Sex, Age, and Race Effects on Immunogenicity of MenB-FHbp, A Bivalent Meningococcal B Vaccine: Pooled Evaluation of Clinical Trial Data

Johannes Beeslaar, Paula Peyrani, Judith Absalon, Jason Maguire, Joseph Eiden, Paul Balmer, Roger Maansson, John L Perez, Johannes Beeslaar, Paula Peyrani, Judith Absalon, Jason Maguire, Joseph Eiden, Paul Balmer, Roger Maansson, John L Perez

Abstract

Introduction: An extensive clinical development program showed that the meningococcal serogroup B-factor H binding protein (MenB-FHbp) vaccine affords protection against MenB disease for adolescents and adults. Data were pooled from multiple studies within the program to examine whether MenB-FHbp immunogenicity was influenced by sex, age, or race.

Methods: Immunogenicity was assessed in subjects from seven studies who received 120 µg MenB-FHbp (at 0, 2, 6 months) and had evaluated immune responses against four representative test strains via serum bactericidal assays using human complement (hSBAs). Immune responses were presented by sex (male, female), age group (10-14, 15-18, 19-25, 10-25 years), and race (white, black, Asian, other).

Results: Among 8026 subjects aged 10-25 years included in this analysis, MenB-FHbp elicited robust immune responses in a high percentage of subjects regardless of demographic characteristics. Across all test strains and demographic subsets, a ≥ 4-fold rise in titer from baseline was achieved in 76.7-95.0% of subjects, with no major differences by sex, age groups assessed, or races evaluated. Corresponding percentages achieving titers ≥ the lower limit of quantification (LLOQ) against all four strains combined were 79.7-87.3% (sex), 81.6-85.5% (age), and 80.0-88.1% (race). Minor differences were observed for geometric mean titers and percentages of subjects achieving titers ≥ LLOQ against each strain based on demographics.

Conclusion: These data suggested no clinically meaningful differences in MenB-FHbp immunogenicity when administered as a three-dose schedule based on sex, ages assessed, or races evaluated. This analysis supports the continued recommended use of MenB-FHbp to prevent MenB disease in adolescents and young adults.

Trial registration: ClinicalTrials.gov identifiers, NCT00808028, NCT01830855, NCT01323270, NCT01461993, NCT01461980, NCT01352845, and NCT01299480.

Keywords: Clinical trial; Immunogenicity; Invasive meningococcal disease; Serogroup B; Vaccines.

