Author(s): Yunrui Tan aff1 , Fang He [*] aff1 , Jimmy Kwang [*] aff1 aff2
epitope chimeric; H5N1; influenza; stalked based; subunit vaccine; universal vaccine; viral vector-based vaccine
Currently, efficacy of influenza vaccines mainly relies on the elicitation of highly strain-specific neutralizing antibodies, particularly targeting to HA protein of influenza virus. Most unsatisfying protection by current vaccines against mismatched viruses is caused by the phenomenon of antigenic drift and antigenic shift in the influenza genome. Accumulative amino acid mutations under constant immune pressure by antibody lead to antigenic drift, which results in multiple clades within H5N1 subtype. Meanwhile, antigenic shift refers to genetic reassortment between two or more influenza strains. Inactivated H5N1 whole virus vaccine (IV) is currently the major type available in the market. However, its cross-clade protection is limited. On the basis of data presented by the WHO, sera from ferret that individually immunized with different H5N1 strains were used for hemagglutinin inhibition assay during the vaccine strain selection. As a result, these sera exhibited significant hemagglutinin inhibition (HI) titer only against homologous strain or viruses from same subclades but not the heterologous strains or viruses from different subclades. For example, sera from A/Vietnam1203/2004 (clade 1) immunized ferret showed HI titer of 160 against homologous virus but the HI titers were dramatically reduced to 20 against A/Turkey/15/2005 (clade 2, subclade 2) and 10 against A/Guangxi/1/2005 (clade 2, subclade 3) [ 1 ]. Besides, the production of inactivated vaccines involves egg-based technology which replies on the stable supply of specific-pathogen-free embryonic eggs and poses the risk of allergic reaction in some population. The requirement of high level biocontainment facility is another restriction for vaccine production under this category. These results highlighted the need of a universal H5N1 vaccine which confers protection against different strains of H5N1 [2 ]. Recently, efforts are made in several new strategies for H5N1 vaccines to induce board and persistent immunity against influenza viruses.
Subunit influenza vaccine
Subunit vaccines composed of recombinant proteins expressed in different systems. One of the most common strategies is to express viral proteins in prokaryotic system such as Escherichia coli . Influenza virus M2, NP and HA are the popular choices in subunit vaccine development due to their highly conserved features (M2 and NP) and the immunogenic properties (HA). M2 and NP-based subunit vaccines can only induce cross reactive cytotoxic T-lymphocytes responses. It can only reduce the severity and duration of virus infection but not to prevent infection [ 3 ]. There is a study showed that oligomeric H5 HA1 expressed by Escherichia coli under controlled redox refolding conditions provide cross-clade protection in ferrets against homologous and heterologous challenges from clade 1, clade 2.2, clade 2.3.4 and clade 2.1 influenza viruses [4 ]. Furthermore, Lin et al . also demonstrated mice immunized with baculovirus-expressed soluble trimeric Anhui HA able to produce high level of neutralizing antibodies against H5 viruses when coupling with a PELC/CpG adjuvant. This soluble protein can also be used as a booster following the immunization of inactivated H5 vaccine (NIBRG-14) in order...