Abstract
BackgroundThe 2009 influenza pandemic and shortages in vaccine supplies worldwide underscore the need for new approaches to develop more effective vaccines.Methodology/Principal FindingsWe generated influenza virus-like particles (VLPs) containing proteins derived from the A/California/04/2009 virus, and tested their efficacy as a vaccine in mice. A single intramuscular vaccination with VLPs provided complete protection against lethal challenge with the A/California/04/2009 virus and partial protection against A/PR/8/1934 virus, an antigenically distant human isolate. VLP vaccination induced predominant IgG2a antibody responses, high hemagglutination inhibition (HAI) titers, and recall IgG and IgA antibody responses. HAI titers after VLP vaccination were equivalent to those observed after live virus infection. VLP immune sera also showed HAI responses against diverse geographic pandemic isolates. Notably, a low dose of VLPs could provide protection against lethal infection.Conclusion/SignificanceThis study demonstrates that VLP vaccination provides highly effective protection against the 2009 pandemic influenza virus. The results indicate that VLPs can be developed into an effective vaccine, which can be rapidly produced and avoid the need to isolate high growth reassortants for egg-based production.
Highlights
Influenza is a serious human respiratory disease causing recurrent outbreaks, significantly affecting human health and the global economy
Conclusion/Significance: This study demonstrates that virus-like particles (VLPs) vaccination provides highly effective protection against the 2009 pandemic influenza virus
Characterization of A/California/04/2009 VLPs We produced 2009 swine-origin influenza virus A (SOIV) VLPs in insect cells co-infected with recombinant baculoviruses expressing the M1 matrix and HA glycoprotein derived from A/California/04/ 09 (H1N1) virus following a procedure previously described [17]
Summary
Influenza is a serious human respiratory disease causing recurrent outbreaks, significantly affecting human health and the global economy. In April 2009, several human cases infected with a novel H1N1 swine-origin influenza virus A (SOIV) were reported in Mexico and in the United States [1,2,3,4]. This virus spread rapidly to over 74 countries around the world by early June 2009 when the WHO raised the global outbreak alert level to the pandemic phase 6 [3,5]. The 2009 influenza pandemic and shortages in vaccine supplies worldwide underscore the need for new approaches to develop more effective vaccines
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