Live attenuated influenza virus vaccines: Ns1 truncation as an approach to virus attenuation

Influenza virus causes significant morbidity and mortality worldwide. Vaccination, usually involving the inactivated type of vaccine, is the primary mechanism of influenza virus prevention. Live attenuated influenza viruses (LAIV), however, are also available for the prevention of disease. These vaccines have been shown to stimulate a robust cellular response, induce IgA and IgG antibodies, and can provide heterosubtypic protection. Cold-adaptation and temperature sensitivity are two mechanisms of influenza virus attenuation, yielding viruses that are both safe and immunogenic. At present, novel attenuation strategies, including the manipulation of viral gene sequences and proteins, are being developed in the hopes of providing new LAIV vaccines. One promising strategy involves the truncation of the NS1 protein of influenza virus, limiting the interferon antagonist capabilities of the influenza pathogen. Experimental vaccines that exploit this mode of attenuation have been tested in several animal models; as summarized herein, high efficacy in reducing mortality, morbidity, and transmission of influenza viruses has been observed.