Broadly Neutralizing Antibodies for Influenza: Passive Immunotherapy and Intranasal Vaccination

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.

Chimeric HP-PRRSV2 containing an ORF2-6 consensus sequence induces antibodies with broadly neutralizing activity and confers cross protection against virulent NADC30-like isolate

“…In addition, the recognition of different neutralizing epitopes may induce homologous nAbs, heterologous nAbs or even broad nAbs (bnAbs) [ 13 , 16 , 17 ]. Similar results have been described in viruses such as human immunodeficiency virus (HIV) and influenza virus [ 18 , 19 ]. PRRSV bnAbs have been found in sera from both naturally or experimentally infected pigs [ 12 , 13 ].…”

A Novel Gene Delivery Vector of Agonistic Anti-Radioprotective 105 Expressed on Cell Membranes Shows Adjuvant Effect for DNA Immunization Against Influenza

“…Seasonal influenza continues to be a major health concern because the influenza virus causes annual epidemics and occasional pandemics around the world. Conventional vaccines do not provide complete protection because of antigenic drift and antigenic shift, mainly caused by membrane proteins such as HA, permitting the virus to escape host immunity ( 27 ). To control circulating influenza viruses, the development of another vaccine, which can induce potent and broad protection against the virus, is indispensable.…”

A Small Virus to Deliver Small Antibodies: New Targeted Therapies Based on AAV Delivery of Nanobodies

“…In this regard, AAV vectors encoding conventional bnAbs have been tested in preclinical studies with promising results [ 116 , 117 , 118 ]. However, the bnAbs described to datelack of sufficient influenza A and B cross-reactivity, which means that a combination of at least two different bnAbs should be used to achieve full protection [ 119 ]. This could represent a problem when using AAV vectors due to its limited packaging capacity (<5 kb).…”