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We recently found that children who experience recurrent otitis media despite individualized care (stringently-defined otitis prone [sOP]) do not develop an antibody response to several vaccine candidate protein antigens expressed by Streptococcus pneumonia (Spn) and Haemophilus influenzae. Here we sought to determine if these same children also failed to develop antibody to routine pediatric vaccinations.One hundred forty sera collected from children age 6–24 months were analyzed. sOP (n = 34) and age-matched non-sOP (n = 34) children were assessed for IgG concentrations to diphtheria toxoid, tetanus toxoid, pertussis toxoid, filamentous hemagglutinin, pertactin (DTaP), polio, hepatitis B, H. influenzae type b capsule polyribosyl-ribitol-phosphate (PRP) and Spn capsular polysaccharide conjugate vaccine.IgG protective titers to diphtheria toxoid (P = 0.006), tetanus toxoid (P < 0.0001), pertussis toxoid (P < 0.0001), filamentous hemagglutinin (P = 0.001), pertactin (P = 0.005), hepatitis B (P < 0.0001), polio 3 (P = 0.03) and Spn 23F (P = 0.01) but not polio 1,2, PRP or Spn 6B, and 14 were decreased in sOP versus non-sOP children using generalized estimating equations. A high percentage of sOP children had nonprotective antibody values that persisted until 24 months of age despite routine boosters.sOP children may fail to achieve protective antibody concentrations after several routine vaccinations.