A phase 1, randomized, open-label, active-controlled trial to assess the safety of a meningococcal serogroup B bivalent rLP2086 vaccine in healthy adults

Abstract

Neisseria meningitidis serogroup B (MnB) is a significant cause of invasive meningococcal disease, but no broadly protective vaccine is yet approved. We assessed the safety and immunogenicity of a bivalent MnB vaccine composed of lipidated subfamily A and B variants of recombinant LP2086 (rLP2086, also known as factor H binding protein, fHBP). Forty-eight adults, ages 18–40 y, were randomized to receive 60, 120 or 200 μg of the bivalent rLP2086 vaccine or control at 0, 2 and 6 mo. Immunogenicity was assessed by rLP2086-specific immunoglobulin G (IgG) geometric mean titers for subfamily A and B proteins. Safety was determined by laboratory assessments of blood and urine and by reporting of solicited and unsolicited adverse events (AEs). The bivalent rLP2086 vaccine elicited high IgG titers following the second and third vaccination at all dose levels. In each of the four study arms, 11 of the 12 participating subjects reported ≥ 1 AE, and no serious AEs were reported. Local and systemic reactions were mainly mild to moderate. Laboratory abnormalities (including increased sodium, decreased neutrophils, and proteinuria) were not associated with clinical events and were not considered to be related to the study vaccine. Vaccinations were generally well-tolerated. Strong IgG antibody responses and the absence of clinically significant laboratory abnormalities support further development of the bivalent rLP2086 vaccine (www.clinicaltrials.gov; identifier: NCT00879814).

Keywords: :

• Meningococcal vaccines
• bacterial outer membrane proteins
• bactericidal antibodies
• factor H binding protein

Acknowledgments

Editorial/medical writing support was provided by Robert Glover and John Clinton Earnheart at Scientific Strategy Partners and was funded by Pfizer Inc. We thank Annaliesa Anderson, Pfizer, for review of the manuscript. This work was presented in part at the 14th Annual Conference on Vaccine Research in Baltimore, MD, on May 16–18, 2011.

Financial Support

This study was sponsored by Wyeth, which was acquired by Pfizer Inc in October 2009. The sponsor was involved in all study stages, from the study design to the data analysis and preparation of the manuscript. The corresponding author had the final responsibility for the decision to submit the manuscript for publication.

Conflict of Interest

P.C.G., Q.J. and J.L.P. are employees of Pfizer Inc. E.S. and H.S. have no conflicts to report but their institution has received clinical research and grant funding from Wyeth, which was acquired by Pfizer Inc in October 2009. Financial compensation was not provided to E.S. or H.S. for manuscript preparation or for participation in the study reported herein.