RESUMO
BACKGROUND: The key correlate of protection of respiratory syncytial virus (RSV) vaccines and monoclonal antibodies (mAbs) is virus neutralization, measured via sera obtained through venipuncture. Dried blood obtained with a finger prick can simplify acquisition, processing, storage, and transport in trials and thereby reduce costs. In this study, we validate an assay to measure RSV neutralization in dried capillary blood. METHODS: Functional antibodies were compared between matched serum and dried blood samples from a phase 1 trial with RSM01, an investigational anti-RSV prefusion F mAb. Hep-2 cells were infected with a serial dilution of sample-virus mixture by using RSV-A2-mKate to determine the half-maximal inhibitory concentration. Stability of dried blood was evaluated over time and during temperature stress. RESULTS: Functional antibodies in dried blood were highly correlated with serum (R2 = 0.98, P < .0001). The precision of the assay for dried blood was similar to serum. The function of mAb remained stable for 9 months at room temperature and frozen dried blood samples. CONCLUSIONS: We demonstrated the feasibility of measuring RSV neutralization using dried blood as a patient-centered solution that may replace serology testing in trials against RSV or other viruses, such as influenza and SARS-CoV-2. Clinical Trials Registration. NCT05118386 (ClinicalTrials.gov).
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Teste em Amostras de Sangue Seco/métodos , Testes de Neutralização/métodos , Anticorpos Monoclonais/imunologiaRESUMO
BACKGROUND: The key correlate of protection of respiratory syncytial virus (RSV) vaccines and monoclonal antibodies (mAb) is virus neutralization, measured using sera obtained through venipuncture. Dried blood obtained with a finger prick can simplify acquisition, processing, storage, and transport in trials, and thereby reduce costs. In this study we validate an assay to measure RSV neutralization in dried capillary blood. METHODS: Functional antibodies were compared between matched serum and dried blood samples from a phase I trial with RSM01, an investigational anti-RSV Prefusion F mAb. Hep-2 cells were infected with a serial dilution of sample-virus mixture using RSV-A2-mKate to determine half-maximal inhibitory concentration. Stability of dried blood was evaluated over time and during temperature stress. RESULTS: Functional antibodies in dried blood were highly correlated with serum (R2 = 0.98, p < 0.0001). The precision of the assay for dried blood was similar to serum. The function of mAb remained stable for 9 months at room temperature and frozen dried blood samples. INTERPRETATION: We demonstrated the feasibility of measuring RSV neutralization using dried blood as a patient-centered solution that may replace serology testing in trials against RSV or other viruses, such as influenza and SARS-CoV-2.