Infants' diminished response to DTaP vaccine is associated with exposure to organophosphate esters.

Organophosphate esters (OPEs) are commonly applied as flame retardants and plasticizers. Toxicological studies suggest exposure effects on immune endpoints, raising concerns as infants' OPE exposures are elevated compared to older children and adults due to hand-to-mouth behavior and breastfeeding. Here, we sought to evaluate the immune responsiveness of infants to a neoantigen (e.g., a newly encountered antigen) in the presence of OPE exposures. As a proxy for immune responsiveness, children were given three doses of the Diphtheria, Tetanus, and Pertussis (DTaP) vaccine as recommended, and diphtheria and tetanus antibodies were evaluated in serum samples collected when children were 12 months old (n = 84). Titers were compared, based on maximum sample overlap, to measurements of OPE metabolites in spot urine samples collected before vaccination (age 2 months, n = 73) and at the time of antibody assessment (12 months of age, n = 46). Metabolites of two chlorinated OPEs were significantly associated with diminished antibodies for diphtheria and tetanus. A metabolite of tris (1,3-dichloroisopropyl)phosphate (TDCIPP) measured at 2 months was associated with decreased diphtheria antibodies (-0.07 IU/mL per log10 increase in metabolite). One metabolite of tris(2-chloroisopropyl)phosphate (TCIPP) measured at 12 months was associated with decreased tetanus antibodies (-0.57 IU/mL per log10 increase in metabolite). These results provide some preliminary insights for OPE exposure impacts on vaccine responses in early life and may have important implications for immune health through childhood and adulthood.

An observer blinded, randomized, placebo-controlled, phase I dose escalation trial to evaluate the safety and immunogenicity of an inactivated West Nile virus Vaccine, HydroVax-001, in healthy adults.

BACKGROUND: West Nile virus (WNV) is the most common mosquito-borne infection in the United States. HydroVax-001 WNV is a hydrogen peroxide inactivated, whole virion (WNV-Kunjin strain) vaccine adjuvanted with aluminum hydroxide. METHODS: We performed a phase 1, randomized, placebo-controlled, double-blind (within dosing group), dose escalation clinical trial of the HydroVax-001 WNV vaccine administered via intramuscular injection. This trial evaluated 1 mcg and 4 mcg dosages of HydroVax-001 WNV vaccine given intramuscularly on day 1 and day 29 in healthy adults. The two dosing groups of HydroVax-001 were enrolled sequentially and each group consisted of 20 individuals who received HydroVax-001 and 5 who received placebo. Safety was assessed at all study days (days 1, 2, 4 and 15 post dose 1, and days 1, 2, 4, 15, 29, 57, 180 and 365 post dose 2), and reactogenicity was assessed for 14 days after administration of each dose. Immunogenicity was measured by WNV-specific plaque reduction neutralization tests (PRNT50) in the presence or absence of added complement or by WNV-specific enzyme-linked immunosorbent assays (ELISA). RESULTS: HydroVax-001 was safe and well-tolerated as there were no serious adverse events or concerning safety signals. At the 1 mcg dose, HydroVax-001 was not immunogenic by PRNT50 but elicited up to 41% seroconversion by WNV-specific ELISA in the per-protocol population (PP) after the second dose. At the 4 mcg dose, HydroVax-001 elicited neutralizing antibody responses in 31% of the PP following the second dose. In the presence of added complement, PRNT50 seroconversion rates increased to 50%, and 75% seroconversion was observed by WNV-specific ELISA. CONCLUSIONS: The HydroVax-001 WNV vaccine was found to be modestly immunogenic and well-tolerated at all dose levels.

Open-Label Pilot Study to Compare the Safety and Immunogenicity of Pentavalent Rotavirus Vaccine (RV5) Administered on an Early Alternative Dosing Schedule with Those of RV5 Administered on the Recommended Standard Schedule.

This study compares the safety and immunogenicity of pentavalent rotavirus vaccine (RV5) administered on an alternative schedule (initiated at 2-5 weeks of age) with those of RV5 administered on the recommended standard schedule. Our findings support the future conduct of larger clinical trials to confirm the safety and efficacy of rotavirus vaccination in the neonatal period.

The effect of antipyretics on immune response and fever following receipt of inactivated influenza vaccine in young children.

BACKGROUND: Antipyretics reduce fever following childhood vaccinations; after inactivated influenza vaccine (IIV) they might ameliorate fever and thereby decrease febrile seizure risk, but also possibly blunt the immune response. We assessed the effect of antipyretics on immune responses and fever following IIV in children ages 6 through 47 months. METHODS: Over the course of three seasons, one hundred forty-two children, receiving either a single or the first of 2 recommended doses of IIV, were randomized to receive either oral acetaminophen suspension (n = 59) or placebo (n = 59) (double-blinded) or ibuprofen (n = 24) (open-label) immediately following IIV and every 4-8 h thereafter for 24 h. Blood samples were obtained at enrollment and 4 weeks following the last recommended IIV dose. Responses to IIV were assessed by hemagglutination inhibition assay (HAI). Seroprotection was defined as an HAI titer ≥1:40 and seroconversion as a titer ≥1:40 if baseline titer <1:10 or four-fold rise if baseline titer ≥1:10. Participants were monitored for fever and other solicited symptoms on the day of and day following IIV. RESULTS: Significant differences in seroconversion and post-vaccination seroprotection were not observed between children included in the different antipyretic groups and the placebo group for the vaccine antigens included in IIV over the course of the studies. Frequencies of solicited symptoms, including fever, were similar between treatment groups and the placebo group. CONCLUSIONS: Significant blunting of the immune response was not observed when antipyretics were administered to young children receiving IIV. Studies with larger sample sizes are needed to definitively establish the effect of antipyretics on IIV immunogenicity.