Development of multidose thermotolerant formulations of a vector-based Covid-19 vaccine candidate, NDV-HXP-S in different product formats: Stability and preservative efficacy study.

ABSTRACT

Current lead coronavirus vaccines require continuous cold or ultra-cold storage from the manufacturing site to the field to maintain protective efficacy. Since cold chain capacity is limited and complex, logistics planning is crucial to limit vaccine wastage.[1] The restrictive storage concerns also make it difficult to share vaccines between public health departments and neighboring states, leading to increased vaccine wastage.[2] A Newcastle Disease Virus (NDV) vector-based severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) vaccine candidate, NDV-HXP-S, offers a cost-effective alternative which aims to improve global access to SARS CoV-2 vaccines.[3] The NDV-HXP-S vaccine candidate can be mass-produced in chicken eggs and has demonstrated efficacy in preclinical studies, as well as acceptable safety and potent immunogenicity in clinical studies.[3,4-10] To further advance the NDV-HXP-S vaccine candidate, this manuscript describes work focused on the development of multidose thermotolerant vaccine formulations (i.e., those which would not require continuous extended refrigeration), making it convenient to use and store, and simplifying transport and distribution logistics, especially in outbreak settings. Liquid and lyophilized formulations for parenteral administration were rigorously screened for the vaccine formulation's ability to maintain S-antigen stability after exposure to temperature stress at 40 °C, 25 °C, and 2 °C to 8 °C storage for six months. Preservative efficacy was evaluated to enable a multidose liquid vaccine format as well as endotoxin testing in lyophilized formulations. Lead liquid vaccine formations were identified that were able to maintain S-antigen content at 2 °C to 8 °C and 25 °C storage for the entire six-month study. Lead lyophilized vaccine formulations were identified which were able to maintain S-antigen content for six months at 2 °C to 8 °C, 25 °C, and 40 °C. Both the liquid and lyophilized formulations identified are improved thermotolerant SARS-CoV-2 vaccine formulations.