title: A randomized, phase 1/2 trial of the safety, tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants.
abstract: Neisseria meningitidis serogroup B (MnB) is a major cause of invasive meningococcal disease in infants. A conserved, surface-exposed lipoprotein, LP2086 (a factor H-binding protein [fHBP]), is a promising MnB vaccine target. A bivalent, recombinant vaccine targeting the fHBP (rLP2086) of MnB was developed.
  
  
  
  This phase 1/2 clinical study was designed to assess the immunogenicity, safety, and tolerability of a 4-dose series of the rLP2086 vaccine at 20-, 60-, 120-, or 200-μg dose levels in vaccine-naive infants when given with routine childhood vaccines. The study was to consist of two phases: a single-blind sentinel phase and an open-label full enrollment phase. During the sentinel phase, randomization of subjects to the next higher dose was delayed pending a 14-day safety review of dose 1 of the preceding dose cohort. The full enrollment phase was to occur after completion of the sentinel phase.
  
  
  
  Local reactions were generally mild and adverse events infrequent; however, after only 46 infants were randomized into the study, fever rates were 64% and 90% in subjects receiving one 20- or 60-μg rLP2086 dose, respectively. Most fevers were <39.0°C. Only 2 subjects in the 20-μg group and 1 subject in the 60-μg group experienced fevers >39.0°C; no fevers were >40.0°C. Due to these high fever rates, the study was terminated early. No immunogenicity data were collected. This report discusses the safety and acceptability of rLP2086 in infants after one 20- or 60-μg dose.
  
  
  
  Due to the high fever rate experienced in the 20- and 60-μg groups, rLP2086 in the current formulation may not be acceptable for infants.
authors: Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
authors: Federico
authors: F
authors: Martinon-Torres
authors: Complejo Hospitalario Torrecárdenas, Almería, Spain.
authors: Francisco
authors: F
authors: Gimenez-Sanchez
authors: Hospital Virgen del Camino, Pamplona, Spain.
authors: Enrique
authors: E
authors: Bernaola-Iturbe
authors: Área de Investigación en Vacunas, Centro Superior de Investigación en Salud Pública (CSISP), Valencia, Spain; Vaccine Research Unit, Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
authors: Javier
authors: J
authors: Diez-Domingo
authors: Pfizer Vaccine Research, Collegeville, PA, USA.
authors: Qin
authors: Q
authors: Jiang
authors: Pfizer Vaccine Research, Collegeville, PA, USA. Electronic address: john.perez@pfizer.com.
authors: John L
authors: JL
authors: Perez
mesh_terms: D064420:Drug-Related Side Effects and Adverse Reactions; D057239:Early Termination of Clinical Trials; D005260:Female; D005334:Fever / Q000139:chemically induced*; D006801:Humans; D007223:Infant; D008297:Male; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000009:adverse effects* / Q000627:therapeutic use; D038541:Neisseria meningitidis, Serogroup B; D016037:Single-Blind Method; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D022401:Meningococcal Vaccines; D014614:Vaccines, Synthetic
keywords: Factor H-binding protein; Infants; LP2086; Neisseria meningitidis serogroup B