Development of a Kinetic ELISA and Reactive B Cell Frequency Assay to Detect Respiratory Syncytial Virus Pre-Fusion F Protein-Specific Immune Responses in Infants

Author:

Rolsma Stephanie L1ORCID,Yoder Sandra M1,Nargi Rachel S2,Brady Eric1,Kose Nurgun2,Jimenez-Truque Natalia1ORCID,Thomsen Isaac1,Kontos Marissa3,Carnahan Robert H2,Sutton Rachel E2,Armstrong Erica2,Dally Len3,Crowe James E2,Edwards Kathryn M1ORCID,Creech C Buddy1

Affiliation:

1. Vanderbilt Vaccine Research Program and Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center , Nashville, Tennessee , USA

2. Vanderbilt Vaccine Center, Department of Pediatrics, and Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center , Nashville, Tennessee , USA

3. The Emmes Company , LLC, Rockville, Maryland , USA

Abstract

Abstract Background Respiratory syncytial virus (RSV) is a major cause of respiratory disease in infants, making vaccination an attractive preventive strategy. Due to earlier reports of vaccine-enhanced disease in RSV-naive children, assessing prior RSV infection is critical for determining eligibility for future infant vaccine trials. However, this is complicated by the presence of maternally transferred maternal antibodies. We sought to develop assays that measure immune responses to RSV pre-fusion (F) protein that discriminates between maternal and infant responses. Methods We measured RSV-specific responses in two groups of children <3 years of age; those with laboratory-confirmed RSV (RSV-infected) and those enrolled prior to their first RSV season (RSV-uninfected). Serial blood samples were obtained and recent infections with RSV and other respiratory viruses were assessed during follow-up. An RSV pre-F-specific kinetic enzyme-linked immunosorbent assay (kELISA) and an F-specific reactive B cell frequency (RBF) assay were developed. Results One hundred two young children were enrolled between July 2015 and April 2017; 74 were in the RSV-uninfected group and 28 were in the RSV-infected group. Participants were asked to provide sequential blood samples over time, but only 53 participants in the RSV-uninfected group and 22 participants in the RSV-infected groups provided multiple samples. In the RSV-infected group, most had positive kELISA and RBF during the study. In the RSV-uninfected group, two patterns emerged: declining kELISA values without reactive B cells, due to maternal transplacental antibody transfer, and persistently positive kELISA with reactive B cells, due to asymptomatic undiagnosed RSV infection. Conclusions A kELISA targeting RSV pre-F epitopes and an RBF assay targeting RSV F-specific B cells generally allow discrimination between maternally and infant-derived antibodies.

Funder

U.S. Department of Health and Human Services

National Institutes of Health

National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,General Medicine,Pediatrics, Perinatology and Child Health

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