Abstract
Highly pathogenic avian influenza virus (HPAIV) subtype H5N1 causes a devastating disease in poultry. Vaccination is an effective method of controlling avian influenza virus (AIV) infection in poultry. The hemagglutinin (HA) protein is the major determinant recognized by the immune system of the host. Cleavage of the HA precursor HA0 into HA1 and HA2 subunits is required for infectivity of the AIV. We evaluated the individual contributions of HA1 and HA2 subunits to the induction of HPAIV serum neutralizing antibodies and protective immunity in chickens. Using reverse genetics, recombinant Newcastle disease viruses (rNDVs) were generated, each expressing HA1, HA2, or HA protein of H5N1 HPAIV. Chickens were immunized with rNDVs expressing HA1, HA2, or HA. Immunization with HA induced high titers of serum neutralizing antibodies and prevented death following challenge. Immunization with HA1 or HA2 alone neither induced serum neutralizing antibodies nor prevented death following challenge. Our results suggest that interaction of HA1 and HA2 subunits is necessary for the display of epitopes on HA protein involved in the induction of neutralizing antibodies and protection. These epitopes are lost when the two subunits are separated. Therefore, vaccination with either a HA1 or HA2 subunit may not provide protection against HPAIV.
Highlights
Avian influenza (AI) is a serious disease in poultry
Infectious recombinant Newcastle disease viruses (rNDVs) containing the HA1 subunit, HA1 subunit fused with Newcastle disease virus (NDV)-F TM and CT domains, the HA2 subunit, and the HA gene of Highly pathogenic avian influenza virus (HPAIV) were recovered from all cDNAs by reverse genetics technique using HEp-2 cells
HA1 fused with NDV F TM and CT domains, HA2 and HA proteins were expressed at a high level on the surface of DF1 cells, whereas HA1 alone was not expressed on the cells’ surface (Figure 2C)
Summary
Avian influenza (AI) is a serious disease in poultry. Avian influenza virus (AIV) belongs to the genus Alphainfluenzavirus in the family Orthomyxoviridae (International Committee on Taxonomy of Viruses [ICTV], 2018). Avian influenza viruses are divided into subtypes based on antigenic differences in the two major surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA) (Palese and Shaw, 2013). 16 HA subtypes (H1–H16) and 11 NA subtypes (N1–N11) in different combinations have been found in avian populations. Avian influenza viruses are classified into highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) viruses. Pathogenic avian influenza viruses in poultry are of H5 and H7 subtypes (Palese and Shaw, 2013; OIE, 2018b). In recent years, H5, H7, H9, and H10 subtypes of AIVs have caused
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