Design of the Recombinant Influenza Neuraminidase Antigen Is Crucial for Its Biochemical Properties and Protective Efficacy
Jin Gao, Laura Klenow, Lisa M. Parsons, Tahir Malik, Je‐Nie Phue, Zhizeng Gao, Stephen G. Withers, John F. Cipollo, Robert Daniels, Hongquan Wan
Abstract
For several decades, it has been proposed that influenza vaccines could be supplemented with recombinant neuraminidase (rNA) to improve efficacy. However, some key questions for manufacturing stable and immunogenic rNAs remain to be answered. We show here that the tetramerization motifs and NA domains included in the rNA construct design can have a profound impact on the biochemical, immunogenic, and protective properties. We also show that the single-dose immunization regimen is more informative for assessing the rNA immune response and protective efficacy, which is surprisingly more dependent on the specific combination of NA and tetramerization domains than common attributes for evaluating NA. Our findings may help to optimize the design of rNAs that can be used to improve or develop influenza vaccines.