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Journal of Virology, September 1999, p. 7497-7504, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Expression of Noncovalent Hepatitis C Virus Envelope E1-E2 Complexes Is Not Required for the Induction of Antibodies with Neutralizing Properties following DNA Immunization

A. Fournillier,1 E. Depla,2 P. Karayiannis,3 O. Vidalin,1 G. Maertens,2 C. Trépo,1 and G. Inchauspé1,*

INSERM U271, Virus des hépatites, Rétrovirus humains et Pathologies associées, 69424 Lyon Cédex, France1; Hepatitis Program, INNOGENETICS, B-9052 Ghent, Belgium2; and Imperial College School of Medicine at St. Mary's, Department of Medicine, London W2 INY, United Kingdom3

Received 17 February 1999/Accepted 4 June 1999

Interactive glycoproteins present on the surface of viral particles represent the main target of neutralizing antibodies. The ability of DNA vaccination to induce antibodies directed at such structures was investigated by using eight different expression plasmids engineered either to favor or to prevent interaction between the hepatitis C virus (HCV) envelope glycoproteins E1 and E2. Independently of the injection route (intramuscular or intraepidermal), plasmids expressing antigens capable of forming heterodimers presumed to be the prebudding form of the HCV envelope protein complex failed to induce any significant, stable antibodies following injection in mice. In sharp contrast, high titers of antibodies directed at both conformational and linear determinants were induced by using plasmids expressing severely truncated antigens that have lost the ability to form native complexes. In addition, only a truncated form of E2 induced antibodies reacting against the hypervariable region 1 of E2 (specifically with the C-terminal part of it) known to contain a neutralization site. When injected intraepidermally into small primates, the truncated E2-encoding plasmid induced antibodies able to neutralize in vitro the binding of a purified E2 protein onto susceptible cells. Because such antibodies have been associated with viral clearance in both humans and chimpanzees, these findings may have important implications for the development of protective immunity against HCV.

* Corresponding author. Mailing address: INSERM U271, 151 Cours Albert Thomas, Lyon 69424, France. Phone: 33.4.72.68.19.88. Fax: 33.4.72.68.19.71. E-mail: inchauspe{at}lyon151.inserm.fr.

Journal of Virology, September 1999, p. 7497-7504, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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