tetano
Editor, Senior Moderator
Sci Transl Med. 2017 Oct 18;9(412). pii: eaam5752. doi: 10.1126/scitranslmed.aam5752.
[h=1]A multimechanistic antibody targeting the receptor binding site potently cross-protects against influenza B viruses.[/h] Shen C[SUP]1[/SUP], Chen J[SUP]1[/SUP], Li R[SUP]1[/SUP], Zhang M[SUP]1[/SUP], Wang G[SUP]1[/SUP], Stegalkina S[SUP]2[/SUP], Zhang L[SUP]1[/SUP], Chen J[SUP]1[/SUP], Cao J[SUP]1[/SUP], Bi X[SUP]1[/SUP], Anderson SF[SUP]2[/SUP], Alefantis T[SUP]2[/SUP], Zhang M[SUP]3[/SUP], Cai X[SUP]3[/SUP], Yang K[SUP]4[/SUP], Zheng Q[SUP]1[/SUP], Fang M[SUP]1[/SUP], Yu H[SUP]1[/SUP], Luo W[SUP]1[/SUP], Zheng Z[SUP]1[/SUP], Yuan Q[SUP]1[/SUP], Zhang J[SUP]1[/SUP], Wai-Kuo Shih J[SUP]1[/SUP], Kleanthous H[SUP]2[/SUP], Chen H[SUP]1,[/SUP][SUP]5[/SUP], Chen Y[SUP]6[/SUP], Xia N[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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
[h=1]A multimechanistic antibody targeting the receptor binding site potently cross-protects against influenza B viruses.[/h] Shen C[SUP]1[/SUP], Chen J[SUP]1[/SUP], Li R[SUP]1[/SUP], Zhang M[SUP]1[/SUP], Wang G[SUP]1[/SUP], Stegalkina S[SUP]2[/SUP], Zhang L[SUP]1[/SUP], Chen J[SUP]1[/SUP], Cao J[SUP]1[/SUP], Bi X[SUP]1[/SUP], Anderson SF[SUP]2[/SUP], Alefantis T[SUP]2[/SUP], Zhang M[SUP]3[/SUP], Cai X[SUP]3[/SUP], Yang K[SUP]4[/SUP], Zheng Q[SUP]1[/SUP], Fang M[SUP]1[/SUP], Yu H[SUP]1[/SUP], Luo W[SUP]1[/SUP], Zheng Z[SUP]1[/SUP], Yuan Q[SUP]1[/SUP], Zhang J[SUP]1[/SUP], Wai-Kuo Shih J[SUP]1[/SUP], Kleanthous H[SUP]2[/SUP], Chen H[SUP]1,[/SUP][SUP]5[/SUP], Chen Y[SUP]6[/SUP], Xia N[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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