A randomized, phase 1/2 trial of the safety, tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants
Por:
Martinon-Torres F, Gimenez-Sanchez F, Bernaola-Iturbe E, Diez-Domingo J, Jiang Q and Perez JL
Publicada:
8 sep 2014
Resumen:
Background: 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.
Methods: 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-mu g 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.
Results: 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-mu g rLP2086 dose, respectively. Most fevers were <39.0 degrees C. Only 2 subjects in the 20-mu g group and 1 subject in the 60-mu g group experienced fevers >39.0 degrees C; no fevers were >40.0 degrees 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-mu g dose.
Conclusion: Due to the high fever rate experienced in the 20- and 60-mu g groups, rLP2086 in the current formulation may not be acceptable for infants. (C) 2014 Published by Elsevier Ltd.
Filiaciones:
Martinon-Torres F:
Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
Gimenez-Sanchez F:
Complejo Hospitalario Torrecárdenas, Almería, Spain
Bernaola-Iturbe E:
Hospital Virgen del Camino, Pamplona, Spain
:
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
Jiang Q:
Pfizer Vaccine Research, Collegeville, PA, USA
Perez JL:
Pfizer Vaccine Research, Collegeville, PA, USA
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