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Clinical and Vaccine Immunology, August 2007, p. 969-977, Vol. 14, No. 8
1071-412X/07/$08.00+0     doi:10.1128/CVI.00069-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cross-Reactive T-Cell Responses to the Nonstructural Regions of Dengue Viruses among Dengue Fever and Dengue Hemorrhagic Fever Patients in Malaysia{triangledown}

Ramapraba Appanna,1,{dagger} Tan Lian Huat,2,{dagger} Lucy Lum Chai See,3,{dagger} Phoay Lay Tan,4,{dagger} Jamuna Vadivelu,1,{dagger} and Shamala Devi1,{dagger}*

Department of Medical Microbiology, Faculty of Medicine, University Malaya, 50603, Kuala Lumpur, Malaysia,1 Department of Medicine, Faculty of Medicine, University Malaya Medical Centre, University Hospital, 50603, Kuala Lumpur, Malaysia,2 Department of Paediatrics, Faculty of Medicine, University Malaya Medical Centre, University Hospital, 50603, Kuala Lumpur, Malaysia,3 Department of Primary Care Medicine, Faculty of Medicine, University Malaya, 50603, Kuala Lumpur, Malaysia4

Received 2 February 2007/ Returned for modification 25 April 2007/ Accepted 28 May 2007

Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas in the world. Attempts to develop effective vaccines have been hampered by the lack of understanding of the pathogenesis of the disease and the absence of suitable experimental models for dengue viral infection. The magnitude of T-cell responses has been reported to correlate with dengue disease severity. Sixty Malaysian adults with dengue viral infections were investigated for their dengue virus-specific T-cell responses to 32 peptides antigens from the structural and nonstructural regions from a dengue virus isolate. Seventeen different peptides from the C, E, NS2B, NS3, NS4A, NS4B, and NS5 regions were found to evoke significant responses in a gamma interferon enzyme-linked immunospot (ELISPOT) assay of samples from 13 selected patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). NS3 and predominantly NS3422-431 were found to be important T-cell targets. The highest peaks of T-cell responses observed were in responses to NS3422-431 and NS5563-571 in DHF patients. We also found almost a sevenfold increase in T-cell response in three DHF patients compared to three DF patient responses to peptide NS3422-431. A large number of patients' T cells also responded to the NS2B97-106 region. The ELISPOT analyses also revealed high frequencies of T cells that recognize both serotype-specific and cross-reactive dengue virus antigens in patients with DHF.

* Corresponding author. Mailing address: University Malaya, Medical Microbiology, Faculty of Medicine, Kuala Lumpur 50603, Malaysia. Phone: 6-0379-675759. Fax: 6-0379-584844. E-mail: shamalamy{at}yahoo.com

{triangledown} Published ahead of print on 13 June 2007.

{dagger} R.A. carried out the experimental work on ELISPOT and HLA typing; T.L.H., L.L.C.S., and P.L.T. assisted with collection of patients' information and disease classification; J.V. is the cosupervisor; S.D. is the grant holder and supervisor of the project and wrote the paper.

Clinical and Vaccine Immunology, August 2007, p. 969-977, Vol. 14, No. 8
1071-412X/07/$08.00+0     doi:10.1128/CVI.00069-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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