Abstract
Influenza viruses cause annual epidemics and occasional pandemics. The high diversity of viral envelope proteins permits viruses to escape host immunity. Therefore, the development of a universal vaccine and broadly neutralizing antibodies (bnAbs) is essential for controlling various mutant viruses. Here, we review some potentially valuable bnAbs for influenza; one is a novel passive immunotherapy using a variable domain of heavy chain-only antibody (VHH), and the other is polymeric immunoglobulin A (pIgA) induced by intranasal vaccination. Recently, it was reported that a tetravalent multidomain antibody (MDAb) was developed by genetic fusion of four VHHs, which are bnAbs against the influenza A or B viruses. The transfer of a gene encoding the MDAb–Fc fusion protein provided cross-protection against both influenza A and B viruses in vivo. An intranasal universal influenza vaccine, which can induce neutralizing pIgAs in the upper respiratory tract, is currently undergoing clinical studies. A recent study has revealed that tetrameric IgAs formed in nasal mucosa are more broadly protective against influenza than the monomeric and dimeric forms. These broadly neutralizing antibodies have high potential to control the currently circulating influenza virus.
Highlights
Cross protection against infectious diseases is extremely important due to the existence of multiple virus subtypes
It is well known that influenza viruses invade the respiratory tract, where polymeric IgAs, which play a key protective role against the virus, are produced [9]
One study indicated that passive immunization via intranasal delivery of an associated virus (AAV) vector encoding broadly neutralizing mAbs (bnAbs) FI6 could broadly protect against influenza virus infections [93]
Summary
Cross protection against infectious diseases is extremely important due to the existence of multiple virus subtypes. The development of a universal vaccine or broadly neutralizing mAbs (bnAbs) is important to assist with the control of viral infections. We review how cross-protection can be achieved, via passive immunotherapy or vaccination, against influenza, a representative viral infection. Several bnAbs against the influenza virus that produce cross-protection have been isolated [7]. Current passive immunotherapy using MDAbs may provide broad protection against numerous virus infections. It is well known that influenza viruses invade the respiratory tract, where polymeric IgAs (pIgAs), which play a key protective role against the virus, are produced [9]. We focus on intranasal vaccines that induce pIgA generation in the upper respiratory mucosa and protect against influenza virus infection [9,10]. It was revealed that tetrameric IgA has better neutralizing activity than monomeric or dimeric IgAs [11]
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