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Viruses 2017, 9(8), 234; doi:10.3390/v9080234

An Adenovirus-Vectored Influenza Vaccine Induces Durable Cross-Protective Hemagglutinin Stalk Antibody Responses in Mice

Viral Immunology Laboratory, International Vaccine Institute, SNU Research Park, 1-Gwanak-ro, Gwanak-gu, Seoul 08826, Korea
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Author to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 10 July 2017 / Revised: 8 August 2017 / Accepted: 14 August 2017 / Published: 21 August 2017
(This article belongs to the Section Antivirals & Vaccines)
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Abstract

Currently licensed vaccines against the influenza A virus (IAV) need to be updated annually to match the constantly evolving antigenicity of the influenza virus glycoproteins, hemagglutinin (HA), and neuramidiase (NA). Attempts to develop universal vaccines that provide broad protection have resulted in some success. Herein, we have shown that a replication-deficient adenovirus expressing H5/M2e induced significant humoral immunity against the conserved HA stalk. Compared to the humoral responses induced by an inactivated influenza vaccine, the humoral responses induced by the adenovirus-vectored vaccine against the conserved stalk domain mediated cross-protection against heterosubtypic influenza viruses. Importantly, virus inactivation by formaldehyde significantly reduced the binding of monoclonal antibodies (mAbs) to the conserved nucleoprotein (NP), M2e, and HA stalk. These results suggest that inactivation by formaldehyde significantly alters the antigenicity of the HA stalk, and suggest that the conformation of the intact HA stalk provided by vector-based vaccines is important for induction of HA stalk-binding Abs. Our study provides insight into the mechanism by which a vector-based vaccine induces broad protection by stimulation of cross-protective Abs targeting conserved domains of viral proteins. The findings support further strategies to develop a vectored vaccine as a universal influenza vaccine for the control of influenza epidemics and unpredicted pandemics. View Full-Text
Keywords: influenza virus; vectored vaccine; cross-protection; stalk immunity; antibody; cytokine influenza virus; vectored vaccine; cross-protection; stalk immunity; antibody; cytokine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Kim, E.H.; Han, G.-Y.; Nguyen, H. An Adenovirus-Vectored Influenza Vaccine Induces Durable Cross-Protective Hemagglutinin Stalk Antibody Responses in Mice. Viruses 2017, 9, 234.

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