ABSTRACT
Influenza pandemics can spread quickly and cost millions of lives; the 2009 H1N1 pandemic highlighted the shortfall in the current vaccine strategy and the need for an improved global response in terms of shortening the time required to manufacture the vaccine and increasing production capacity. Here we describe the pre-clinical assessment of a novel 2009 H1N1 pandemic influenza vaccine based on the E. coli-produced HA globular head domain covalently linked to virus-like particles derived from the bacteriophage Qß. When formulated with alum adjuvant and used to immunize mice, dose finding studies found that a 10 µg dose of this vaccine (3.7 µg globular HA content) induced antibody titers comparable to a 1.5 µg dose (0.7 µg globular HA content) of the licensed 2009 H1N1 pandemic vaccine Panvax, and significantly reduced viral titers in the lung following challenge with 2009 H1N1 pandemic influenza A/California/07/2009 virus. While Panvax failed to induce marked T cell responses, the novel vaccine stimulated substantial antigen-specific interferon-γ production in splenocytes from immunized mice, alongside enhanced IgG2a antibody production. In ferrets the vaccine elicited neutralizing antibodies, and following challenge with influenza A/California/07/2009 virus reduced morbidity and lowered viral titers in nasal lavages.
Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Influenza A Virus, H1N1 Subtype/immunology , Influenza Vaccines/immunology , Th1 Cells/immunology , Vaccines, Virus-Like Particle/immunology , Adjuvants, Immunologic , Alum Compounds , Animals , Antibody Specificity , Bacteriophages/immunology , Escherichia coli/genetics , Escherichia coli/immunology , Female , Ferrets/immunology , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Humans , Immunoglobulin G/immunology , Interferon-gamma/biosynthesis , Mice , Orthomyxoviridae Infections/prevention & control , RNA, Bacterial/immunology , T-Cell Antigen Receptor Specificity/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Th1 Cells/metabolismABSTRACT
This article discusses the results in Boys and Henderson (2004, Biometrics 60, 573-581) in which the authors propose a new approach to the classification of genomic DNA into a number of hidden Markov states with a variable order of dependency, potentially allowing for the high-throughput detection of structure within genomic DNA. This article is likely to be an important point of departure for further modeling of this type. We question whether the genome of the bacteriophage lambda is the most appropriate example with which to demonstrate the method's effectiveness, whether it can be expected that the method will carry over to genomes where there is only one direction of transcription and no operon structure, and suggest a graphical display that seems to offer insight into the results. It would be interesting to see an analysis that uses the codon alphabet.
