Kinetics of serum cytokines after primary or repeat vaccination with the smallpox vaccine.
BACKGROUND
The smallpox vaccine is associated with more serious adverse events than any other live attenuated vaccine in use today. Although studies have examined serum cytokine levels in primary vaccine recipients at 1 and 3-5 weeks after vaccination with the smallpox vaccine, serial measurements have not been performed, and studies in revaccinated subjects have not been conducted.


METHODS
We analyzed cytokine responses in both primary vaccine recipients and revaccinated subjects every other day for 2 weeks after vaccination.


RESULTS
Primary vaccine recipients had maximal levels of granulocyte-colony-stimulating factor on days 6-7 after vaccination; peak levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptor 1, interferon (IFN)-gamma, IFN-inducible protein-10 (IP-10), interleukin (IL)-6, and tissue inhibitor of metalloproteinases-1 on days 8-9 after vaccination; peak levels of soluble TNF receptor 2 and monokine induced by IFN-gamma (MIG) on days 10-11 after vaccination; and peak levels of granulocyte-macrophage-colony-stimulating factor on days 12-13 after vaccination. Primary vaccine recipients were significantly more likely to have higher peak levels of IFN-gamma, IP-10, and MIG after vaccination than were revaccinated subjects. Primary vaccine recipients were significantly more likely to have fatigue, lymphadenopathy, and headache, as well as a longer duration of these symptoms and more hours missed from work, compared with revaccinated subjects.


CONCLUSIONS
The increased frequency and duration of symptoms observed in primary vaccine recipients, compared with revaccinated subjects, paralleled the increases in serum cytokine levels in these individuals.


BACKGROUND
Clinicaltrials.gov identifier NCT00325975.
Cohen
Jeffrey I
JI
Medical Virology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jcohen@niaid.nih.gov
Hohman
Patricia
P
Fulton
Rachael
R
Turk
Siu-Ping
SP
Qin
Jing
J
Thatcher
Karen
K
Hornung
Ronald L
RL
D000328:Adult; D054357:Chemokine CXCL10 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007372:Interferons / Q000097:blood; D007378:Interleukins / Q000097:blood; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D015846:Monokines / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
D054357:Chemokine CXCL10; D016207:Cytokines; D007378:Interleukins; D015846:Monokines; D018124:Receptors, Tumor Necrosis Factor; D012900:Smallpox Vaccine; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D007372:Interferons