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Clinical and Diagnostic Laboratory Immunology, October 2005, p. 1157-1163, Vol. 12, No. 10
1071-412X/05/$08.00+0     doi:10.1128/CDLI.12.10.1157-1163.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Evaluation of Serum Antibody Responses against the Rotavirus Nonstructural Protein NSP4 in Children after Rhesus Rotavirus Tetravalent Vaccination or Natural Infection

Esmeralda Vizzi,1* Eva Calviño,1 Rosabel González,2 Irene Pérez-Schael,2 Max Ciarlet,3,{dagger} Gagandeep Kang,3,{ddagger} Mary K. Estes,3 Ferdinando Liprandi,1 and Juan E. Ludert1

Laboratorio de Biología de Virus, Centro de Microbiología y Biología Celular, IVIC, Caracas, Venezuela,1 Instituto de Biomedicina, MSDS, UCV, Caracas, Venezuela,2 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas3

Received 9 May 2005/ Returned for modification 11 July 2005/ Accepted 14 August 2005

The immune response elicited by the rotavirus nonstructural protein NSP4 and its potential role in protection against rotavirus disease are not well understood. We investigated the serological response to NSP4 and its correlation with disease protection in sera from 110 children suffering acute diarrhea, associated or not with rotavirus, and from 26 children who were recipients of the rhesus rotavirus tetravalent (RRV-TV) vaccine. We used, as antigens in an enzyme-linked immunosorbent assay (ELISA), affinity-purified recombinant NSP4 (residues 85 to 175) from strains SA11, Wa, and RRV (genotypes A, B, and C, respectively) fused to glutathione S-transferase. Seroconversion to NSP4 was observed in 54% (42/78) of the children who suffered from natural rotavirus infection and in 8% (2/26) of the RRV-TV vaccine recipients. Our findings indicate that NSP4 evokes significantly (P < 0.05) higher seroconversion rates after natural infection than after RRV-TV vaccination. The serum antibody levels to NSP4 were modest (titers of ≤200) in most of the infected and vaccinated children. A heterotypic NSP4 response was detected in 48% of the naturally rotavirus-infected children with a detectable response to NSP4. Following natural infection or RRV-TV vaccination, NSP4 was significantly less immunogenic than the VP6 protein when these responses were independently measured by ELISA. A significant (P < 0.05) proportion of children who did not develop diarrhea associated with rotavirus had antibodies to NSP4 in acute-phase serum, suggesting that serum antibodies against NSP4 might correlate with protection from rotavirus diarrhea. In addition, previous exposures to rotavirus did not affect the NSP4 seroconversion rate.

* Corresponding author. Mailing address: Laboratorio de Biología de Virus, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas (IVIC), Carretera Panamericana Km 11, Caracas, 1020-A, Edo Miranda, Venezuela. Phone: 58-212-5041882. Fax: 58-212-5041655. E-mail: evizzi{at}ivic.ve.

{dagger} Present address: Biologics—Clinical Research, Merck & Co., Inc., Blue Bell, PA 19422.

{ddagger} Present address: Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.

Clinical and Diagnostic Laboratory Immunology, October 2005, p. 1157-1163, Vol. 12, No. 10
1071-412X/05/$08.00+0     doi:10.1128/CDLI.12.10.1157-1163.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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