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Sci Transl Med. 2017 Oct 18;9(412). pii: eaam5752. doi: 10.1126/scitranslmed.aam5752.
A multimechanistic antibody targeting the receptor binding site potently cross-protects against influenza B viruses.
Shen C1, Chen J1, Li R1, Zhang M1, Wang G1, Stegalkina S2, Zhang L1, Chen J1, Cao J1, Bi X1, Anderson SF2, Alefantis T2, Zhang M3, Cai X3, Yang K4, Zheng Q1, Fang M1, Yu H1, Luo W1, Zheng Z1, Yuan Q1, Zhang J1, Wai-Kuo Shih J1, Kleanthous H2, Chen H1,5, Chen Y6, Xia N6.
Author information
Abstract
Influenza B virus causes considerable disease burden worldwide annually, highlighting the limitations of current influenza vaccines and antiviral drugs. In recent years, broadly neutralizing antibodies (bnAbs) against hemagglutinin (HA) have emerged as a new approach for combating influenza. We describe the generation and characterization of a chimeric monoclonal antibody, C12G6, that cross-neutralizes representative viruses spanning the 76 years of influenza B antigenic evolution since 1940, including viruses belonging to the Yamagata, Victoria, and earlier lineages. Notably, C12G6 exhibits broad cross-lineage hemagglutination inhibition activity against influenza B viruses and has higher potency and breadth of neutralization when compared to four previously reported influenza B bnAbs. In vivo, C12G6 confers stronger cross-protection against Yamagata and Victoria lineages of influenza B viruses in mice and ferrets than other bnAbs or the anti-influenza drug oseltamivir and has an additive antiviral effect when administered in combination with oseltamivir. Epitope mapping indicated that C12G6 targets a conserved epitope that overlaps with the receptor binding site in the HA region of influenza B virus, indicating why it neutralizes virus so potently. Mechanistic analyses revealed that C12G6 inhibits influenza B viruses via multiple mechanisms, including preventing viral entry, egress, and HA-mediated membrane fusion and triggering antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity responses. C12G6 is therefore a promising candidate for the development of prophylactics or therapeutics against influenza B infection and may inform the design of a truly universal influenza vaccine.
Copyright ? 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
PMID: 29046433 DOI: 10.1126/scitranslmed.aam5752
A multimechanistic antibody targeting the receptor binding site potently cross-protects against influenza B viruses.
Shen C1, Chen J1, Li R1, Zhang M1, Wang G1, Stegalkina S2, Zhang L1, Chen J1, Cao J1, Bi X1, Anderson SF2, Alefantis T2, Zhang M3, Cai X3, Yang K4, Zheng Q1, Fang M1, Yu H1, Luo W1, Zheng Z1, Yuan Q1, Zhang J1, Wai-Kuo Shih J1, Kleanthous H2, Chen H1,5, Chen Y6, Xia N6.
Author information
Abstract
Influenza B virus causes considerable disease burden worldwide annually, highlighting the limitations of current influenza vaccines and antiviral drugs. In recent years, broadly neutralizing antibodies (bnAbs) against hemagglutinin (HA) have emerged as a new approach for combating influenza. We describe the generation and characterization of a chimeric monoclonal antibody, C12G6, that cross-neutralizes representative viruses spanning the 76 years of influenza B antigenic evolution since 1940, including viruses belonging to the Yamagata, Victoria, and earlier lineages. Notably, C12G6 exhibits broad cross-lineage hemagglutination inhibition activity against influenza B viruses and has higher potency and breadth of neutralization when compared to four previously reported influenza B bnAbs. In vivo, C12G6 confers stronger cross-protection against Yamagata and Victoria lineages of influenza B viruses in mice and ferrets than other bnAbs or the anti-influenza drug oseltamivir and has an additive antiviral effect when administered in combination with oseltamivir. Epitope mapping indicated that C12G6 targets a conserved epitope that overlaps with the receptor binding site in the HA region of influenza B virus, indicating why it neutralizes virus so potently. Mechanistic analyses revealed that C12G6 inhibits influenza B viruses via multiple mechanisms, including preventing viral entry, egress, and HA-mediated membrane fusion and triggering antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity responses. C12G6 is therefore a promising candidate for the development of prophylactics or therapeutics against influenza B infection and may inform the design of a truly universal influenza vaccine.
Copyright ? 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
PMID: 29046433 DOI: 10.1126/scitranslmed.aam5752