Novel Epitopes of the Influenza Virus N1 Neuraminidase Targeted by Human Monoclonal Antibodies

Abstract

As improved influenza virus vaccines are being developed, the influenza virus neuraminidase (NA) is becoming an important new target for immune responses. By identifying novel epitopes of anti-NA antibodies, we can improve vaccine design. Additionally, characterizing escape mutations in these epitopes aids in identifying NA antigenic drift in circulating viruses.

Monoclonal antibodies targeting the influenza virus N6 neuraminidase

“…To learn more about the epitopes of the generated mAbs, we generated escape mutant viruses (EMVs) by subjecting A/duck/Czechoslovakia/1956 to increasing antibody pressure by passaging the virus with increasing amounts of antibody as described before ( 20 , 21 ). An irrelevant mAb directed against the Lassa virus glycoprotein was included as control ( 53 ).…”

“…This focus on one patch of the NA surface may be a consequence of our immunization regimen or may be specific to the N6 NA. While a similar area is also targeted by N1, N2 and B NA directed antibodies, many other sites, including the enzymatic site, are targeted for these subtypes as well (9,11,13,14,(16)(17)(18)(19)(20)(21). Interestingly, the six mapped antibodies, which focus on the lateral surface show very different activities in vivo ranging from complete protection from weight loss to partial protection from mortality.…”

“…NA-based immunity has been described as infection-permissive but can protect from disease and has been established as independent correlate of protection in humans (7,8). Despite increased efforts to better understand NA antigenicity of human seasonal N1, N2 and type B NAs (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) for the design of improved influenza virus vaccines, little work has been done on non-human NA subtypes (group 1: N1, N4, N5, N8; group 2: N2, N3, N6, N7, N9), and most work has focused almost exclusively on the N9 NA (22)(23)(24)(25)(26)(27).…”

Imprinted Anti-Hemagglutinin and Anti-Neuraminidase Antibody Responses after Childhood Infections of A(H1N1) and A(H1N1)pdm09 Influenza Viruses

“…This also coincides with the observation that most of our study subjects possess ≥1:40 NI titers against more than one antigenically different NA protein. The broader breadth of NI responses can be supported by the conserved epitopes (N273 and N309) mapped by Chen et al ( 26 ) using human MAbs that cross-react with A(H1N1) and A(H1N1)pdm09 viruses from 1918 to 2017, although escape mutants have been selected with these cross-reactive MAbs in vitro ( 27 ). Wan et al ( 28 ) recognized mouse Mab-binding epitopes (group B MAbs identifying residues 273, 338, and 339) that were conserved across NAs of A(H1N1) and A(H1N1)pdm09 viruses from 1918 to 2009.…”

Immune response in influenza virus infection and modulation of immune injury by viral neuraminidase

“…Anti-NA antibodies are less dependent on the HA due to receptor binding for helping aid in the control of viruses [ 122 – 124 ]. Improving vaccine design for identifying NA antigenic drift and novel epitopes of anti-NA antibodies [ 125 ]. Moreover, the Chinese medicinal herb and compound could inhibit the influenza virus by targeting NA [ 109 , 126 , 127 ].…”