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J. Virol. doi:10.1128/JVI.00923-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A vectored measles virus induces hepatitis B surface antigen antibodies while protecting macaques against measles challenge

Molecular Medicine Program and Virology and Gene Therapy Graduate Track, Mayo Clinic College of Medicine, Rochester MN, 55905, USA, California National Primate Research Center, and Department of Pathology and Laboratory Medicine, School of Medicine, University of California-Davis, Davis CA 95616, USA

^* To whom correspondence should be addressed. Email: cattaneo.roberto{at}mayo.edu.

	Abstract

Hepatitis B virus (HBV) acute and chronic infections remain a major worldwide health problem. Towards developing an anti-HBV vaccine with a single-dose scheme potential, we engineered infectious measles virus (MV) genomic cDNAs with vaccine strain background and expression vector properties. Hepatitis B surface antigen (HBsAg) expression cassettes were inserted in this cDNA, and three MV expressing HBsAg at different levels generated. All vectored MV, which secrete HBsAg as subviral particles, elicited humoral responses in MV-susceptible genetically modified mice. However, small differences in HBsAg expression elicited vastly different HBsAg antibody levels. The two vectors inducing the highest HBsAg antibody levels were inoculated in rhesus monkeys (Macaca mulatta). After challenge with a pathogenic MV strain (Davis₈₇), control naïve monkeys showed a classic measles rash and high viral loads. In contrast, all monkeys immunized with vaccine, or a control non-vectored recombinant vaccine, or HBsAg-expressing vectored MV, remained healthy with low or undetectable viral loads. After a single vaccine dose, only the vector expressing HBsAg at the highest levels elicited protective levels of HBsAg antibodies in two of four animals. These observations reveal an expression threshold for efficient induction of HBsAg humoral immune responses. This threshold is lower in mice than in macaques. Implications for the development of divalent vaccines based on live attenuated viruses are discussed.

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