ABSTRACT
Live attenuated influenza vaccine (LAIV) is considered one of the most effective vaccines and can be manufactured quickly and inexpensively to counter seasonal or pandemic influenza. Lyophilization is widely used in vaccine production. However, it requires a longer production cycle and large-scale equipment, thus posing a considerable financial burden for developing countries. A potential solution is the development of liquid LAIV, which can increase the yield and reduce the cost of production. In this study, influential factors of LAIV, such as potential stabilizing excipients and pH, were optimized by an orthogonal design. We found that pH is the most critical factor for the stability of LAIV; salt concentration and initial virus titer are also important for LAIV stability. With these data, we developed a liquid formulation consisting of 2.5% sucrose, 0.1% monosodium glutamate, 1% arginine, and 0.5% human serum albumin, with pH ranging from 6.2 to 6.9 (optimum pH 6.5-6.7), for optimal production of monovalent or trivalent LAIVs. This liquid formulation has the potential to considerably improve vaccine production capacity to compensate for the immense shortfall in influenza vaccines globally.
