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

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.

Development and Evaluation of an Inactivated Influenza A(H5N8) Vaccine

“…NA H5N8+6PR8 vaccination indicated low protection capacity (less than 30%. 19,20 Similarly, the vaccine including both HA and NA (HA, NA H5N8+6PR8 ) segments were protective in our experiments, while the NAH5N8+7PR8 provided only 20% protection.…”

AddaVax-Adjuvanted H5N8 Inactivated Vaccine Induces Robust Humoral Immune Response against Different Clades of H5 Viruses

“…It has been found that the HA of various avian influenza viruses contains multi-basic cleavage sites that are lethal to chickens, such as arginine (R) and lysine (K) sites in H5Nx and H7Nx [ 7 ], and REKRRKR/GLF in H5N8 [ 8 ]. After deleting the polybasic amino acids at the HA cleavage site of the HPAI parent virus, the new modified HA, along with the NA of the wild virus and the six internal segments of the backbone (such as A/PR/8/1934 H1N1 virus) is frequently used to generate a new low pathogenic virus as a vaccine candidate virus by reverse genetics (RG) [ 9 , 10 ].…”