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Vaccines based on pathogen components require adjuvants to enhance the antigen‐specific adaptive immune response. Intramuscular injection of adjuvanted‐vaccines induces inflammatory cytokines and inflammatory nodules at the injection sites within 48 hours after injection (Vaccine 2014; 32: 3393‐3401). In the present study, the long‐term regulation of cytokine production was investigated at 3, 6, 24, and 48 h, 5 and 7 days, and 2 and 4 weeks after immunization with human papilloma virus (HPV), diphtheria and tetanus toxoids combined with acellular pertussis (DTaP), haemophilus influenzae type B (Hib), and conjugated pneumococcal (PCV) vaccines in mouse models. The second dose was administered 4 weeks later, and cytokine profiles were investigated 2, 5, and 7 days after re‐immunization. IL‐1β, IL‐6, G‐CSF, and MCP‐1 were produced from 3 h and peaked at 48 h after immunization with Cervarix in mice. IL‐4, MCP‐1, and TNF‐β peaked at 5 or 7 days after immunization with Gardasil. These cytokines decreased 7 days after immunization with Cervarix and Gardasil. After the second dose, similar responses were observed. Both vaccines induced neutrophil extracellular traps (NETs) in inflammatory nodules. The peak amount of IL‐1β, IL‐6, G‐CSF, and MCP‐1 was observed on day 5 of immunization and that of IL‐4 on day 5‐7 of immunization with DTaP, but no increase in IL‐6 and G‐CSF was observed after re‐immunization. A similar response was noted after immunization with PCV13. An inflammatory response is essential for the development of adaptive immunity through the production of inflammatory cytokines.
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