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Journal of Virology, June 2005, p. 7380-7388, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7380-7388.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Universal Influenza B Vaccine Based on the Maturational Cleavage Site of the Hemagglutinin Precursor

Elisabetta Bianchi,1 Xiaoping Liang,2 Paolo Ingallinella,1 Marco Finotto,1 Michael A. Chastain,2 Jiang Fan,2 Tong-Ming Fu,2 Hong Chang Song,2 Melanie S. Horton,2 Daniel C. Freed,2 Walter Manger,2 Emily Wen,2 Li Shi,2 Roxana Ionescu,2 Colleen Price,2 Marc Wenger,2 Emilio A. Emini,2,{dagger} Riccardo Cortese,1 Gennaro Ciliberto,1 John W. Shiver,2 and Antonello Pessi1*

IRBM P. Angeletti, Via Pontina Km 30.600, 00040 Pomezia (Rome), Italy,1 Merck Research Laboratories, 770 Sumneytown Pike, P. O. Box 4, WP26-381, West Point, Pennsylvania 194862

Received 12 October 2004/ Accepted 19 February 2005

Conventional influenza vaccines can prevent infection, but their efficacy depends on the degree of antigenic "match" between the strains used for vaccine preparation and those circulating in the population. A universal influenza vaccine based on invariant regions of the virus, able to provide broadly cross-reactive protection, without requiring continuous manufacturing update, would solve a major medical need. Since the temporal and geographical dominance of the influenza virus type and/or subtype (A/H3, A/H1, or B) cannot yet be predicted, a universal vaccine, like the vaccines currently in use, should include both type A and type B influenza virus components. However, while encouraging preclinical data are available for influenza A virus, no candidate universal vaccine is available for influenza B virus. We show here that a peptide conjugate vaccine, based on the highly conserved maturational cleavage site of the HA0 precursor of the influenza B virus hemagglutinin, can elicit a protective immune response against lethal challenge with viruses belonging to either one of the representative, non-antigenically cross-reactive influenza B virus lineages. We demonstrate that protection by the HA0 vaccine is mediated by antibodies, probably through effector mechanisms, and that a major part of the protective response targets the most conserved region of HA0, the P1 residue of the scissile bond and the fusion peptide domain. In addition, we present preliminary evidence that the approach can be extended to influenza A virus, although the equivalent HA0 conjugate is not as efficacious as for influenza B virus.

* Corresponding author. Mailing address: Department of Molecular & Cell Biology, IRBM P. Angeletti, Via Pontina Km 30.600, 00040 Pomezia (Rome) Italy. Phone: 39-06-9109344. Fax: 39-06-91093654. E-mail: antonello_pessi{at}merck.com.

{dagger} Present address: International AIDS Vaccine Initiative, 110 William Street, 27th Floor, New York, NY 10038.

Journal of Virology, June 2005, p. 7380-7388, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7380-7388.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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