TY - JOUR
T1 - Attenuation of live respiratory syncytial virus vaccines is associated with reductions in levels of nasal cytokines
AU - Karron, Ruth A.
AU - Thumar, Bhagvanji
AU - Schappell, Elizabeth
AU - Buchholz, Ursula J.
AU - Collins, Peter L.
N1 - Funding Information:
Financial support. This work was supported by the National Institutes of Health (NIH; contracts N01-AI-15444 and HHSN272200900010C). U. J. B. and P. L. C. were supported by the Intramural Research Program, National Institute of Allergy and Infectious Diseases, NIH. Potential conflicts of interest. All authors: No reported conflicts.
PY - 2013/6/1
Y1 - 2013/6/1
N2 - 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.
AB - 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.
KW - cytokine
KW - live-attenuated vaccine
KW - respiratory syncytial virus
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U2 - 10.1093/infdis/jit089
DO - 10.1093/infdis/jit089
M3 - Article
C2 - 23482643
AN - SCOPUS:84877261585
SN - 0022-1899
VL - 207
SP - 1773
EP - 1779
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -