Broadly Protective Adenovirus-Based Multivalent Vaccines against Highly Pathogenic Avian Influenza Viruses for Pandemic Preparedness

Sai V Vemula,Yadvinder S Ahi,Suryaprakash Sambhara,Anne-Marie Swaim,Suresh K Mittal,Ruben Donis,Jacqueline M Katz,Man-Seong Park

doi:10.1371/journal.pone.0062496

Sai V Vemula, Yadvinder S Ahi + Show 6 more

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https://doi.org/10.1371/journal.pone.0062496

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Abstract

Recurrent outbreaks of H5, H7 and H9 avian influenza viruses in domestic poultry accompanied by their occasional transmission to humans have highlighted the public health threat posed by these viruses. Newer vaccine approaches for pandemic preparedness against these viruses are needed, given the limitations of vaccines currently approved for H5N1 viruses in terms of their production timelines and the ability to induce protective immune responses in the absence of adjuvants. In this study, we evaluated the feasibility of an adenovirus (AdV)-based multivalent vaccine approach for pandemic preparedness against H5, H7 and H9 avian influenza viruses in a mouse model. Replication-defective AdV vectors expressing hemagglutinin (HA) from different subtypes and nucleoprotein (NP) from one subtype induced high levels of humoral and cellular immune responses and conferred protection against virus replication following challenge with H5, H7 and H9 avian influenza virus subtypes. Inclusion of HA from the 2009 H1N1 pandemic virus in the vaccine formulation further broadened the vaccine coverage. Significantly high levels of HA stalk-specific antibodies were observed following immunization with the multivalent vaccine. Inclusion of NP into the multivalent HA vaccine formulation resulted in the induction of CD8 T cell responses. These results suggest that a multivalent vaccine strategy may provide reasonable protection in the event of a pandemic caused by H5, H7, or H9 avian influenza virus before a strain-matched vaccine can be produced.

Highlights

Occasional reports of human infection with both low and highly pathogenic avian influenza A viruses of H5, H7, and H9 subtypes underscore the public health threat and pandemic potential posed by these avian influenza subtypes [1,2]
Ethics Statement The Purdue University Biosafety Committee and Animal Care and Use Committee approved the protocol for all animal studies described in this manuscript and conducted at Purdue University, under the auspices of the Institutional Animal Care and Use Committee (IACUC) #A3231-01 which is supported by the American Association for Laboratory Animal Science (AALAS)
The Institutional Review Boards (IRB) are a unit of the Human Research Protection Program (HRPP) which is housed within the Office of Research Administration (ORA)

Summary

Introduction

Occasional reports of human infection with both low and highly pathogenic avian influenza A viruses of H5, H7, and H9 subtypes underscore the public health threat and pandemic potential posed by these avian influenza subtypes [1,2]. Since their emergence in Asia over a decade ago, highly pathogenic avian influenza H5N1 viruses have spread to over sixty countries on three continents and are endemic among poultry in South East Asia and Africa. The recent 2009 H1N1 pandemic influenza virus possesses genes derived from avian, human and swine influenza viruses through multiple reassortment events [8]

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