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References

Abstract

Antibodies are ideal for controlling the influenza A virus, but their effect on newly emerging strains is unclear. Here, we assessed the neutralization activity of the humanized monoclonal antibodies (mAbs) F10, H98 and H40 against circulating influenza viruses (H5N1, H1N1, H3N2 and H7N7 and new subtypes viruses H5N6 and H7N9). The results showed that all the three humanized mAbs (F10, H98 and H40) displayed different degrees of virus neutralization activities when encountered with different subtypes of influenza viruses. Remarkably, the humanized monoclonal antibody F10 produced higher and broader neutralization titers (range 25–۱٫۵۶ μg/ml) than those of the other two humanized mAbs (H98 (range 50–۳٫۱۲ μg/ml), H40 (range 50–۵٫۵۶ μg/ml)) to against the viruses H5N1, H1N1, H3N2, H7N7, H5N6 and H7N9. This mAb may represent a new class of heterosubtypic neutralizing humanized mAb that could replace vaccines and chemical drugs.

In recent years, incidences of viruses H7N9, H5N1 and epidemic of viruses H3N2, H1N1 have increased, leading to dramatic impacts on human health. Currently, the main measures to combat with influenza viruses are vaccines and antiviral treatments. Vaccines can’t provide a protective effect against the current new subtypes of influenza strains [1]. Antiviral drugs only exert therapeutic effects before drug-resistant strains emerge; but their effect when used as a late treatment is not clear [2,3]. As an effective complement to vaccines and chemical anti-viral drugs, high-affinity antibodies against conserved epitopes of viral proteins not only can provide immunotherapy to multiple influenza subtypes and but also can prevent future pandemic viruses [4,5]. The high titers of antibodies isolated from influenza-infected patients can be effectively used to treat patients with severe clinical symptoms resulting from influenza viruses; however, they provide limited rehabilitation, and it is not easy to obtain large amounts of plasma [6]. Furthermore, serum antibody titers are not uniform across different people. Therefore, to further industrializing the production of humanized antibodies is an inevitable trend.

Here, we performed experiments to analyze the microneutralization activity of the influenza A virus humanized mAbs F10, H98 and H40. These mAbs have been successfully prepared and preliminarily identified by our laboratory. Our investigation revealed that the humanized mAbs F10, H98 and H40 identified by our laboratory have active antiviral effects on four newly discovered (H1, H3, H5 and H7 viruses), four previously identified (H5N1, H1N1, H3N2 and H7N7) and two newly emerging (H5N6 and H7N9) strains.