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Journal of Virology, April 2007, p. 3514-3524, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02052-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Virus-Like Particle Vaccine Induces Protective Immunity against Homologous and Heterologous Strains of Influenza Virus{triangledown}

Fu-Shi Quan, Chunzi Huang, Richard W. Compans,* and Sang-Moo Kang*

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia

Received 19 September 2006/ Accepted 8 January 2007

Recurrent outbreaks of highly pathogenic avian influenza virus pose the threat of pandemic spread of lethal disease and make it a priority to develop safe and effective vaccines. Influenza virus-like particles (VLPs) have been suggested to be a promising vaccine approach. However, VLP-induced immune responses, and their roles in inducing memory immune responses and cross-protective immunity have not been investigated. In this study, we developed VLPs containing influenza virus A/PR8/34 (H1N1) hemagglutinin (HA) and matrix (M1) proteins and investigated their immunogenicity, long-term cross-protective efficacy, and effects on lung proinflammatory cytokines in mice. Intranasal immunization with VLPs containing HA induced high serum and mucosal antibody titers and neutralizing activity against PR8 and A/WSN/33 (H1N1) viruses. Mice immunized with VLPs containing HA showed little or no proinflammatory lung cytokines and were protected from a lethal challenge with mouse-adapted PR8 or WSN viruses even 5 months postimmunization. Influenza VLPs induced mucosal immunoglobulin G and cellular immune responses, which were reactivated rapidly upon virus challenge. Long-lived antibody-secreting cells were detected in the bone marrow of immunized mice. Immune sera administered intranasally were able to confer 100% protection from a lethal challenge with PR8 or WSN, which provides further evidence that anti-HA antibodies are primarily responsible for preventing infection. Taken together, these results indicate that nonreplicating influenza VLPs represent a promising strategy for the development of a safe and effective vaccine to control the spread of lethal influenza viruses.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322. Phone for Richard W. Compans: (404) 727-5950. Fax: (404) 727-8250. E-mail: compans{at}microbio.emory.edu. Phone for Sang-Moo Kang: (404) 727-3228. Fax: (404) 727-3659. E-mail: skang2{at}emory.edu.

{triangledown} Published ahead of print on 24 January 2007.

Journal of Virology, April 2007, p. 3514-3524, Vol. 81, No. 7
0022-538X/07/$08.00+0     doi:10.1128/JVI.02052-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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