Abstract
Andes orthohantavirus (ANDV) is the etiologic agent of hantavirus cardiopulmonary syndrome (HCPS), which has a case fatality rate around 35%, with no effective treatment or vaccine available. ANDV neutralizing antibody (NAb) measurements are important for the evaluation of the immune response following infection, vaccination, or passive administration of investigational monoclonal or polyclonal antibodies. The standard assay for NAb measurement is a focus reduction neutralization test (FRNT) featuring live ANDV and must be completed under biosafety level (BSL)-3 conditions. In this study, we compared neutralization assays featuring infectious ANDV or vesicular stomatitis virus (VSV) pseudovirions decorated with ANDV glycoproteins for their ability to measure anti-ANDV NAbs from patient samples. Our studies demonstrate that VSV pseudovirions effectively measure NAb from clinical samples and have greater sensitivity compared to FRNT with live ANDV. Importantly, the pseudovirus assay requires less labor and sample materials and can be conducted at BSL-2.
Highlights
Cecilia Vial 1*, Annalis Whitaker 2,3, Jan Wilhelm 1,4, Jimena Ovalle 1, Ruth Perez 1, Francisca Valdivieso 4, Marcela Ferres 5, Constanza Martinez-Valdebenito 5, Philip Eisenhauer 2, Gregory J
In gray is the confidence interval (95%). (B) Spearman correlation of neutralizing antibody (NAb) titer measured at UVM via replication-competent rVSV/ANDVGP plaque reduction neutralization tests (PRNTs) vs. orthohantavirus focus reduction neutralization test (FRNT)
Del Desarrollo in Chile, while the replication-competent rVSV/ANDVGP PRNT and infectious Andes orthohantavirus (ANDV) FRNT were conducted at the University of Vermont in the USA
Summary
Cecilia Vial 1*, Annalis Whitaker 2,3 , Jan Wilhelm 1,4 , Jimena Ovalle 1 , Ruth Perez 1 , Francisca Valdivieso 4 , Marcela Ferres 5 , Constanza Martinez-Valdebenito 5 , Philip Eisenhauer 2 , Gregory J. Andes orthohantavirus (ANDV) is the etiologic agent of hantavirus cardiopulmonary syndrome (HCPS), which has a case fatality rate around 35%, with no effective treatment or vaccine available. We compared neutralization assays featuring infectious ANDV or vesicular stomatitis virus (VSV) pseudovirions decorated with ANDV glycoproteins for their ability to measure anti-ANDV NAbs from patient samples. Our studies demonstrate that VSV pseudovirions effectively measure NAb from clinical samples and have greater sensitivity compared to FRNT with live ANDV. We included samples from 40 negative household contacts of HCPS cases that were obtained between 1 and 5 weeks after HCPS index case detection These contacts were followed for 40 days, remaining serologically negative to ANDV and no symptom development. Andes orthohantavirus (ANDV), the etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in Chile and Argentina, has a case fatality rate of 35%
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