A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses

Ekiert, D.C.; Friesen, Robert H.; Bhabha, Gira; Kwaks, Ted; Jongeneelen, Mandy; Yu, Wenli; Ophorst, C.; Cox, Freek; Korse, Hans J. W. M.; Brandenburg, Boerries; Vogels, Ronald; Brakenhoff, Just P. J.; Kompier, Ronald; Koldijk, Martin; Cornelissen, Lisette A. H. M.; Poon, Leo L. M.; Peiris, Malik; Koudstaal, Wouter; Wilson, Ian A.; Goudsmit, Jaap

doi:10.1126/science.1204839

Cited by 782 publications

(859 citation statements)

References 39 publications

Supporting

Mentioning

833

Contrasting

Unclassified

Order By: Relevance

“…Viruses undergoing high gene variation will typically silence their broad neutralizing sites when infiltrating the immune system of the host, as exemplified by HIV [22] and Influenza virus [23][24][25]. We next sought to determine the predominance of 8G12-like antibodies in the anti-HEV pools during the immune responses elicited by HEV infection and vaccine inoculation.…”

Section: Mab 8g12 Blocks the Binding Of Naturally Acquired Antibodiesmentioning

confidence: 99%

Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody

Tang

Zhang

et al. 2015

Cell Res

View full text Add to dashboard Cite

Hepatitis E virus (HEV), a non-enveloped, positive-sense, single-stranded RNA virus, is a major cause of enteric hepatitis. Classified into the family Hepeviridae, HEV comprises four genotypes (genotypes 1-4), which belong to a single serotype. We describe a monoclonal antibody (mAb), 8G12, which equally recognizes all four genotypes of HEV, with ~2.53-3.45 nM binding affinity. The mAb 8G12 has a protective, neutralizing capacity, which can significantly block virus infection in host cells. Animal studies with genotypes 1, 3 and 4 confirmed the cross-genotype neutralizing capacity of 8G12 and its effective prevention of hepatitis E disease. The complex crystal structures of 8G12 with the HEV E2s domain (the most protruded region of the virus capsid) of the abundant genotypes 1 and 4 were determined at 4.0 and 2.3 Å resolution, respectively. These structures revealed that 8G12 recognizes both genotypes through the epitopes in the E2s dimerization region. Structure-based mutagenesis and cell-model assays with virus-like particles identified several conserved residues (Glu549, Lys554 and Gly591) that are essential for 8G12 neutralization. Moreover, the epitope of 8G12 is identified as a key epitope involved in virus-host interactions. These findings will help develop a common strategy for the prevention of the most abundant form of HEV infection.

show abstract

Section: Mab 8g12 Blocks the Binding Of Naturally Acquired Antibodiesmentioning

confidence: 99%

Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody

Tang

Zhang

et al. 2015

Cell Res

View full text Add to dashboard Cite

show abstract

“…Antibodies directed against the globular domain of HA, as well as the highly conserved stem region, efficiently neutralize the virus. The identification of broadly neutralizing antibodies that target highly conserved stem epitopes offers the exciting prospect of designing universal or pan-influenza vaccines that can protect against IAV expressing several or all subtypes of HA (10,(15)(16)(17)(18)(19)(20).…”

mentioning

confidence: 99%

Structure and accessibility of HA trimers on intact 2009 H1N1 pandemic influenza virus to stem region-specific neutralizing antibodies

Harris

Meyerson

Matsuoka³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

101

113

View full text Add to dashboard Cite

Rapid antigenic variation of HA, the major virion surface protein of influenza A virus, remains the principal challenge to the development of broader and more effective vaccines. Some regions of HA, such as the stem region proximal to the viral membrane, are nevertheless highly conserved across strains and among most subtypes. A fundamental question in vaccine design is the extent to which HA stem regions on the surface of the virus are accessible to broadly neutralizing antibodies. Here we report 3D structures derived from cryoelectron tomography of HA on intact 2009 H1N1 pandemic virions in the presence and absence of the antibody C179, which neutralizes viruses expressing a broad range of HA subtypes, including H1, H2, H5, H6, and H9. By fitting previously derived crystallographic structures of trimeric HA into the density maps, we deduced the locations of the molecular surfaces of HA involved in interaction with C179. Using computational methods to distinguish individual unliganded HA trimers from those that have bound C179 antibody, we demonstrate that ∼75% of HA trimers on the surface of the virus have C179 bound to the stem domain. Thus, despite their close packing on the viral membrane, the majority of HA trimers on intact virions are available to bind anti-stem antibodies that target conserved HA epitopes, establishing the feasibility of universal influenza vaccines that elicit such antibodies.envelope glycoproteins | subvolume averaging | virus structure | hemagglutunin | cryo-electron microscopy

show abstract

“…Différentes équipes de recherche, dont la nôtre, ont récemment décrit des anticorps monoclonaux humains capables de neutraliser différents sous-types du groupe 1 et/ou du groupe 2 des virus influenza A (Figure 1) [2,[4][5][6]8]. Jusqu'à aujourd'hui, moins d'attention avait été portée aux virus influenza B, probablement parce qu'ils n'infectent pas les oiseaux aquatiques, réservoir clé pour l'émergence des pandémies.…”

Section: Anticorps Neutralisant Le Virus Grippalunclassified

“…Les virus influenza B ne ségrègent pas en sous-types, mais leur évolution est caractérisée par la cocirculation de deux lignées possé-dant des caractéristiques génétiques et antigéniques différentes ( Figure 1B) [7]. L'HA, une glycoprotéine antigé-nique présente à la surface du virus de la grippe, est nécessaire à l'atta-A (bnAb, broadly neutralizing antibodies) [2][3][4][5][6] [2,4,6]. Cette région hautement conservée se situe au niveau de la partie de l'HA proche de la membrane appelée stem 1 (Figure 3).…”

Section: L'hémagglutinine : Cible Des Anticorps Neutralisantsunclassified

Vers un vaccin universel contre la grippe ?

Dreyfus

2013

Med Sci (Paris)

View full text Add to dashboard Cite

A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses

Cited by 782 publications

References 39 publications

Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody

Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody

Structure and accessibility of HA trimers on intact 2009 H1N1 pandemic influenza virus to stem region-specific neutralizing antibodies

Vers un vaccin universel contre la grippe ?

Contact Info

Product

Resources

About