Comparing NKT cell therapy to oseltamivir phosphate (Tamiflu®) for controlling pandemic H1N1 influenza

Abstract

Abstract The continuing global burden of disease from influenza infections reveals an urgent need for new approaches that more efficiently protect and potentially avoid the emergence of drug-resistant strains over time. One strategy could be to therapeutically target natural killer T (NKT) cells, an innate-like lymphocyte subset capable of inducing potent antiviral immune responses. We previously reported that disease outcome is significantly improved when influenza-infected pigs are intranasally treated with the NKT cell superagonist α-galactosylceramide (αGC). Here, we compared the protective effects of αGC to 7DW8-5, an αGC derivative that promotes pro-inflammatory immune responses, as well as oseltamivir phosphate (Tamiflu®), a neuraminidase inhibitor used to treat and prevent influenza. A total of 20 pigs challenged with H1N1 A/California/04/2009 (CA04) (4 per group) were administered vehicle, 7DW8-5, or αGC and Tamiflu®, alone or in combination. Four other pigs were mock infected and vehicle treated. Symptoms, viral shedding and peripheral blood leukocytes were measured for 7 days post infection (dpi). Pigs were then euthanized to examine viral titers and immune responses in the airway and lymphoid organs. Pigs treated with αGC and 7DW8-5 but not Tamiflu restored weight gain of infected pigs to the level of un-infected animals. All treatments eliminated virus shedding by 2 dpi compared to infected and untreated pigs that continued to shed virus throughout the study. So far, our results suggest that NKT cell therapy is similar to Tamiflu® for reducing the severity and transmission of influenza infections in pigs. Thus, it may be possible to use NKT cell superagonists to limit the spread of influenza viruses amongst swine and humans.