From research to licensure and beyond: clinical development of MenB-FHbp, a broadly protective meningococcal B vaccine

Abstract

Given the characteristics of meningococcal carriage and transmission and the sudden, often severe onset and long-term consequences of disease, vaccination can most effectively provide large-scale control of invasive disease. Six serogroups (A, B, C, W, X, and Y) cause nearly all meningococcal disease globally. Capsular polysaccharide conjugate vaccines can prevent serogroups A, C, W, and Y disease. More recently, recombinant protein vaccines for preventing serogroup B meningococcal (MenB) disease have become available, with a major target of vaccine-induced immune response for both vaccines being bacterial factor H binding protein (FHbp). Importantly, FHbp segregates into only two distinct subfamilies (A [also classified as variants 2 and 3] and B [variant 1]). This review summarizes the complete clinical development program supporting licensure of MenB-FHbp (Trumenba®, Bivalent rLP2086), the only MenB vaccine containing antigens from both FHbp subfamilies. Areas covered: Eleven published clinical studies assessing MenB-FHbp efficacy and safety among 20,803 adolescents and adults are examined. Particular focus is on the methodology of immunogenicity assessments used as a surrogate for clinical efficacy. Expert commentary: Clinical studies in adolescents and adults consistently demonstrated MenB-FHbp safety and induction of immunologic responses against antigenically and epidemiologically diverse MenB isolates, supporting licensure and immunization recommendations.

Meningococcal factor H binding protein as immune evasion factor and vaccine antigen

“…The MenB-fHbp is a bivalent formulation including two lipidated forms of fHbp belonging to families A and B [58]: fHbp subfamily A05 (corresponding to variant 3.45) and subfamily B01 (corresponding to variant 1.55) adjuvanted with aluminum phosphate. This vaccine has been licensed, with the trade name of Trumenba, in the United States in 2014, in Europe in 2017, and more recently in Australia and Canada [59], for use in adolescents and young adults (10-25 years) (https://www. ema.europa.eu/en/documents/overview/trumenba-epa r-summary-public_en.pdf).…”

Immunogenicity of trimeric autotransporter adhesins and their potential as vaccine targets

“…Later, the recombinant protein vaccine MenB-FHbp was licensed in the USA (2014) and the EU (2018). It contains two variants of the meningococcal surface protein factor H-binding protein (FHbp) [58,109].…”

A physician’s guide to the 2-dose schedule of MenB-FHbp vaccine

“…The immunogenicity and safety of MenB-FHbp has thus far been evaluated in 11 published clinical studies wherein more than 15,000 adolescents and young adults received the vaccine. 35 These studies evaluated 2-and 3-dose schedules, long-term immunogenicity, booster dose responses, and coadministration with vaccines commonly given to adolescents, including MenACWY-D, Tdap (Adacel®, Sanofi Pasteur Inc., Swiftwater, PA, USA), 4vHPV (Gardasil®, Merck & Co, Inc., Whitehouse Station, NJ, USA), and Tdap/IPV (Repevax®, Sanofi Pasteur, Lyon, France) vaccines. [36][37][38] Clinical data supporting the MenB-FHbp 2-dose schedule were from a phase 2 randomized clinical study in healthy adolescents aged 11-18 y that evaluated multiple schedules: 2 doses (administered at 0 and 2 months, 0 and 4 months, or 0 and 6 months) or 3 doses (at 0, 1, and 6 months or 0, 2, and 6 months).…”