A phase 2 open-label safety and immunogenicity study of a meningococcal B bivalent rLP2086 vaccine in healthy adults

Marshall, Helen; Richmond, Peter; Nissen, Michael D.; Wouters, Ann; Baber, James; Jiang, Qin; Anderson, Annaliesa S.; Jones, Thomas R.; Harris, Shannon L.; Jansen, Kathrin U.; Perez, John L.

doi:10.1016/j.vaccine.2013.01.021

Cited by 73 publications

(46 citation statements)

References 24 publications

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“…5. The ability of rLP2086 to induce strong bactericidal immune responses was earlier demonstrated in phase I (n = 48) [32] and phase II (n = 60) [33] trials in healthy adults aged 18-40 years and in a small (n = 13) phase II trial in laboratory personnel (aged 37-62 years) with an occupational risk of exposure to pathogenic N. meningitidis (study B197-1042) [28]. Phase I [34,35] and phase I/II [36] trials conducted using an early rLP2086 formulation in subjects 18-36 months old [34], 8-14 [36], and 18-25 years old [35] also demonstrated the potential for an rLP2086 vaccine to induce strong bactericidal immune responses.…”

Section: Immunogenicity Of Rlp2086mentioning

confidence: 88%

Bivalent rLP2086 Vaccine (Trumenba®): A Review in Active Immunization Against Invasive Meningococcal Group B Disease in Individuals Aged 10–25 Years

Shirley

Dhillon

2015

BioDrugs

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Bivalent rLP2086 vaccine (Trumenba(®)) [hereafter referred to as rLP2086] is a Neisseria meningitidis serogroup B (MenB) vaccine recently licensed in the USA for active immunization to prevent invasive disease caused by MenB in individuals 10-25 years of age. rLP2086, which contains two variants of the meningococcal surface protein factor H-binding protein (fHBP), was approved by the FDA under the accelerated approval pathway after the immunogenicity of the vaccine was demonstrated in several phase II trials. This article reviews the immunogenicity and reactogenicity of rLP2086 as demonstrated in the trials with a focus on the US setting and on use of the vaccine as per FDA-approved labeling. rLP2086 is approved in the USA as a three-dose series administered in a 0-, 2-, and 6-month schedule. In the phase II trials, rLP2086 elicited a robust immune response against a panel of MenB test strains. A strong immune response was evident in a marked proportion of subjects after two vaccine doses, with a further increase after a third dose. The four primary test strains used were selected to be representative of MenB strains prevalent in the USA, with each expressing an fHBP variant heterologous to the vaccine antigens. rLP2086 was generally well tolerated in the trials, with most adverse reactions being mild to moderate in severity. Although some questions remain, including the duration of the protective response, rLP2086 vaccine has the potential to be a valuable tool for the prevention of invasive MenB disease.

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Section: Immunogenicity Of Rlp2086mentioning

confidence: 88%

Bivalent rLP2086 Vaccine (Trumenba®): A Review in Active Immunization Against Invasive Meningococcal Group B Disease in Individuals Aged 10–25 Years

Shirley

Dhillon

2015

BioDrugs

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“…Five heterologous MnB strains were also tested in this study; the response rates after dose 3 ranged from 77 to 100% at the 60-g dose and from 88 to 100% at the 200-g dose. In another study in adults with the final bivalent rLP2086 vaccine at the 120-g dose, the response rates after three doses were 81 to 94%, irrespective of whether the hSBA strain expressed homologous or heterologous fHBP (130). In adolescents and children over the age of 8 years, the response rate after dose 3 at the 200-g dose was 91% for the vaccine homologous strain and ranged from 47 to 98% for vaccine heterologous strains (129).…”

Section: Development Of Fhbp Vaccines For Broad Protection Against Mnmentioning

confidence: 96%

“…Published studies are available that describe the clinical trial results with both the initial (81,128,129) and final (80,130,137) formulations of Pfizer's bivalent rLP2086 vaccine. However, a comprehensive review of clinical findings for Pfizer's bivalent rLP2086 vaccine is not yet available.…”

Section: Development Of Fhbp Vaccines For Broad Protection Against Mnmentioning

confidence: 99%

Role of Factor H Binding Protein in Neisseria meningitidis Virulence and Its Potential as a Vaccine Candidate To Broadly Protect against Meningococcal Disease

McNeil

Zagursky

Lin

et al. 2013

Microbiol Mol Biol Rev

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SUMMARY Neisseria meningitidis is a Gram-negative microorganism that exists exclusively in humans and can cause devastating invasive disease. Although capsular polysaccharide-based vaccines against serogroups A, C, Y, and W135 are widely available, the pathway to a broadly protective vaccine against serogroup B has been more complex. The last 11 years has seen the discovery and development of the N. meningitidis serogroup B (MnB) outer membrane protein factor H binding protein (fHBP) as a vaccine component. Since the initial discovery of fHBP, a tremendous amount of work has accumulated on the diversity, structure, and regulation of this important protein. fHBP has proved to be a virulence factor for N. meningitidis and a target for functional bactericidal antibodies. fHBP is critical for survival of meningococci in the human host, as it is responsible for the primary interaction with human factor H (fH). Binding of hfH by the meningococcus serves to downregulate the host alternative complement pathway and helps the organism evade host innate immunity. Preclinical studies have shown that an fHBP-based vaccine can elicit serum bactericidal antibodies capable of killing MnB, and the vaccine has shown very encouraging results in human clinical trials. This report reviews our current knowledge of fHBP. In particular, we discuss the recent advances in our understanding of fHBP, its importance to N. meningitidis , and its potential role as a vaccine for preventing MnB disease.

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“…The resulting final formulation was used for all subsequent clinical studies including a Phase 1 Study (B1971004) and a Phase 1/2 Study (B1971003) conducted in subjects 18 to 40 y of age, where the final selected dose level of 120 µg (60 µg of rLP2086 variant A05 and 60 µg of rLP2086 variant B01) was confirmed. 33,34 The potential for bivalent rLP2086 to generate broadly Figure 5. Overview of the MeASURe assay.…”

Section: The Clinical Performance Of Bivalent Rlp2086mentioning

confidence: 99%

The Discovery and Development of a Novel Vaccine to Protect againstNeisseria meningitidisSerogroup B Disease

Zlotnick

Jones

Liberator³

et al. 2014

Human Vaccines & Immunotherapeutics

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A phase 2 open-label safety and immunogenicity study of a meningococcal B bivalent rLP2086 vaccine in healthy adults

Cited by 73 publications

References 24 publications

Bivalent rLP2086 Vaccine (Trumenba®): A Review in Active Immunization Against Invasive Meningococcal Group B Disease in Individuals Aged 10–25 Years

Bivalent rLP2086 Vaccine (Trumenba®): A Review in Active Immunization Against Invasive Meningococcal Group B Disease in Individuals Aged 10–25 Years

Role of Factor H Binding Protein in Neisseria meningitidis Virulence and Its Potential as a Vaccine Candidate To Broadly Protect against Meningococcal Disease

The Discovery and Development of a Novel Vaccine to Protect againstNeisseria meningitidisSerogroup B Disease

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