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Journal of Virology, June 2005, p. 6674-6679, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.6674-6679.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Live Bivalent Vaccine for Parainfluenza and Influenza Virus Infections

Yasuko Maeda,1,2 Masato Hatta,2 Ayato Takada,1,3 Tokiko Watanabe,4 Hideo Goto,1,3 Gabriele Neumann,2 and Yoshihiro Kawaoka1,2,3*

Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan,1 Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama 332-0021, Japan,3 Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706,2 Institute for Molecular Virology, University of Wisconsin-Madison, Madison, Wisconsin 537064

Received 8 October 2004/ Accepted 24 January 2005

Influenza and human parainfluenza virus infections are of both medical and economical importance. Currently, inactivated vaccines provide suboptimal protection against influenza, and vaccines for human parainfluenza virus infection are not available, underscoring the need for new vaccines against these respiratory diseases. Furthermore, to reduce the burden of vaccination, the development of multivalent vaccines is highly desirable. Thus, to devise a single vaccine that would elicit immune responses against both influenza and parainfluenza viruses, we used reverse genetics to generate an influenza A virus that possesses the coding region for the hemagglutinin/neuraminidase ectodomain of parainfluenza virus instead of the influenza virus neuraminidase. The recombinant virus grew efficiently in eggs but was attenuated in mice. When intranasally immunized with the recombinant vaccine, all mice developed antibodies against both influenza and parainfluenza viruses and survived an otherwise lethal challenge with either of these viruses. This live bivalent vaccine has obvious advantages over combination vaccines, and its method of generation could, in principle, be applied in the development of a "cocktail" vaccine with efficacy against several different infectious diseases.

* Corresponding author. Mailing address: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81 3 5449 5504. Fax: 81 3 5449 5408. E-mail: kawaoka{at}ims.u-tokyo.ac.jp.

Journal of Virology, June 2005, p. 6674-6679, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.6674-6679.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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