Novel synthetic (poly)glycerolphosphate-based antistaphylococcal conjugate vaccine.

Staphylococcal infections are a major source of global morbidity and mortality. Currently there exists no antistaphylococcal vaccine in clinical use. Previous animal studies suggested a possible role for purified lipoteichoic acid as a vaccine target for eliciting protective IgG to several Gram-positive pathogens. Since the highly conserved (poly)glycerolphosphate backbone of lipoteichoic acid is a major antigenic target of the humoral immune system during staphylococcal infections, we developed a synthetic method for producing glycerol phosphoramidites to create a covalent 10-mer of (poly)glycerolphosphate for potential use in a conjugate vaccine. We initially demonstrated that intact Staphylococcus aureus elicits murine CD4(+) T cell-dependent (poly)glycerolphosphate-specific IgM and IgG responses in vivo. Naive mice immunized with a covalent conjugate of (poly)glycerolphosphate and tetanus toxoid in alum plus CpG-oligodeoxynucleotides produced high secondary titers of serum (poly)glycerolphosphate-specific IgG. Sera from immunized mice enhanced opsonophagocytic killing of live Staphylococcus aureus in vitro. Mice actively immunized with the (poly)glycerolphosphate conjugate vaccine showed rapid clearance of staphylococcal bacteremia in vivo relative to mice similarly immunized with an irrelevant conjugate vaccine. In contrast to purified, natural lipoteichoic acid, the (poly)glycerolphosphate conjugate vaccine itself exhibited no detectable inflammatory activity. These data suggest that a synthetic (poly)glycerolphosphate-based conjugate vaccine will contribute to active protection against extracellular Gram-positive pathogens expressing this highly conserved backbone structure in their membrane-associated lipoteichoic acid.

Immunization Completion in Infants Born at Low Birth Weight.

BACKGROUND: Low birth weight (LBW) has been associated with underimmunization. We sought to understand the effect of LBW on immunization completion after controlling for previously hypothesized mediators, including prematurity, neonatal illness, well-child care, non-well-child visits, and provider consistency. METHODS: We formed a retrospective cohort of infants born between 2008 and 2011 with ≥2 years of military healthcare follow-up. International Classification of Diseases, Ninth Revision codes were used to identify LBW, preterm birth, neonatal illnesses, well-child visits, non-well-child visits, provider consistency, and parental rank in the inpatient and outpatient records. Immunization records were extracted from both records. Logistic regression determined the odds of immunization completion and well-child care completion (ie, having had ≥6 WCC visits by 15 months of age). RESULTS: Of 135964 included infants, 116521 (85.7%) were completely immunized at the age of 2 years. In adjusted analysis, the odds of immunization completion were significantly decreased in infants born at LBW (odds ratio [OR], 0.88 [95% confidence interval (CI), 0.79-0.97]), very LBW (OR, 0.61 [95% CI, 0.48-0.77]), or extremely LBW (OR, 0.45 [95% CI, 0.33-0.63]) or at ≤32 weeks' gestation (OR, 0.76 [95% CI, 0.63-0.92]), infants with chronic lung disease (OR, 0.63 [95% CI, 0.45-0.88]), male infants (OR, 0.96 [95% CI, 0.93-0.99]), and infants who experienced decreased provider consistency (OR, 0.92 [95% CI, 0.91-0.92]). The rate of immunization completion increased with the overall number of healthcare visits (OR, 1.02 [95% CI, 1.02-1.02]) and complete well-child care (OR, 1.80 [95% CI, 1.75-1.86]). However, children born LBW or preterm were significantly less likely to have complete well-child care. CONCLUSIONS: After adjustment for preterm birth, comorbid neonatal conditions, and early childhood patterns of healthcare use, LBW was significantly associated with immunization noncompletion in a universal healthcare system. Provider consistency and well-child care seem important for increasing immunization completion in LBW infants.