Dataset Information

Meningococcal Serogroup B Bivalent rLP2086 Vaccine Elicits Broad and Robust Serum Bactericidal Responses in Healthy Adolescents.

ABSTRACT:

Background

Neisseria meningitidis serogroup B (MnB) is a leading cause of invasive meningococcal disease in adolescents and young adults. A recombinant factor H binding protein (fHBP) vaccine (Trumenba(®); bivalent rLP2086) was recently approved in the United States in individuals aged 10-25 years. Immunogenicity and safety of 2- or 3-dose schedules of bivalent rLP2086 were assessed in adolescents.

Methods

Healthy adolescents (11 to <19 years) were randomized to 1 of 5 bivalent rLP2086 dosing regimens (0,1,6-month; 0,2,6-month; 0,2-month; 0,4-month; 0,6-month). Immunogenicity was assessed by serum bactericidal antibody assay using human complement (hSBA). Safety assessments included local and systemic reactions and adverse events.

Results

Bivalent rLP2086 was immunogenic when administered as 2 or 3 doses; the most robust hSBA responses occurred with 3 doses. The proportion of subjects with hSBA titers ≥1:8 after 3 doses ranged from 91.7% to 95.0%, 98.9% to 99.4%, 88.4% to 89.0%, and 86.1% to 88.5% for MnB test strains expressing vaccine--heterologous fHBP variants A22, A56, B24, and B44, respectively. After 2 doses, responses ranged from 90.8% to 93.5%, 98.4% to 100%, 69.1% to 81.1%, and 70.1% to 77.5%. Geometric mean titers (GMTs) were highest among subjects receiving 3 doses and similar between the 2- and 3-dose regimens. After 2 doses, GMTs trended numerically higher among subjects with longer intervals between the first and second dose (6 months vs 2 and 4 months). Bivalent rLP2086 was well tolerated.

Conclusions

Bivalent rLP2086 was immunogenic and well tolerated when administered in 2 or 3 doses. Three doses yielded the most robust hSBA response rates against MnB strains expressing vaccine-heterologous subfamily B fHBPs.

SUBMITTER: Vesikari T

PROVIDER: S-EPMC5407127 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

Meningococcal Serogroup B Bivalent rLP2086 Vaccine Elicits Broad and Robust Serum Bactericidal Responses in Healthy Adolescents.

Vesikari Timo T Østergaard Lars L Diez-Domingo Javier J Wysocki Jacek J Flodmark Carl-Erik CE Beeslaar Johannes J Eiden Joseph J Jiang Qin Q Jansen Kathrin U KU Jones Thomas R TR Harris Shannon L SL O'Neill Robert E RE York Laura J LJ Crowther Graham G Perez John L JL

Journal of the Pediatric Infectious Diseases Society 20150804 2

<h4>Background</h4>Neisseria meningitidis serogroup B (MnB) is a leading cause of invasive meningococcal disease in adolescents and young adults. A recombinant factor H binding protein (fHBP) vaccine (Trumenba(®); bivalent rLP2086) was recently approved in the United States in individuals aged 10-25 years. Immunogenicity and safety of 2- or 3-dose schedules of bivalent rLP2086 were assessed in adolescents.<h4>Methods</h4>Healthy adolescents (11 to <19 years) were randomized to 1 of 5 bivalent rL ...[more]

PMID: 26407272

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Project description:BackgroundMeningococcal epidemics in Sub-Sahara caused by serogroup A strains are controlled by a group A polysaccharide conjugate vaccine. Strains with serogroups C, W and X continue to cause epidemics. Protein antigens in licensed serogroup B vaccines are shared among serogroup B and non-B strains.PurposeCompare serum bactericidal antibody responses elicited by an investigational native outer membrane vesicle vaccine with over-expressed Factor H binding protein (NOMV-FHbp) and a licensed serogroup B vaccine (MenB-4C) against African serogroup A, B, C, W and X strains.MethodsHuman Factor H (FH) transgenic mice were immunized with NOMV-FHbp prepared from a mutant African meningococcal strain containing genetically attenuated endotoxin and a mutant sub-family B FHbp antigen with low FH binding, or with MenB-4C, which contains a recombinant sub-family B FHbp antigen that binds human FH, and three other antigens, NHba, NadA and PorA P1.4, capable of eliciting bactericidal antibody.ResultsThe NOMV-FHbp elicited serum bactericidal activity against 12 of 13 serogroup A, B, W or X strains from Africa, and four isogenic serogroup B mutants with sub-family B FHbp sequence variants. There was no activity against a serogroup B mutant with sub-family A FHbp, or two serogroup C isolates from a recent outbreak in Northern Nigeria, which were mismatched for both PorA and sub-family of the FHbp vaccine antigen. For MenB-4C, NHba was expressed by all 16 African isolates tested, FHbp sub-family B in 13, and NadA in five. However, MenB-4C elicited titers ≥ 1:10 against only one isolate, and against only two of four serogroup B mutant strains with sub-family B FHbp sequence variants.ConclusionsNOMV-FHbp has greater potential to confer serogroup-independent protection in Africa than the licensed MenB-4C vaccine. However, the NOMV-FHbp vaccine will require inclusion of sub-family A FHbp for coverage against recent serogroup C strains causing outbreaks in Northern Nigeria.

Project description:BackgroundMeningococcal infection starts with colonisation of the upper respiratory tract. Mucosal immunity is important for protection against acquisition and subsequent meningococcal carriage. In this study, we assessed salivary antibody levels against meningococcal serogroup A (MenA), W (MenW) and Y (MenY) after vaccination with a quadrivalent MenACWY conjugated vaccine. We also compared salivary meningococcal serogroup C (MenC) antibody levels after monovalent MenC and quadrivalent MenACWY conjugated vaccination.MethodsHealthy participants, who had received MenC conjugate vaccine between 14 months and 3 years of age, received a (booster) MenC or MenACWY vaccination at age 10-15 years. MenA-, MenC-, MenW- and MenY-polysaccharide (PS) specific IgG and IgA levels in saliva and serum and PS specific secretory component levels in saliva were measured using the fluorescent-bead-based multiplex immunoassay.ResultsMenACYW vaccination increased salivary PS-specific IgA (2-fold) and IgG levels(>10-fold) for MenA, MenY, and MenW. After one year, salivary IgA levels had returned to baseline levels. Both vaccines induced an increase in salivary MenC-PS specific IgA (>3-fold) and IgG (>100-fold), with higher levels after MenC as compared to MenACWY vaccination. The antibody decay rate of MenC in saliva between one month and one year was similar for both vaccines. The overall correlation between serum and saliva IgA levels was low (R = 0.39, R = 0.58, R = 0.31, and R = 0.36 for MenA, MenC, MenW and MenY, respectively). Serogroup-PS specific IgG levels between serum and saliva correlated better (R ranged from 0.51 to 0.88).ConclusionsBoth primary (MenA, MenY, and MenW) and booster (MenC) parenteral meningococcal conjugate vaccination induced high salivary antibody levels. The strong correlation for MenC, MenW and MenY between saliva and serum IgG levels indicates that saliva might be used as a reliable tool to measure vaccine responses after both primary and booster meningococcal vaccination.

Dataset Information

Meningococcal Serogroup B Bivalent rLP2086 Vaccine Elicits Broad and Robust Serum Bactericidal Responses in Healthy Adolescents.

Background

Methods

Results

Conclusions

Publications

Meningococcal Serogroup B Bivalent rLP2086 Vaccine Elicits Broad and Robust Serum Bactericidal Responses in Healthy Adolescents.

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