Presentation Title

An investigation into the natural history and specificity of the humoral immune response to Andes orthohantavirus infection in humans

Project Collaborators

Philip Eisenhauer (Lab Technician); Emily Bruce (Faculty Scientist); Colleen Cooper (Business Collaborator); Pablo Vial (Physician); Cecilia Vial (International Collaborator)

Abstract

Lethal outbreaks of hantavirus cardiopulmonary syndrome (HCPS) caused by Andes orthohantavirus (ANDV) are rising in frequency and geographic distribution in South America. Despite access to advanced medical care, HCPS mortality still reaches 30-50%. The development of virus-specific neutralizing antibodies (nAb) is thought to be an immune correlate of protection from severe HCPS, with a majority of nAb recognizing the viral envelope glycoprotein (GP). However, little is known regarding the kinetics of antibody formation against the ANDV proteome during acute infection and subsequent convalescence. We developed strip immunoblot and ELISA assays for detection of ANDV-specific antibodies from the serum of ANDV patients. Using these assays we have mapped the dynamics of antibody generation against the Andes virus GP, nucleoprotein (N), and nonstructural protein of the S segment (NSs) during acute disease and convalescence and observed antibodies with considerable cross-reactivity to both ANDV and the North American Sin Nombre orthohantavirus. We also measured nAbs over this the time course and hypothesized that patients with mild disease would have higher levels of nAb during acute infection compared to patients with severe disease. However, in our patient cohort, levels of nAb did not appear to correlate with disease severity. In summary, our study provides a novel map of the natural history and specificity of the humoral immune response to ANDV infection in humans.

Primary Faculty Mentor Name

Jason Botten

Status

Graduate

Student College

Larner College of Medicine

Program/Major

Cellular, Molecular and Biomedical Sciences

Primary Research Category

Biological Sciences

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An investigation into the natural history and specificity of the humoral immune response to Andes orthohantavirus infection in humans

Lethal outbreaks of hantavirus cardiopulmonary syndrome (HCPS) caused by Andes orthohantavirus (ANDV) are rising in frequency and geographic distribution in South America. Despite access to advanced medical care, HCPS mortality still reaches 30-50%. The development of virus-specific neutralizing antibodies (nAb) is thought to be an immune correlate of protection from severe HCPS, with a majority of nAb recognizing the viral envelope glycoprotein (GP). However, little is known regarding the kinetics of antibody formation against the ANDV proteome during acute infection and subsequent convalescence. We developed strip immunoblot and ELISA assays for detection of ANDV-specific antibodies from the serum of ANDV patients. Using these assays we have mapped the dynamics of antibody generation against the Andes virus GP, nucleoprotein (N), and nonstructural protein of the S segment (NSs) during acute disease and convalescence and observed antibodies with considerable cross-reactivity to both ANDV and the North American Sin Nombre orthohantavirus. We also measured nAbs over this the time course and hypothesized that patients with mild disease would have higher levels of nAb during acute infection compared to patients with severe disease. However, in our patient cohort, levels of nAb did not appear to correlate with disease severity. In summary, our study provides a novel map of the natural history and specificity of the humoral immune response to ANDV infection in humans.