Immunogenicity and safety of the diphtheria, pertussis, tetanus and inactivated poliovirus vaccine when co-administered with the human rotavirus vaccine (Rotarix) in healthy Japanese infants: a phase IV randomized study.

Rotavirus infections have been reported to account for 40-50% of all hospitalized acute gastroenteritis cases in young children (<5 years) in Japan. Since 2011, Rotarix containing the live attenuated human rotavirus RIX4414 strain (HRV) has been licensed in Japan for infants. Vaccination against rotavirus is optional in Japan whereas administration of diphtheria, pertussis, tetanus, and inactivated poliovirus (DPT-IPV) vaccine is part of the national routine immunization program. In this open-label, randomized, controlled, multicenter study, we evaluated the immunogenicity and safety of the DPT-IPV vaccine (Squarekids) administered concomitantly or staggered with the liquid HRV (Rotarix) vaccine in healthy Japanese infants. A total of 292 infants aged 6-12 weeks were randomly assigned to receive DPT-IPV vaccine and HRV vaccine co-administered (n = 147) or staggered (n = 145). Immune responses to DPT-IPV vaccine were evaluated by measuring the post-vaccination serum antibody titers/concentrations to each antigen at one month following the third dose of DPT-IPV vaccine. Seroprotection/seropositivity against each of the diphtheria, pertussis (pertussis toxin and filamentous hemagglutinin), tetanus, and poliovirus type 1, 2 and 3 antigens was 92.8% or higher in both groups. In terms of immunogenicity, DPT-IPV vaccine co-administered with HRV vaccine was shown to be non-inferior to DPT-IPV vaccine with a staggered administration. The safety profile was comparable in the two vaccine groups with no vaccine-related serious adverse events, no deaths and no cases of intussusception. These results support co-administration of HRV vaccine with DPT-IPV vaccine in Japan. ClinicalTrials.gov NCT02907216.

Potentials of the circulating pruritogenic mediator lysophosphatidic acid in development of allergic skin inflammation in mice: role of blood cell-associated lysophospholipase D activity of autotaxin.

Itching and infiltration of immune cells are important hallmarks of atopic dermatitis (AD). Although various studies have focused on peripheral mediator-mediated mechanisms, systemic mediator-mediated mechanisms are also important in the pathogenesis and development of AD. Herein, we found that intradermal injection of lysophosphatidic acid (LPA), a bioactive phospholipid, induces scratching responses by Institute of Cancer Research mice through LPA1 receptor- and opioid µ receptor-mediating mechanisms, indicating its potential as a pruritogen. The circulating level of LPA in Naruto Research Institute Otsuka Atrichia mice, a systemic AD model, with severe scratching was found to be higher than that of control BALB/c mice, probably because of the increased lysophospholipase D activity of autotaxin (ATX) in the blood (mainly membrane associated) rather than in plasma (soluble). Heparan sulfate proteoglycan was shown to be involved in the association of ATX with blood cells. The sequestration of ATX protein on the blood cells by heparan sulfate proteoglycan may accelerate the transport of LPA to the local apical surface of vascular endothelium with LPA receptors, promoting the hyperpermeability of venules and the pathological uptake of immune cells, aggravating lesion progression and itching in Naruto Research Institute Otsuka Atrichia mice.