Impact of Individual Viral Gene Segments from Influenza A/H5N8 Virus on the Protective Efficacy of Inactivated Subtype-Specific Influenza Vaccine

Yassmin Moatasim,Ghazi Kayali,Mohamed El Sayes,Ahmed Mostafa,Ahmed Kandeil,Maha Alkhazindar,Rabeh El-Shesheny,Mohamed A Ali,Ahmed N El Taweel,Omnia Kutkat,Elsayed T Abdelsalam

doi:10.3390/pathogens10030368

Abstract

Since its emergence in 2014, the highly pathogenic avian influenza H5N8 virus has continuously and rapidly spread worldwide in the poultry sector resulting in huge economic losses. A typical inactivated H5N8 vaccine is prepared using the six internal genes from A/PR8/1934 (H1N1) and the two major antigenic proteins (HA and NA) from the circulating H5N8 strain with the HA modified to a low pathogenic form (PR8HA/NA-H5N8). The contribution of the other internal proteins from H5N8, either individually or in combination, to the overall protective efficacy of PR8-based H5N8 vaccine has not been investigated. Using reverse genetics, a set of PR8-based vaccines expressing the individual proteins from an H5N8 strain were rescued and compared to the parent PR8 and low pathogenic H5N8 strains and the commonly used PR8HA/NA-H5N8. Except for the PR8-based vaccine strains expressing the HA of H5N8, none of the rescued combinations could efficiently elicit virus-neutralizing antibodies. Compared to PR8, the non-HA viral proteins provided some protection to infected chickens six days post infection. We assume that this late protection was related to cell-based immunity rather than antibody-mediated immunity. This may explain the slight advantage of using full low pathogenic H5N8 instead of PR8HA/NA-H5N8 to improve protection by both the innate and the humoral arms of the immune system.

Highlights

H5 highly pathogenic avian influenza (HPAI) viruses were first detected in 1996, and a year later the first human infection case was recorded in Hong Kong as a result of the reassortment of H5N1 with H9N2 low pathogenic avian influenza (LPAI)
H5N8, a set of PR8-based vaccines expressing the individual segments from an H5N8 strain were rescued and compared to the parent PR8 and LP H5N8 strains and the commonly used PR8HA/NA-H5N8 (Figure 1)
Despite that the PB2 of H5N8 was successfully cloned, confirmed by sequencing, and that the LP H5N8 virus was successfully rescued by reverse genetics, the vaccine form of (PB2 H5N8 + 7PR8) was not rescued after several trials which could be explained by genetic incompatibility

Summary

Introduction

Influenza A viruses are differentiated into high pathogenic (HP) or low pathogenic (LP) viruses [1]. H5 highly pathogenic avian influenza (HPAI) viruses were first detected in 1996, and a year later the first human infection case was recorded in Hong Kong as a result of the reassortment of H5N1 with H9N2 low pathogenic avian influenza (LPAI). Virus [2,3]. HPAI H5 viruses became widespread and evolved into several clades. After the 2003 outbreak, clade 2 emerged and further expanded and started to form new H5Nx reassortments. The unified classification of the hemagglutinin (HA) of H5Nx viruses has been designated as clade 2.3.4.4 by the WHO/FAO/OIE H5 Evolution Working

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