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Journal of Virology, April 2009, p. 2803-2818, Vol. 83, No. 7
0022-538X/09/$08.00+0 doi:10.1128/JVI.02424-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

John Steel,1,
Samira Mubareka,1
Elena Carnero,1
Adolfo García-Sastre,1,2,3 and
Peter Palese1,2*
Department of Microbiology,1 Department of Medicine, Division of Infectious Diseases,2 Emerging Pathogens Institute, Mount Sinai School of Medicine, 1 Gustave Levy Pl., New York, New York 10029-65743
Received 24 November 2008/ Accepted 9 January 2009
Interventions aimed at preventing viral spread have the potential to effectively control influenza virus in all age groups, thereby reducing the burden of influenza illness. For this reason, we have examined the efficacy of vaccination in blocking the transmission of influenza viruses between guinea pigs. Three modes of immunization were compared: (i) natural infection; (ii) intramuscular administration of whole, inactivated influenza virus in 2 doses; and (iii) intranasal inoculation with live attenuated influenza virus in 2 doses. The ability of each immunization method to block the spread of a homologous (A/Panama/2007/99) H3N2 subtype and a heterologous (A/Wisconsin/67/05) H3N2 subtype influenza virus was tested. We found that previous infection through a natural route provided sterilizing immunity against both homologous and heterologous challenges; thus, no transmission to or from previously infected animals was observed. Vaccination with an inactivated influenza virus vaccine, in contrast, did not prevent guinea pigs from becoming infected upon challenge with either virus. Thus, both intranasal inoculation and exposure to an acutely infected guinea pig led to the infection of vaccinated animals. Vaccination with inactivated virus did, however, reduce viral load upon challenge and decrease the number of secondary transmission events from vaccinated animals to naïve cage mates. Vaccination with a live attenuated virus was found to be more efficacious than vaccination with inactivated virus, resulting in sterilizing immunity against homologous challenge and full protection against the transmission of the homologous and heterologous viruses to naïve contacts. In conclusion, we have shown that the guinea pig model can be used to test influenza virus vaccines and that the efficiency of transmission is a valuable readout when vaccine efficacy is evaluated.
Published ahead of print on 19 January 2009.
A.C.L. and J.S. contributed equally to this work.
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