Highly Pathogenic Avian Influenza H5 Hemagglutinin Fused with the A Subunit of Type IIb Escherichia coli Heat Labile Enterotoxin Elicited Protective Immunity and Neutralization by Intranasal Immunization in Mouse and Chicken Models.

Neos Tang,Shi-Wei Lin,Ting-Hsuan Chen,Suh-Chin Wu,Jia-Tsrong Jan,Hung-Yi Wu

doi:10.3390/vaccines7040193

Abstract

Highly pathogenic avian influenza viruses are classified by the World Organization for Animal Health (OIE) as causes of devastating avian diseases. This study aimed to develop type IIb Escherichia coli heat-labile enterotoxin (LTIIb) as novel mucosal adjuvants for mucosal vaccine development. The fusion protein of H5 and LTIIb-A subunit was expressed and purified for mouse and chicken intranasal immunizations. Intranasal immunization with the H5-LTIIb-A fusion protein in mice elicited potent neutralizing antibodies in sera and bronchoalveolar lavage fluids, induced stronger Th1 and Th17 cellular responses in spleen and cervical lymph nodes, and improved protection against H5N1 influenza virus challenge. More interestingly, intranasal immunization with the H5-LTIIb-A fusion protein in chickens elicited high titers of IgY, IgA, hemagglutinin inhibition (HAI), and neutralizing antibodies in their antisera. This study employed the novel adjuvants of LTIIb for the development of a new generation of mucosal vaccines against highly pathogenic avian influenza viruses.

Highlights

Influenza A virus is a member of the Orthomyxoviridae family and causes several pandemic infections, such as 1918 H1N1 (Spanish flu), 1957 H2N2 (Asian flu), 1968 H3N2 (Hong Kong flu), 1977H1N1 (Russian flu), and 2009 H1N1 pandemics [1]
Because the AB5 structure of LTIIb is composed of the A subunit (LTIIb-A) and the pentameic B subunits (LTIIb-B5) [9], the B subunit was considered as a non-toxic and more safer mucosal adjuvant [21]
The sequence of the H5-LTIIb-A fusion protein, which consisted of an H5 ectodomain, a full-length

Summary

Introduction

Influenza A virus is a member of the Orthomyxoviridae family and causes several pandemic infections, such as 1918 H1N1 (Spanish flu), 1957 H2N2 (Asian flu), 1968 H3N2 (Hong Kong flu), 1977H1N1 (Russian flu), and 2009 H1N1 pandemics [1]. Influenza A virus is a member of the Orthomyxoviridae family and causes several pandemic infections, such as 1918 H1N1 (Spanish flu), 1957 H2N2 (Asian flu), 1968 H3N2 (Hong Kong flu), 1977. Pathogenic avian influenza (HPAI) H5N1 viruses can cause serious infection in humans. Infection with HPAI H5N1 results from contact with infected avians; these viruses cannot be transmitted efficiently among humans. HPAI H5N1 viruses mainly infect the lower respiratory tracts and result in lung damage and plasma cytokine dysregulation [2,3]. In 1997, the first case of human infection with HPAI H5N1 virus occurred in. Hong Kong; the virus re-emerged in 2003, and since human infections caused by it have been continuously reported in Asia, the Middle East, Europe, and Africa, with an approximately 60%. Mortality rate [1,4,5,6].

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