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TitleAnti-idiotype isolation of a broad and potent influenza A virus-neutralizing human antibody.
Journal, issue, pagesFront Immunol, Vol. 15, Page 1399960, Year 2024
Publish dateMay 30, 2024
AuthorsAdam S Olia / Madhu Prabhakaran / Darcy R Harris / Crystal Sao-Fong Cheung / Rebecca A Gillespie / Jason Gorman / Abigayle Hoover / Nicholas C Morano / Amine Ourahmane / Abhinaya Srikanth / Shuishu Wang / Weiwei Wu / Tongqing Zhou / Sarah F Andrews / Masaru Kanekiyo / Lawrence Shapiro / Adrian B McDermott / Peter D Kwong /
PubMed AbstractThe VH6-1 class of antibodies includes some of the broadest and most potent antibodies that neutralize influenza A virus. Here, we elicit and isolate anti-idiotype antibodies against germline ...The VH6-1 class of antibodies includes some of the broadest and most potent antibodies that neutralize influenza A virus. Here, we elicit and isolate anti-idiotype antibodies against germline versions of VH6-1 antibodies, use these to sort human leukocytes, and isolate a new VH6-1-class member, antibody L5A7, which potently neutralized diverse group 1 and group 2 influenza A strains. While its heavy chain derived from the canonical IGHV6-1 heavy chain gene used by the class, L5A7 utilized a light chain gene, IGKV1-9, which had not been previously observed in other VH6-1-class antibodies. The cryo-EM structure of L5A7 in complex with Indonesia 2005 hemagglutinin revealed a nearly identical binding mode to other VH6-1-class members. The structure of L5A7 bound to the isolating anti-idiotype antibody, 28H6E11, revealed a shared surface for binding anti-idiotype and hemagglutinin that included two critical L5A7 regions: an FG motif in the third heavy chain-complementary determining region (CDR H3) and the CDR L1 loop. Surprisingly, the chemistries of L5A7 interactions with hemagglutinin and with anti-idiotype were substantially different. Overall, we demonstrate anti-idiotype-based isolation of a broad and potent influenza A virus-neutralizing antibody, revealing that anti-idiotypic selection of antibodies can involve features other than chemical mimicry of the target antigen.
External linksFront Immunol / PubMed:38873606 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.78 - 3.95 Å
Structure data

43529

8vue

EMDB-43529, PDB-8vue:
L5A7 Fab bound to Indonesia2005 Hemagglutinin
Method: EM (single particle) / Resolution: 3.59 Å

43545

8vuz

EMDB-43545, PDB-8vuz:
L5A7 Fab bound to 28H6E11 anti-idiotype Fab
Method: EM (single particle) / Resolution: 3.95 Å

PDB-8vvb:
Influenza antibody L5A7 Fab
Method: X-RAY DIFFRACTION / Resolution: 1.78 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • influenza a virus
KeywordsVIRAL PROTEIN / influenza / hemagglutinin / antibody / ANTIVIRAL PROTEIN / anti-idiotype

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