Antibody‐Dependent Cellular Cytotoxicity Mediated by Plasma Obtained before Secondary Dengue Virus Infections: Potential Involvement in Early Control of Viral Replication
1Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester; 2Department of Virus Diseases, Walter Reed Army Institute of Research, Washington, DC; 3Department of Pediatrics, Prince of Songkla University, Songkhla, and 4Department of Virology, US Army Medical Component, Armed Forces Research Institute of Medical Sciences, and 5Division of General Communicable Diseases, Department of Communicable Disease Control, Ministry of Public Health, Bangkok, Thailand
Background.
Preexisting dengue virus (DV)–specific antibodies from prior heterologous DV infection may have several effects in secondary DV infection. These antibodies may mediate protective effects by means of antibody‐dependent cellular cytotoxicity (ADCC), in which virus‐specific antibodies bind to the surface of heterologous DV‐infected cells and mediate natural killer cell lysis. In the present study, we examined the ability of plasma obtained before secondary DV infection to induce ADCC of DV‐infected cells.
Methods.Plasma samples were obtained before DV2 or DV3 infection in a prospective cohort study of Thai schoolchildren. The ADCC activity in the plasma samples was measured by 51Cr‐release assay, using persistently DV2‐ or DV3‐infected Raji cells as targets.
Results.ADCC activity in plasma obtained before secondary infection directly correlated with neutralizing antibody titers, anti‐DV immunoglobulin G1 levels, and a multitypic 50% plaque reduction neutralization test pattern. ADCC activity in pre–secondary DV3 infection plasma samples inversely correlated with plasma viremia levels, but no such correlation was seen in pre–secondary DV2 infection plasma samples. ADCC activity did not correlate with disease severity in subsequent secondary DV2 or DV3 infection but was lowest in plasma from patients with dengue hemorrhagic fever due to secondary DV3 infection.
Conclusions.ADCC may contribute to the early control of secondary DV3 viremia in vivo.
Received 8 August 2006; accepted 22 November 2006; electronically published 7 March 2007
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Online publication date: 1-Oct-2007.
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Potential conflicts of interest: none reported.
Presented in part: 53rd Annual Meeting of the American Society of Tropical Medicine and Hygiene, Miami, FL, 9 November 2004; 54th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Washington, DC, 13 December 2005 (abstract 520).
Financial support: National Institutes of Health (grants P01 AI34533 and U19 AI057319 and grant K08 AI01729 to S.G.); US Army Medical Research and Materiel Command.
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Present affiliation: Infectious Disease Division, State University of New York, Upstate Medical University, Syracuse.