Attenuation of live respiratory syncytial virus vaccines is associated with reductions in levels of nasal cytokines

Ruth A Karron, Bhagvanji Thumar, Elizabeth Schappell, Ursula J. Buchholz, Peter L. Collins

Research output: Contribution to journalArticle

Abstract

Background. Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract illness (LRTI) in children. Several promising live-attenuated RSV vaccines are in development. Defining additional markers of attenuation could enhance clinical trials.Methods. We used clinical data, virologic data, and nasal wash (NW) specimens from 20 RSV-naive children enrolled in studies of 4 live-attenuated RSV vaccines. Seven received minimally attenuated cpts248/955 or cpts530/1009 (group 1), 6 received moderately attenuated cpts248/404 (group 2), and 7 received highly attenuated rA2cp248/404/1030/ΔSH (group 3). NW specimens were tested for cytokines and chemokines via an electrochemiluminescence biosensor assay.Results. Group 1 exhibited 1 instance of LRTI and significantly higher rates of fever than groups 2 or 3; there were no significant differences in peak titers of vaccine virus in NW specimens. In contrast, levels of interferon γ;, interleukin 1β, interleukin 2, interleukin 6, and interleukin 13 were significantly greater in NW specimens from group 1, compared with those from group 3. Maximum increases in levels of most cytokines occurred after peak viral replication but coincided with clinical illness.Conclusions. Substantial increases in proinflammatory, antiinflammatory, T-helper 1, T-helper 2, and regulatory cytokines were detected in children who received minimally attenuated live RSV vaccines but not in children who received highly attenuated vaccines. Levels of cytokines in NW specimens may be useful biomarkers of attenuation for live RSV vaccines.

Original languageEnglish (US)
Pages (from-to)1773-1779
Number of pages7
JournalJournal of Infectious Diseases
Volume207
Issue number11
DOIs
StatePublished - Jun 1 2013

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Respiratory Syncytial Virus Vaccines
Nose
Attenuated Vaccines
Cytokines
Respiratory Syncytial Viruses
Respiratory System
Interleukin-13
Biosensing Techniques
Viral Load
Interleukin-1
Chemokines
Interferons
Interleukin-2
Interleukin-6
Anti-Inflammatory Agents
Fever
Vaccines
Biomarkers
Clinical Trials

Keywords

  • cytokine
  • live-attenuated vaccine
  • respiratory syncytial virus

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Attenuation of live respiratory syncytial virus vaccines is associated with reductions in levels of nasal cytokines. / Karron, Ruth A; Thumar, Bhagvanji; Schappell, Elizabeth; Buchholz, Ursula J.; Collins, Peter L.

In: Journal of Infectious Diseases, Vol. 207, No. 11, 01.06.2013, p. 1773-1779.

Research output: Contribution to journalArticle

Karron, Ruth A ; Thumar, Bhagvanji ; Schappell, Elizabeth ; Buchholz, Ursula J. ; Collins, Peter L. / Attenuation of live respiratory syncytial virus vaccines is associated with reductions in levels of nasal cytokines. In: Journal of Infectious Diseases. 2013 ; Vol. 207, No. 11. pp. 1773-1779.
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