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J. Virol. doi:10.1128/JVI.02052-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Virus-like particle vaccine induces protective immunity against homologous and heterologous strains of influenza virus

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

^* To whom correspondence should be addressed. Email: compans{at}microbio.emory.edu. skang2{at}emory.edu.

	Abstract

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 A/PR8/34 (H1N1) hemagglutinin (HA) and matrix (M1) proteins, and investigated their immunogenicity, long-term cross-protective efficacy, and effects on lung pro-inflammatory cytokines in mice. Intranasal immunization with VLPs containing HA induced high serum and mucosal antibody titers, and neutralizing activity against PR8 as well as A/WSN/33 (H1N1) viruses. Mice immunized with VLPs containing HA showed little or no pro-inflammatory lung cytokines and were protected from a lethal challenge with mouse-adapted PR8 or WSN viruses even 5 months post-immunization. Influenza VLPs induced mucosal IgG 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 when 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 non-replicating influenza VLPs represent a promising strategy for the development of a safe and effective vaccine to control the spread of lethal influenza viruses.

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