손수민 (한국생명공학연구원) | 한빛사논문 > 한빛사

한빛사논문

조회478

손수민Sumin Son

한국생명공학연구원

Antiviral Res., 2023 May;213:105591 | http://dx.doi.org/10.1016/j.antiviral.2023.105591 Identification of broad-spectrum neutralizing antibodies against influenza A virus and evaluation of their prophylactic efficacy in mice

Sumin Son ^{a 1}, Soo Bin Ahn ^{b c 1}, Geonyeong Kim ^a, Yejin Jang ^b, Chunkyu Ko ^b, Meehyein Kim ^{b c *}, Sang Jick Kim ^{a *}

^aSynthetic Biology and Bioengineering Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea
^bInfectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon, 34114, Republic of Korea
^cGraduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, 34134, Republic of Korea

¹These authors contributed equally to this work and share the first authorship.
*Corresponding author: correspondence to Meehyein Kim or Sang Jick Kim

Abstract

Influenza A virus continuously infects humans and the antigenic shifts of this respiratory virus enable it to cross the species barrier, threatening public health with the risk of pandemics. Broadly neutralizing antibodies (bnAbs) that target the antigenic surface glycoprotein, hemagglutinin (HA), of influenza A virus protect against various subtypes of the virus. Here, we screened a human scFv library, through phage display and panning against recombinant HA proteins, to discover human monoclonal antibodies (mAbs) that are broadly active. Consequently, two human mAbs, named G1 and G2, were identified, which target the HA proteins of the H1N1 and H3N2 subtypes, respectively. G1 was shown to have broad binding ability to different HA subtypes of group 1. By contrast, G2 had higher binding affinity but sensed exclusively H3 subtype-derived HAs. In a cell culture-based virus-neutralizing assay, both G1 and G2 efficiently suppressed infection of the parental influenza A viruses of H1N1 and H3N2 subtypes. Mode-of-action studies showed that the G1 antibody blocked HA2-mediated membrane fusion. Meanwhile, G2 inhibited HA1-mediated viral attachment to host cells. It is noteworthy that both antibodies elicited antibody-dependent cellular cytotoxicity (ADCC) activities by recruiting FcγRIIIA-expressing effector cells. In mouse challenge models, single-shot, intraperitoneal administration of chimeric G1 and G2 antibodies with the mouse IgG constant region completely protected mice from viral infections at doses above 10 and 1 mg/kg, respectively. The newly identified bnAbs, G1 and G2, could provide insight into the development of broad-spectrum antivirals against future pandemic influenza A virus involving group 1- or H3-subtyped strains.

논문정보

형식Research article
게재일2023년 05월 (BRIC 등록일 2023-07-04)
연구진국내 연구진
분야 생명과학 > 생물공학

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