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

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.

The receptor binding domain of SARS-CoV-2 spike protein fused with the type IIbE. coliheat-labile enterotoxin A subunit as an intranasal booster after mRNA vaccination

“…The direct fusion of the CT A1 subunit with influenza A matrix protein 2 (M2e) and an immunoglobulin binding D domain (DD) (CTA1-M2e-DD) has been shown to confer a broad range of protective immunity against homologous and heterologous influenza A viruses (37)(38)(39). We have previously reported that a direct fusion of the type IIb LT A subunit (LTA) with influenza hemagglutinin via intranasal immunization induced both systemic and mucosal immunity against H5N1 infections in mice and chickens (40). In this study, we used the direct fusion of the type IIb LTA with RBD of SARS CoV-2 S protein (RBD-LTA) as an intranasal vaccine candidate and evaluated for its elicitation of systemic and mucosal and systemic immune responses in BALB/c mice and golden hamsters.…”