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Currently, influenza vaccines are produced using embryonated chicken eggs. Recently, recombinant influenza vaccines have been developed as a potential alternative to egg-grown vaccines. In this study, we evaluated the efficacy of soluble recombinant hemagglutinin (HA) protein produced in human cell culture (Expi293F cells) as an influenza vaccine against homosubtypic and heterosubtypic influenza virus challenges in mice. Mice were immunized intramuscularly with purified soluble HA protein of H1N1pdm09 virus and then challenged with a lethal dose of H1N1pdm09, seasonal H3N2, or highly pathogenic avian influenza (HPAI) H5N1 virus. Vaccinated mice showed better morbidity than mock-vaccinated mice following H1N1pdm09 challenge. By contrast, all mice died following H3N2 challenge. Interestingly, all vaccinated mice survived challenge with H5N1 virus, whereas all mock-vaccinated mice died. These results suggest that intramuscular immunization with recombinant HA proteins produced in Expi 293F cells could be of value in influenza vaccine strategies. [ABSTRACT FROM AUTHOR]

Abstract: Avian influenza A viruses (IAVs) and human 1918, 1957, and 1968 pandemic IAVs all have neuraminidases (NAs) that are stable at low pH sialidase activity, yet most human epidemic IAVs do not. We examined the pH stability of H5N1 highly pathogenic avian IAV (HPAI) NAs and identified amino acids responsible for conferring stability at low pH. We found that, unlike other avian viruses, most H5N1 IAVs isolated since 2003 had NAs that were unstable at low pH, similar to human epidemic IAVs. These H5N1 viruses are thus already human virus-like and, therefore, have the frequent infections of humans. [Copyright &y& Elsevier]

Abstract: To identify a determinant of human H3 hemagglutinin (HA) amino acid residues linked to the recognition of molecular species of sialic acid, we generated six mutant viruses possessing either the wild-type HA gene from A/Memphis/1/71 (H3N2) or a genetically single-mutated HA gene at position 137, 144, 155, 158 or 193 from a genetic backbone of A/WSN/33 (H1N1) by reverse genetics. We evaluated the binding ability with four types of synthetic sialylglycolipids. The results indicate that the amino acid substitutions Thr155 to Tyr and Glu158 to Gly in H3 HA facilitate virus binding to N-glycolylneuraminic acid. [Copyright &y& Elsevier]

Influenza A viruses cause pandemics at random intervals. Pandemics are caused by viruses that contain a hemagglutinin (HA) surface glycoprotein to which human populations are immunologically naive. Such an HA can be introduced into the human population through reassortment between human and avian virus strains or through the direct transfer of an avian influenza virus to humans. The factors that determine the interspecies transmission and pathogenicity of influenza viruses are still poorly understood; however, the HA protein plays an important role in overcoming the interspecies barrier and in virulence in avian influenza viruses. Recently, the RNA polymerase (PB2) protein has also been recognized as a critical factor in host range restriction, while the nonstructural (NS1) protein affects the initial host immune responses. We summarize current knowledge of viral factors that determine host range restriction and pathogenicity of influenza A viruses. [ABSTRACT FROM AUTHOR]

Many cases of human infection with the H7N9 virus have been detected in China since 2013. H7N9 viruses are maintained in chickens and are transmitted to humans at live bird markets. During circulation in birds, H7N9 viruses have accumulated amino acid substitutions in their hemagglutinin (HA), which resulted in an antigenically change in the recent H7N9 viruses. Here, we characterized 46 mouse monoclonal antibodies against the HA of the prototype strain. 16 H7-HA-specific monoclonal antibodies (mAbs) possessed hemagglutination inhibition (HI) and neutralization activities by recognizing the major antigenic site A; four other H7-HA-specific clones also showed HI and neutralizing activities via recognition of the major antigenic sites A and D; seven mAbs that reacted with several HA subtypes and possibly recognized the HA stem partially protected mice from lethal infection with prototype H7N9 virus; and the remaining 19 mAbs had neither HI nor neutralization activity. All human H7N9 viruses tested showed a similar neutralization sensitivity to the first group of 16 mAbs, whereas human H7N9 viruses isolated in 2016–2017 were not neutralized by a second group of 4 mAbs. These results suggest that amino acid substitutions at the epitope of the second mAb group appear to be involved in the antigenic drift of the H7N9 viruses. Further analysis is required to fully understand the antigenic change in H7N9 viruses. [ABSTRACT FROM AUTHOR]

The author discusses the need to further research on transmissible avian flu viruses in order to prevent future pandemics. He mentions that they generated viruses that combined the H5 haemagglutinin (HA) gene with the remaining genes from a pandemic 2009 H1N1 influenza virus. He asserts that results have shown that not all transmissible H5 HA-possessing viruses are lethal.