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J Virol. 2014 Apr 2. [Epub ahead of print]
A broadly neutralizing human monoclonal antibody directed against a novel conserved epitope on the influenza virus H3 hemagglutinin globular head.
Benjamin E1, Wang W, McAuliffe J, Palmer-Hill F, Kallewaard N, Chen Z, Suzich J, Blair W, Jin H, Zhu Q.
Author information
Abstract
Most neutralizing antibodies elicited during influenza infection or vaccination target immunodominant, variable epitopes on the globular head region of hemagglutinin (HA), which leads to narrow strain protection. In this study, we describe the properties of a unique anti-HA monoclonal antibody, D1-8, that was derived from human B-cells and exhibits potent, broad neutralizing activity across antigenically diverse influenza H3 subtype viruses. Based on selection of escape variants, we show that D1-8 targets a novel epitope on the globular head region of the influenza HA protein. The HA residues implicated in D1-8 binding are highly conserved among H3N2 viruses, and are located proximal to antigenic site D, We demonstrate that the potent in vitro antiviral activity of D1-8 translates into protective activity in mouse models of influenza infection. Furthermore, D1-8 exhibits superior therapeutic survival benefit in influenza infected mice compared to the neuraminidase inhibitor, oseltamivir, when treatment is started late in infection. The present study suggests the potential application of this monoclonal antibody for the therapeutic treatment of H3N2 influenza infection.
IMPORTANCE:
Recently a few globular head targeting mAbs have been discovered that exhibit activity against different subtypes of influenza subtypes, such as H1; however, none of the previously described mAbs showed broadly neutralizing activity against diverse H3 viruses. In this study, we describe a human mAb, D1-8, that exhibits potent, broad neutralizing activity against antigenically diverse H3 subtype viruses. The genotypic analysis of escape mutants revealed a unique putative epitope region in the globular head of H3 HA that is comprised of highly conserved residues and is distinct from the receptor binding site. Furthermore, we demonstrate that D1-8 exhibits superior therapeutic efficacy in influenza infected mice compared to the neuraminidase inhibitor, oseltamivir, when treatment is started late in infection. In addition to describing a novel anti-globular head of H3 HA mAb with potent broadly neutralizing activity, our study suggests the potential of D1-8 for therapeutic treatment of seasonal influenza H3 infection.
PMID:
24696468
[PubMed - as supplied by publisher]
A broadly neutralizing human monoclonal antibody directed against a novel conserved epitope on the influenza virus H3 hemagglutinin globular head.
Benjamin E1, Wang W, McAuliffe J, Palmer-Hill F, Kallewaard N, Chen Z, Suzich J, Blair W, Jin H, Zhu Q.
Author information
Abstract
Most neutralizing antibodies elicited during influenza infection or vaccination target immunodominant, variable epitopes on the globular head region of hemagglutinin (HA), which leads to narrow strain protection. In this study, we describe the properties of a unique anti-HA monoclonal antibody, D1-8, that was derived from human B-cells and exhibits potent, broad neutralizing activity across antigenically diverse influenza H3 subtype viruses. Based on selection of escape variants, we show that D1-8 targets a novel epitope on the globular head region of the influenza HA protein. The HA residues implicated in D1-8 binding are highly conserved among H3N2 viruses, and are located proximal to antigenic site D, We demonstrate that the potent in vitro antiviral activity of D1-8 translates into protective activity in mouse models of influenza infection. Furthermore, D1-8 exhibits superior therapeutic survival benefit in influenza infected mice compared to the neuraminidase inhibitor, oseltamivir, when treatment is started late in infection. The present study suggests the potential application of this monoclonal antibody for the therapeutic treatment of H3N2 influenza infection.
IMPORTANCE:
Recently a few globular head targeting mAbs have been discovered that exhibit activity against different subtypes of influenza subtypes, such as H1; however, none of the previously described mAbs showed broadly neutralizing activity against diverse H3 viruses. In this study, we describe a human mAb, D1-8, that exhibits potent, broad neutralizing activity against antigenically diverse H3 subtype viruses. The genotypic analysis of escape mutants revealed a unique putative epitope region in the globular head of H3 HA that is comprised of highly conserved residues and is distinct from the receptor binding site. Furthermore, we demonstrate that D1-8 exhibits superior therapeutic efficacy in influenza infected mice compared to the neuraminidase inhibitor, oseltamivir, when treatment is started late in infection. In addition to describing a novel anti-globular head of H3 HA mAb with potent broadly neutralizing activity, our study suggests the potential of D1-8 for therapeutic treatment of seasonal influenza H3 infection.
PMID:
24696468
[PubMed - as supplied by publisher]
