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INDUCTION OF NEUTRALIZING ANTIBODIES SPECIFIC TO DENGUE VIRUS SEROTYPES 2 AND 4 BY A BIVALENT ANTIGEN COMPOSED OF LINKED ENVELOPE DOMAINS III OF THESE TWO SEROTYPES

There is no vaccine to prevent dengue fever, a mosquito-borne viral disease, caused by four serotypes of dengue viruses. In this study, which has been prompted by the emergence of dengue virus envelope domain III as a promising sub-unit vaccine candidate, we have examined the possibility of developing a chimeric bivalent antigen with the potential to elicit neutralizing antibodies against two serotypes simultaneously. We created a chimeric dengue antigen by splicing envelope domain IIIs of serotypes 2 and 4. It was expressed in Escherichia coli and purified to near homogeneity. This protein retains the antigenic identitities of both its precursors. It elicited antibodies that could efficiently block host cell binding of both serotypes 2 and 4 of dengue virus and neutralize their infectivity (neutralizing antibody titers approximately 1:40 and ~1:80 for dengue virus serotypes 2 and 4, respectively). This work could be a forerunner to the development of a single envelope domain III-based tetravalent antigen.

Received June 1, 2005. Accepted for publication September 13, 2005.

Acknowledgments: We thank Dr. Andrew Falconar for providing all four serotypes of dengue virus.

Financial support: The work was supported by International Centre for Genetic Engineering and Biotechnology core funds. Saima Khanam is a senior research fellow supported by the Council of Scientific and Industrial Research, Government of India, India. Behzad Etemad is supported by an International Centre for Genetic Engineering and Biotechnology pre-doctoral fellowship.

^* Address correspondence to Sathyamangalam Swaminathan, RGP Group, P.O. Box 10504, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India. E-mail: swami{at}icgeb.res.in

Authors’ address: Saima Khanam, Behzad Etemad, Navin Khanna, and Sathyamangalam Swaminathan, Recombinant Gene Products Group, P.O. Box 10504, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India, Telephone: 91-11-2617-7357 Extension 271, Fax: 91-11-2616-2316, E-mails: amias7{at}rediffmail.com, tabbycatb{at}yahoo.com, navin{at}icgeb.res.in, and swami{at}icgeb.res.in.

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