A randomized study of fever prophylaxis and the immunogenicity of routine pediatric vaccinations

• Published in: Vaccine Vol. 35; no. 15; pp. 1926 - 1935
• Main Authors: Wysocki, Jacek, Center, Kimberly J., Brzostek, Jerzy, Majda-Stanislawska, Ewa, Szymanski, Henryk, Szenborn, Leszek, Czajka, Hanna, Hasiec, Barbara, Dziduch, Jerzy, Jackowska, Teresa, Witor, Anita, Kopińska, Elżbieta, Konior, Ryszard, Giardina, Peter C., Sundaraiyer, Vani, Patterson, Scott, Gruber, William C., Scott, Daniel A., Gurtman, Alejandra
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 04.04.2017; Elsevier Limited
• Subjects: acetaminophen; Acetaminophen - administration & dosage; Allergy and Immunology; Analgesics; antibodies; Antibodies, Bacterial - blood; Antigens; Antipyretic; antipyretics; Antipyretics - administration & dosage; Chemoprevention - methods; Combined vaccines; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine - adverse effects; disease control; Drug Interactions; Female; Fever; Fever - prevention & control; Haemophilus Vaccines - adverse effects; Hemagglutinins; Hepatitis; Hepatitis B Vaccines - adverse effects; Hepatitis B virus; Humans; Ibuprofen; Ibuprofen - administration & dosage; Immune response; Immunogenicity; Immunoglobulin G; Infant; Infants; Male; Nonsteroidal anti-inflammatory drugs; Opsonin Proteins - blood; Paracetamol; Pediatrics; Pertussis; Phagocytosis; Pneumococcal conjugate vaccine; Pneumococcal Vaccines - administration & dosage; Pneumococcal Vaccines - adverse effects; Pneumococcal Vaccines - immunology; Poliovirus Vaccine, Inactivated - adverse effects; Prophylaxis; Serotypes; Streptococcus infections; Streptococcus pneumoniae; Tetanus; vaccination; Vaccines; Vaccines, Combined - adverse effects; Whooping cough; LLOQ; OPA; Pneumococcal conjugate vaccine; PCV; PCV13; Immune response; AE; IgG; Infant; GMR; mITT; GMT; Paracetamol; SAE; DTaP/HBV/IPV/Hib; Ibuprofen; Antipyretic; GMC; FHA; geometric mean concentration; diphtheria-tetanus-acellular pertussis, hepatitis B, inactivated poliovirus, and H influenzae type b (INFANRIX ® hexa); geometric mean titer; serious adverse event; pneumococcal conjugate vaccine; immunoglobulin G; lower limit of quantitation; opsonophagocytic activity; adverse event; geometric mean ratio; 13-valent pneumococcal conjugate vaccine; modified intent to treat; filamentous hemagglutinin
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2017.02.035

Prophylactic antipyretic use during pediatric vaccination is common. This study assessed whether paracetamol or ibuprofen prophylaxis interfere with immune responses to the 13-valent pneumococcal conjugate vaccine (PCV13) given concomitantly with the combined DTaP/HBV/IPV/Hib vaccine. Subjects received prophylactic paracetamol or ibuprofen at 0, 6–8, and 12–16 h after vaccination, or 6–8 and 12–16 h after vaccination at 2, 3, 4, and 12months of age. At 5 and 13months, immune responses were evaluated versus responses in controls who received no prophylaxis. After the infant series, paracetamol recipients had lower levels of circulating serotype-specific pneumococcal anticapsular immunoglobulin G than controls, reaching significance (P<0.0125) for 5 serotypes (serotypes 3, 4, 5, 6B, and 23F) when paracetamol was started at vaccination. Opsonophagocytic activity assay (OPA) results were similar between groups. Ibuprofen did not affect pneumococcal responses, but significantly (P<0.0125) reduced antibody responses to pertussis filamentous hemagglutinin and tetanus antigens after the infant series when started at vaccination. No differences were observed for any group after the toddler dose. Prophylactic antipyretics affect immune responses to vaccines; these effects vary depending on the vaccine, antipyretic agent, and time of administration. In infants, paracetamol may interfere with immune responses to pneumococcal antigens, and ibuprofen may reduce responses to pertussis and tetanus antigens. The use of antipyretics for fever prophylaxis during infant vaccination merits careful consideration. ClinicalTrials.gov identifier: NCT01392378https://clinicaltrials.gov/ct2/show/NCT01392378?term=NCT01392378&rank=1