Evaluation of candidate reference materials for the harmonization of Lassa fever serology.

Lassa fever is a zoonotic disease endemic to several West African countries, with seasonal outbreaks and potential to cause future epidemics. Vaccines and other medical countermeasures are in development, requiring reliable assays for evaluation. A WHO International Standard (IS) for anti-Lassa virus (LASV) antibodies can support harmonization of serological assay results, aiding vaccine and therapeutic assessment, surrogates of protection identification, and improving epidemiological understanding. In this study, a pooled plasma sample from Lassa fever survivors was evaluated in a multi-centre collaborative study involving 17 laboratories for its suitability as a reference material for detecting anti-LASV antibodies. Additionally, two well-characterized monoclonal antibody (mAb) cocktails were assessed as potential alternatives to convalescent plasma. Expressing the antibody titre of the collaborative study panel samples relative to the convalescent plasma pool (NIBSC 20/202) or the mAb cocktails harmonized the results from the participants reducing the inter-laboratory variation. However, while the candidate IS 20/202 performed consistently across all assays, the mAb cocktails were not detected by a few binding antibody methods. These findings support the use of mAb cocktails as reference material for evaluating humoral responses within a laboratory or network using common assays; however, for an IS, applicable globally across methods, convalescent serum or plasma remains the most suitable material.