Topical application of human-derived Ig isotypes for the control of acute respiratory infection evaluated in a human CD89-expressing mouse model

We developed a novel CD89 Tg mouse and utilised it to compare the effectiveness of topically applied human polyclonal monomeric IgA (mIgA), polymeric IgA containing IgM (IgAM) and IgAM associated with the secretory component (SIgAM) to IgG preparations for the treatment of currently circulating and antigenically distinct influenza virus infection.A CD89 Tg mouse line on the C57BL/6 background was generated using a construct containing the full-length human CD89 cDNA followed by an internal ribosomal entry site (IRES) and green fluorescent protein (GFP) cDNA, all downstream of a loxP-flanked mCherry cassette under the control of the CMV promotor. The CD89tg/wt mice were crossed with C57BL/6 LyzMcre/cre Tg mice to excise the loxP-flanked mCherry cassette in vivo and drive CD89 expression within the myeloid cell lineage under the CMV promoter in 50% of the offspring.In our studies, both IgG and IgA protected mice from a lethal dose of PR8 virus and for mIgA, this effect was partially CD89-dependent. Our data support the beneficial effect of topically applied Ig purified from pooled human plasma for controlling circulating and non-circulating influenza virus infections. This may be important for reducing morbidity in primary immunodeficiency (PID) patients.