta -/- mice, whereas in CD8alpha -/- mice the pE-induced antibody titers and protective rate were comparable to those produced in the wild-type mice. Taken together, these results demonstrate that the anti-E antibody is the most critical protective component in this JEV challenge model and that production of anti-E antibody by pE DNA vaccine is dependent on the presence of CD4+ T cells but independent of CD8+ T cells.

* Corresponding author. Mailing address: 128 Yen-Chiu-Yuan Rd., Sec. 2, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 11529. Phone: 886-2-2652-3078. Fax: 886-2-2782-9142. E-mail: bmtao{at}ibms.sinica.edu.tw.

dagger Present address: National Health Research Institutes, Taipei, Taiwan.

Journal of Virology, December 2001, p. 11457-11463, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11457-11463.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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