Antibodies directed towards neuraminidase control disease in a mouse Model of influenza

JOB EMMA; IBAÑEZ LORENA ITATÍ; SCHOTSAERT, MICHAEL; SMET ANOUK; YSENBAERT TINE; HYUSMAN ILSE; SAELENS XAVIER

Siena

Congreso; NSV meeting; 2015

Influenza A virus (IAV) carries two major surface glycoproteins; the hemagglutinin (HA) and the neuraminidase (NA), both important for successful virus entry and release from cells. The immune response towards NA, in comparison to HA, is far less studied. We aimed to isolate monoclonal antibodies (mAb) with antiviral activity against the N1 subtype of IAV to gain a greater understanding of the Ab response to IAV NA. Mouse hybridomas were generated expressing mAb directed towards N1 NAs. One set of mAbs, including 7D3, could all bind to recombinant NA derived from H1 N1 viruses; A/USSR/1 977, A/Singapore/1 986, A/New Caledonia/1 999, A/Brisbane/2007 and A/Belgium/2009 (Bel/09), but were unable to inhibit NA activity. In contrast, mAb CD4 was able to (i) bind NA, (ii) inhibit the NA activity, and (iii) reduce plaque size formation of both Bel/09 and NIBRG-1 4 (a 6:2 reverse genetic H5N1 virus expressing the HA and NA of A/Vietnam/1 1 94/2004). mAb 7D3 and CD4 were selected for testing their ability to protect against disease in a mouse model of influenza virus infection. Administration of mAb 7D3 did not alter morbidity and mortality of mice infected with lethal doses of any N1 IAV tested. Mice treated with mAb CD4 however, were protected from a lethal infection with Bel/09 and NIBRG-1 4. Interestingly, mAb CD4 significantly reduced lung-viral loads in mice infected with Bel/09 but not NIBRG-1 4. These results suggest that anti-NA Abs that have NA inhibitory activity can control IAV infection.