The only fever resulting in medical attention was for the subject with aseptic meningitis. Nineteen unsolicited AEs were reported among 12 subjects (7 in the 20-μg group, 2 in the 60-μg group, and 3 in the control group), most

of which were related to infection. Seven serious AEs were reported by 5 subjects, none of which were vaccine related: 4 subjects in the 20-μg group had bronchitis (2 cases in same subject), urinary tract infection (2 cases), viral infection, and respiratory syncytial virus bronchiolitis; and 1 subject in the 60-μg group had aseptic meningitis; 2 subjects were withdrawn CH5424802 from the study owing to AEs, neither of which were study related (aseptic meningitis and urinary tract infection; Table 1). OSI744 Although local reactions were generally mild or moderate and AEs were infrequent, fever rates ranged from 63% to 90% in infants receiving one rLP2086 dose. Most fevers were ≤39.0 °C, with only 2 subjects in the 20-μg group and 1 subject in the 60-μg group experiencing fever >39.0 °C; no reported cases were >40.0 °C. Despite the fact that almost 80% of fevers were mild and no cases of severe fever occurred in the 43 trial participants, the high overall fever rate experienced in the 60-μg group suggests that rLP2086 in the current formulation is

not acceptable for infants. Similar to the study presented herein, reactogenicity of the 4CMenB vaccine, Novartis’s fHBP-based MnB vaccine currently licensed in European Union, Canada, and Australia,

was also examined in infants. Interestingly, fever rates were similar to those observed in the present study [16] and [17]. For example, in the most recent phase 3 study of 4CMenB administered with routine vaccination in infants, 65% (1612/2468) of subjects experienced fevers ≥38.5 °C; fevers ≥40 °C occurred in 1% (29/2468) of subjects [17]. It is possible that the OMV component of 4CMenB contributes at least some of the reactogenicity of this vaccine, as an OMV meningococcal B vaccine (MenNZB) developed to target a specific epidemic strain of MnB in New Zealand also elicited fever rates in infants up to 45% at any L-NAME HCl dose, 8% of which were ≥39 °C; analgesic use was reported for up to 67% of subjects at any dose [18]; another study of MenNZB in infants in New Zealand showed similar results [19]. However, without a head-to-head trial, direct comparison of the reactogenicity of 4CMenB and the bivalent rLP2086 vaccine in infants is difficult. The question remains as to why bivalent rLP2086 vaccine is not acceptable in infants but is acceptable in other ages, as fevers were rare and generally mild in toddlers (≥18 months of age; 0–31.6%) [15] and adolescents (0–12.5%) [10] and [11] when administering a 20- or 60-μg dose. Studies in mice suggested that the presence of the lipid tail increases immunogenicity of the vaccine, and thus, the lipidated rLP2086 protein was used in the vaccine [5].