A phase 4, open-label study to evaluate the safety and immunogenicity of DTaP5-HBV-IPV-Hib in children previously vaccinated with DTaP2-HBV-IPV-Hib or DTaP5-HBV-IPV-Hib (V419-016).

DTaP5-HBV-IPV-Hib (Vaxelis®) is a hexavalent combination vaccine (HV) indicated in infants and toddlers for the prevention of diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive disease due to Haemophilus influenzae type b. Switching between HVs during the childhood vaccination series is sometimes necessary due to, for example, vaccine availability, health-care provider preference, and/or tender awards. The purpose of this study was to describe the safety, tolerability, and immunogenicity of a booster dose of Vaxelis® in participants who previously received a primary infant series of either DTaP2-HBV-IPV-Hib (Hexyon®) or Vaxelis®. Healthy participants approximately 11-13 months of age who previously received a two-dose primary series of Hexyon® (HHV group) or Vaxelis® (VVV group) all received a Vaxelis® booster dose. Immunogenicity was evaluated by measuring antibody levels to individual vaccine antigens approximately 30 days following booster vaccination. Safety was evaluated as the proportion of participants with adverse events (AEs). The proportions of participants with antibody-specific responses for antigens contained in both Vaxelis® and Hexyon® at 30 days post-toddler-booster vaccination with Vaxelis® were comparable between groups, and higher in the VVV group for Vaxelis® antigens PRN and FIM2/3. The overall proportions of participants with AEs were generally comparable between groups. Following a booster dose of Vaxelis®, immune responses were comparable between groups for all shared antigens, and higher in the VVV group for antigens found only in Vaxelis®. The booster was well tolerated in both groups. These data support the use of Vaxelis® as a booster in mixed HV regimens.

Characterization of the cytokine immune response in children who have experienced an episode of typical hemolytic-uremic syndrome.

The lipopolysaccharide (LPS) of enterohemorrhagic Escherichia coli (EHEC) and Shiga toxin together substantially contribute to the pathophysiology of typical hemolytic-uremic syndrome (HUS). Both factors have been shown to be immune stimulators and could play a key role in the individual innate immune response, characterized by proinflammatory and anti-inflammatory cytokines. By use of a whole blood stimulation model, we therefore compared the LPS- and superantigen-induced cytokine responses in children who had been having recovering from an acute episode of typical HUS for at least 6 months (group 1) with those in controls, who consisted of patients seen in the pediatric neurology outpatient department for routine examination (group 2). Samples were analyzed for cytokine protein levels and the levels of mRNA production. LPS stimulation revealed lower levels of interleukin 10 (IL-10) (P < 0.05) and increased levels of gamma interferon (P < 0.05) and increased ratios of pro- and anti-inflammatory cytokines (P < 0.05 for the IL-1beta/IL-10 ratio; P < 0.05 for the tumor necrosis factor alpha/IL-10 ratio) in group 1. In addition superantigen stimulation showed decreased IL-2 levels in group 1 (P < 0.01). Our results suggest an alteration of the cytokine response characterized by high proinflammatory cytokine levels and low anti-inflammatory cytokine levels as well as low levels of IL-2 production in children who have experienced an episode of typical HUS. We hypothesize that this altered immune response is not a residual effect of the infection but a preexisting characteristic of the patient. This could be one reason why individuals infected with EHEC are potentially predisposed to a systemic disease (HUS).