tetano
Editor, Senior Moderator
J Virol
. 2022 Apr 21;e0033222.
doi: 10.1128/jvi.00332-22. Online ahead of print.
Novel Epitopes of the Influenza Virus N1 Neuraminidase Targeted by Human Monoclonal Antibodies
Ericka Kirkpatrick Roubidoux[SUP] 1 2 [/SUP], Kaori Sano[SUP] 1 [/SUP], Meagan McMahon[SUP] 1 [/SUP], Juan Manuel Carreño[SUP] 1 [/SUP], Christina Capuano[SUP] 1 [/SUP], Kaijun Jiang[SUP] 1 [/SUP], Viviana Simon[SUP] 1 3 4 [/SUP], Harm van Bakel[SUP] 5 6 [/SUP], Patrick Wilson[SUP] 7 [/SUP], Florian Krammer[SUP] 1 [/SUP]
Affiliations
Abstract
Influenza virus neuraminidase (NA)-targeting antibodies are an independent correlate of protection against influenza. Antibodies against the NA act by blocking enzymatic activity, preventing virus release and transmission. As we advance the development of improved influenza virus vaccines that incorporate standard amounts of NA antigen, it is important to identify the antigenic targets of human monoclonal antibodies (mAbs). Here, we describe escape mutants generated by serial passage of A/Netherlands/602/2009 (H1N1)pdm09 in the presence of human anti-N1 mAbs. We observed escape mutations on the head domain of the N1 protein around the enzymatic site (S364N, N369T, and R430Q) and also detected escape mutations located on the sides and bottom of the NA (N88D, N270D, and Q313K/R). This work increases our understanding of how human antibody responses target the N1 protein. IMPORTANCE 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.
Keywords: N1; influenza; mAbs; neuraminidase.
. 2022 Apr 21;e0033222.
doi: 10.1128/jvi.00332-22. Online ahead of print.
Novel Epitopes of the Influenza Virus N1 Neuraminidase Targeted by Human Monoclonal Antibodies
Ericka Kirkpatrick Roubidoux[SUP] 1 2 [/SUP], Kaori Sano[SUP] 1 [/SUP], Meagan McMahon[SUP] 1 [/SUP], Juan Manuel Carreño[SUP] 1 [/SUP], Christina Capuano[SUP] 1 [/SUP], Kaijun Jiang[SUP] 1 [/SUP], Viviana Simon[SUP] 1 3 4 [/SUP], Harm van Bakel[SUP] 5 6 [/SUP], Patrick Wilson[SUP] 7 [/SUP], Florian Krammer[SUP] 1 [/SUP]
Affiliations
- PMID: 35446141
- DOI: 10.1128/jvi.00332-22
Abstract
Influenza virus neuraminidase (NA)-targeting antibodies are an independent correlate of protection against influenza. Antibodies against the NA act by blocking enzymatic activity, preventing virus release and transmission. As we advance the development of improved influenza virus vaccines that incorporate standard amounts of NA antigen, it is important to identify the antigenic targets of human monoclonal antibodies (mAbs). Here, we describe escape mutants generated by serial passage of A/Netherlands/602/2009 (H1N1)pdm09 in the presence of human anti-N1 mAbs. We observed escape mutations on the head domain of the N1 protein around the enzymatic site (S364N, N369T, and R430Q) and also detected escape mutations located on the sides and bottom of the NA (N88D, N270D, and Q313K/R). This work increases our understanding of how human antibody responses target the N1 protein. IMPORTANCE 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.
Keywords: N1; influenza; mAbs; neuraminidase.