Abstract
Development of effective vaccines to prevent influenza, particularly highly pathogenic avian influenza (HPAI) caused by influenza A virus (IAV) subtype H5N1, is a challenging goal. In this study, we designed and constructed two recombinant influenza vaccine candidates by fusing hemagglutinin 1 (HA1) fragment of A/Anhui/1/2005(H5N1) to either Fc of human IgG (HA1-Fc) or foldon plus Fc (HA1-Fdc), and evaluated their immune responses and cross-protection against divergent strains of H5N1 virus. Results showed that these two recombinant vaccines induced strong immune responses in the vaccinated mice, which specifically reacted with HA1 proteins and an inactivated heterologous H5N1 virus. Both proteins were able to cross-neutralize infections by one homologous strain (clade 2.3) and four heterologous strains belonging to clades 0, 1, and 2.2 of H5N1 pseudoviruses as well as three heterologous strains (clades 0, 1, and 2.3.4) of H5N1 live virus. Importantly, immunization with these two vaccine candidates, especially HA1-Fdc, provided complete cross-clade protection against high-dose lethal challenge of different strains of H5N1 virus covering clade 0, 1, and 2.3.4 in the tested mouse model. This study suggests that the recombinant fusion proteins, particularly HA1-Fdc, could be developed into an efficacious universal H5N1 influenza vaccine, providing cross-protection against infections by divergent strains of highly pathogenic H5N1 virus.
Highlights
Influenza epidemics and pandemics caused by influenza A virus (IAV) occur frequently
The proteins were analyzed by SDS-PAGE, followed by Coomassie blue staining, and reactivity was determined using a HA-specific monoclonal antibody developed in our laboratory [29]
The purified recombinant proteins of hemagglutinin 1 (HA1) could be recognized by the HA-specific monoclonal antibody (mAb), as indicated by Western blot (Fig. 2B), revealing their high specificity to the HA of H5N1
Summary
Influenza epidemics and pandemics caused by influenza A virus (IAV) occur frequently. The first influenza pandemic of the 21st century emerged in 2009, with a novel swine-origin influenza virus (S-OIV) H1N1 as the causative agent. Of more concern is the continual outbreak of highly pathogenic avian influenza (HPAI) H5N1, an influenza A subtype virus circulating in poultry, which has caused hundreds of human diseases with severe morbidity and high mortality since its re-emergence in 2003 (http://www.who.int/csr/disease/avian_influenza/country/ cases_table_2010_12_09/en/index.html). Genetic analysis of H5N1 isolated from humans revealed that all genes were of avian origin, limited person-to-person transmission of H5N1 viruses was identified [5]. The concern is that future influenza epidemics may be caused by new virus strains derived from mutations and/or reassortments of existing influenza viruses, HPAI H5N1. The development of effective preventive and therapeutic measures against IAV, avian H5N1, is urgently needed
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