Development of a quantitative ELISA for SARS-CoV-2 vaccine candidate, NDV-HXP-S, with CpG 1018® adjuvant.

NDV-HXP-S is a Newcastle disease virus (NDV) vectored vaccine candidate which expresses the S-antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This vaccine candidate is under evaluation in human clinical studies with and without cytosine phosphate guanine (CpG) 1018® adjuvant. Existing potency methods for NDV-HXP-S do not allow for quantification of the S-antigen when the adjuvant is present. To support evaluation of NDV-HXP-S with CpG 1018® adjuvant, an inhibition enzyme-linked immunosorbent assay (ELISA) was developed to allow for quantification and stability assessments of the vaccine. A pilot 6-month stability study was conducted on NDV-HXP-S vaccine with and without CpG 1018® adjuvant under refrigerated conditions (2°C to 8°C) and accelerated stability testing conditions (40°C). The vaccine was mixed with and without CpG 1018® adjuvant in saline and maintained S-antigen content at 2°C to 8°C for the entire 6-month period. Additionally, a pilot controlled temperature chain (CTC) stability study was conducted at the completion of the 6-month study and demonstrated the possibility for this vaccine candidate to attain CTC stability labeling.

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.

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.

Identifying a stable bulk dmLT adjuvant formulation at a clinically relevant concentration.

Double mutant heat-labile toxin (dmLT) is a novel vaccine adjuvant under development with several different vaccine candidates. Studies using existing dmLT adjuvant stocks require significant dilution to achieve a clinically relevant dose. This dilution leads to wastage of the adjuvant. This manuscript describes a limited formulation study to improve the stability of bulk dmLT at a more clinically relevant concentration (20 µg/mL) with minimal changes to the existing bulk dmLT formulation. In vitro methods were used to evaluate dmLT stability after lyophilization and short-term accelerated stability studies. The addition of the excipient polysorbate 80 (PS80) at 0.05 % to the existing dmLT formulation was identified as the lead modification that provided improved stability of the lyophilized dmLT at 20 µg/mL through 4 weeks at 40 °C.