Abstract
The highly pathogenic avian influenza (HPAI) H5N1 virus remains to be one of the world’s largest pandemic threats due to the emergence of new variants. The rapid evolution of new sub-lineages is currently the greatest challenge in vaccine development. In this study, we developed an epitope modified non-pathogenic H5N3 (A/duck/Singapore/97) vaccine for broad protection against influenza H5 subtype. H5N3 hemagglutinin (HA) mutant reassortant viruses with A/Puerto Rico/8/34 (PR8) backbone were generated by mutating amino acids at the 140th loop and 190th α-helix of hemagglutinin. The cross-neutralizing efficacy of reverse genetics-derived H5N3HA (RG-H5N3HA) mutants was confirmed by testing reactivity with reference chicken anti-H5N1 clade 2 virus sera. Furthermore, RG-H5N3HA mutant immunized mice induced cross-neutralizing antibodies and cross-protection against distinct H5N1 viral infection. Our findings suggest that the use of non-pathogenic H5 viruses antigenically related to HPAI-H5N1 allows for the development of broadly protective vaccines and reduces the need for biosafety level 3 (BSL3) containment facilities.
Highlights
Our findings suggest that the use of non-pathogenic H5 viruses antigenically related to Highly pathogenic avian influenza (HPAI)-H5N1 allows for the development of broadly protective vaccines and reduces the need for biosafety level 3 (BSL3) containment facilities
Pathogenic avian influenza (HPAI) H5 subtype viruses cause serious outbreaks among chickens resulting in major economic losses in the poultry industry [1]
To broaden the cross protective efficacy of the non-pathogenic H5N3 vaccine candidate, we modified amino acids of major neutralizing epitopes in the 140th loop and 190th α-helix region of HA which have previously been noted as very important determinants of protective immunity to clade-specific influenza H5N1 [7]
Summary
Pathogenic avian influenza (HPAI) H5 subtype viruses cause serious outbreaks among chickens resulting in major economic losses in the poultry industry [1]. The antigenic site of this non-pathogenic H5 vaccine strain does not match most H5N1 strains, especially that of clade 2 and its sub-lineages, which are known to predominantly circulate and cause human infections [9] In this present study, we modified the antigenic site by mutating amino acids in the 140th loop and the 190th α-helix of the HA of H5N3 (A/duck/Singapore/97) vaccine strain, which are located near the receptor binding site [7] and contribute to the strain-specific antigenic profile of the H5 viruses [10]. These modified HA were used to generate H5N3/PR8 reassortant virus which were evaluated their neutralizing efficacy against H5N1 variants in a mouse model
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