tetano
Editor, Senior Moderator
NPJ Vaccines. 2017 Jul 6;2:18. doi: 10.1038/s41541-017-0020-x. eCollection 2017.
[h=1]DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections.[/h] Elliott STC[SUP]#[/SUP][SUP]1[/SUP], Kallewaard NL[SUP]2[/SUP], Benjamin E[SUP]2[/SUP], Wachter-Rosati L[SUP]2[/SUP], McAuliffe JM[SUP]2[/SUP], Patel A[SUP]1[/SUP], Smith TRF[SUP]3[/SUP], Schultheis K[SUP]3[/SUP], Park DH[SUP]1[/SUP], Flingai S[SUP]1[/SUP], Wise MC[SUP]1[/SUP], Mendoza J[SUP]3[/SUP], Ramos S[SUP]3[/SUP], Broderick KE[SUP]3[/SUP], Yan J[SUP]3[/SUP], Humeau LM[SUP]3[/SUP], Sardesai NY[SUP]3[/SUP], Muthumani K[SUP]1[/SUP], Zhu Q[SUP]2[/SUP], Weiner DB[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus remains a significant public health threat despite innovative vaccines and antiviral drugs. A major limitation to current vaccinations and therapies against influenza virus is pathogenic diversity generated by shift and drift. A simple, cost-effective passive immunization strategy via in vivo production of cross-protective antibody molecules may augment existing vaccines and antiviral drugs in seasonal and pandemic outbreaks. We engineered synthetic plasmid DNA to encode two novel and broadly cross-protective monoclonal antibodies targeting influenza A and B. We utilized enhanced in vivo delivery of these plasmid DNA-encoded monoclonal antibody (DMAb) constructs and show that this strategy induces robust levels of functional antibodies directed against influenza A and B viruses in mouse sera. Mice receiving a single inoculation with anti-influenza A DMAb survive lethal Group 1 H1 and Group 2 H3 influenza A challenges, while inoculation with anti-influenza B DMAb yields protection against lethal Victoria and Yamagata lineage influenza B morbidity and mortality. Furthermore, these two DMAbs can be delivered coordinately resulting in exceptionally broad protection against both influenza A and B. We demonstrate this protection is similar to that achieved by conventional protein antibody delivery. DMAbs warrant further investigation as a novel immune therapy platform with distinct advantages for sustained immunoprophylaxis against influenza.
PMID: 29263874 PMCID: PMC5627301 DOI: 10.1038/s41541-017-0020-x
[h=1]DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections.[/h] Elliott STC[SUP]#[/SUP][SUP]1[/SUP], Kallewaard NL[SUP]2[/SUP], Benjamin E[SUP]2[/SUP], Wachter-Rosati L[SUP]2[/SUP], McAuliffe JM[SUP]2[/SUP], Patel A[SUP]1[/SUP], Smith TRF[SUP]3[/SUP], Schultheis K[SUP]3[/SUP], Park DH[SUP]1[/SUP], Flingai S[SUP]1[/SUP], Wise MC[SUP]1[/SUP], Mendoza J[SUP]3[/SUP], Ramos S[SUP]3[/SUP], Broderick KE[SUP]3[/SUP], Yan J[SUP]3[/SUP], Humeau LM[SUP]3[/SUP], Sardesai NY[SUP]3[/SUP], Muthumani K[SUP]1[/SUP], Zhu Q[SUP]2[/SUP], Weiner DB[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus remains a significant public health threat despite innovative vaccines and antiviral drugs. A major limitation to current vaccinations and therapies against influenza virus is pathogenic diversity generated by shift and drift. A simple, cost-effective passive immunization strategy via in vivo production of cross-protective antibody molecules may augment existing vaccines and antiviral drugs in seasonal and pandemic outbreaks. We engineered synthetic plasmid DNA to encode two novel and broadly cross-protective monoclonal antibodies targeting influenza A and B. We utilized enhanced in vivo delivery of these plasmid DNA-encoded monoclonal antibody (DMAb) constructs and show that this strategy induces robust levels of functional antibodies directed against influenza A and B viruses in mouse sera. Mice receiving a single inoculation with anti-influenza A DMAb survive lethal Group 1 H1 and Group 2 H3 influenza A challenges, while inoculation with anti-influenza B DMAb yields protection against lethal Victoria and Yamagata lineage influenza B morbidity and mortality. Furthermore, these two DMAbs can be delivered coordinately resulting in exceptionally broad protection against both influenza A and B. We demonstrate this protection is similar to that achieved by conventional protein antibody delivery. DMAbs warrant further investigation as a novel immune therapy platform with distinct advantages for sustained immunoprophylaxis against influenza.
PMID: 29263874 PMCID: PMC5627301 DOI: 10.1038/s41541-017-0020-x