Qualification of a quantitative stability indicating potency assay for mRNA-LNP vaccine candidates.

Abstract

Potency assays assess the functional integrity of a target antigen to ensure that the final drug product is consistent between the commercial and clinical trial lots. Existing mRNA-LNP vaccine potency assays require complex quantification methods, such as flow cytometry, which are not widely adaptable to routine use by low- and middle-income country (LMIC) manufacturers or National Regulatory Agency (NRA) laboratories. To address the need for more accessible mRNA-LNP vaccine potency methods, an enzyme-linked immunosorbent assay (ELISA) was developed to quantify the target proteins produced by an mRNA-LNP vaccine after cell transfection. SARS-CoV-2 mRNA-LNP targeting the wild-type (Wuhan) strain was used as a model vaccine for the development and qualification of an ELISA method. The adaptability of the ELISA to other mRNA-LNP vaccines was demonstrated by altering the method used for quantification of a commercial Omicron mRNA-LNP vaccine. Alternative mRNA-LNP potency methods, such as western blotting, fluorescence focus assay (FFA), and direct ELISA were used as analogous methods for comparison. The developed quantitative stability-indicating ELISA is a globally accessible potency method that utilizes existing equipment and knowledge. Testing conducted on wild type SARS CoV-2 and Omicron vaccines demonstrates the adaptability of the method to other mRNA vaccine targets.