References

    1. Martinón-Torres F. Deciphering the burden of meningococcal disease: conventional and under-recognized elements. J Adolesc Health. 2016;59:S12–S20.
    1. Centers for Disease Control and Prevention. Enhanced meningococcal disease surveillance report (2017). .
    1. European Centre for Disease Prevention and Control. Surveillance Atlas of Infectious Diseases (2019). . Accessed 3 June 2019.
    1. Balmer P, York LJ. Optimal use of meningococcal serogroup B vaccines: moving beyond outbreak control. Ther Adv Vaccines Immunother. 2018;6:49–60.
    1. Trumenba® (meningococcal group B vaccine). Full Prescribing Information, Wyeth Pharmaceuticals Inc (a subsidiary of Pfizer Inc), Philadelphia; 2018.
    1. Bexsero® (meningococcal group B vaccine). Full Prescribing Information, GSK Vaccines, Srl, Siena; 2018.
    1. Murphy E, Andrew L, Lee KL, et al. Sequence diversity of the factor H binding protein vaccine candidate in epidemiologically relevant strains of serogroup B Neisseria meningitidis. J Infect Dis. 2009;200:379–389.
    1. Ostergaard L, Vesikari T, Absalon J, et al. A bivalent meningococcal B vaccine in adolescents and young adults. N Engl J Med. 2017;347:2349–2362.
    1. Perez JL, Absalon J, Beeslaar J, et al. From research to licensure and beyond: clinical development of MenB-FHbp, a broadly protective meningococcal B vaccine. Expert Rev Vaccines. 2018;17:461–477.
    1. Lord JM. The effect of ageing of the immune system on vaccination responses. Hum Vaccines Immunother. 2013;9:1364–1367.
    1. Demirjian A, Levy O. Safety and efficacy of neonatal vaccination. Eur J Immunol. 2009;39:36–46.
    1. van Werkhoven CH, Huijts SM, Bolkenbaas M, Grobbee DE, Bonten MJ. The impact of age on the efficacy of 13-valent pneumococcal conjugate vaccine in elderly. Clin Infect Dis. 2015;61:1835–1838.
    1. Sow PS, Watson-Jones D, Kiviat N, et al. Safety and immunogenicity of human papillomavirus-16/18 AS04-adjuvanted vaccine: a randomized trial in 10-25-year-old HIV-seronegative African girls and young women. J Infect Dis. 2013;207:1753–1763.
    1. Pedersen C, Petaja T, Strauss G, et al. Immunization of early adolescent females with human papillomavirus type 16 and 18 L1 virus-like particle vaccine containing AS04 adjuvant. J Adolesc Health. 2007;40:564–571.
    1. Flanagan KL, Fink AL, Plebanski M, Klein SL. Sex and gender differences in the outcomes of vaccination over the life course. Annu Rev Cell Dev Biol. 2017;33:577–599.
    1. Jorgensen TN. Sex disparities in the immune response. Cell Immunol. 2015;294:61–62.
    1. Klein SL, Jedlicka A, Pekosz A. The Xs and Y of immune responses to viral vaccines. Lancet Infect Dis. 2010;10:338–349.
    1. Klein SL, Marriott I, Fish EN. Sex-based differences in immune function and responses to vaccination. Trans R Soc Trop Med Hyg. 2015;109:9–15.
    1. Fink AL, Klein SL. Sex and gender impact immune responses to vaccines among the elderly. Physiology (Bethesda) 2015;30:408–416.
    1. Haralambieva IH, Salk HM, Lambert ND, et al. Associations between race, sex and immune response variations to rubella vaccination in two independent cohorts. Vaccine. 2014;32:1946–1953.
    1. Kurupati R, Kossenkov A, Haut L, et al. Race-related differences in antibody responses to the inactivated influenza vaccine are linked to distinct pre-vaccination gene expression profiles in blood. Oncotarget. 2016;7:62898–62911.
    1. Moberley S, Licciardi PV, Balloch A, et al. Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness. Vaccine. 2017;35:2908–2915.
    1. Rager-Zisman B, Bazarsky E, Skibin A, et al. Differential immune responses to primary measles-mumps-rubella vaccination in Israeli children. Clin Diagn Lab Immunol. 2004;11:913–918.
    1. Voysey M, Barker CI, Snape MD, et al. Sex-dependent immune responses to infant vaccination: an individual participant data meta-analysis of antibody and memory B cells. Vaccine. 2016;34:1657–1664.
    1. Muse D, Christensen S, Bhuyan P, et al. A phase 2, randomized, active-controlled, observer-blinded study to assess the immunogenicity, tolerability and safety of bivalent rLP2086, a meningococcal serogroup B vaccine, coadministered with tetanus, diphtheria and acellular pertussis vaccine and serogroup A, C, Y and W-135 meningococcal conjugate vaccine in healthy US adolescents. Pediatr Infect Dis J. 2016;35:673–682.
    1. Richmond PC, Marshall HS, Nissen MD, et al. Safety, immunogenicity, and tolerability of meningococcal serogroup B bivalent recombinant lipoprotein 2086 vaccine in healthy adolescents: a randomised, single-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2012;12:597–607.
    1. Senders S, Bhuyan P, Jiang Q, et al. Immunogenicity, tolerability, and safety in adolescents of bivalent rLP2086, a meningococcal serogroup B vaccine, coadministered with quadrivalent human papilloma virus vaccine. Pediatr Infect Dis J. 2016;35:548–554.
    1. Vesikari T, Ostergaard L, Diez-Domingo J, et al. Meningococcal serogroup B bivalent rLP2086 vaccine elicits broad and robust serum bactericidal responses in healthy adolescents. J Ped Infect Dis Soc. 2015;35:673–682.
    1. Vesikari T, Wysocki J, Beeslaar J, et al. Immunogenicity, safety, and tolerability of bivalent rLP2086 meningococcal group B vaccine administered concomitantly with diphtheria, tetanus, and acellular pertussis and inactivated poliomyelitis vaccines to healthy adolescents. J Pediatr Infect Dis Soc. 2016;5:180–187.
    1. Ostergaard L, Vesikari T, Absalon J, et al. A bivalent meningococcal B vaccine in adolescents and young adults. N Engl J Med. 2017;377:2349–2362.
    1. Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129:1307–1326.
    1. Borrow R, Balmer P, Miller E. Meningococcal surrogates of protection—serum bactericidal antibody activity. Vaccine. 2005;23:2222–2227.
    1. McNeil LK, Donald RGK, Gribenko A, et al. Predicting the susceptibility of meningococcal serogroup B isolates to bactericidal antibodies elicited by bivalent rLP2086, a novel prophylactic vaccine. MBio. 2018;9:e00036-18.
    1. Jiang HQ, Hoiseth SK, Harris SL, et al. Broad vaccine coverage predicted for a bivalent recombinant factor H binding protein based vaccine to prevent serogroup B meningococcal disease. Vaccine. 2010;28:6086–6093.
    1. Belshe RB, Edwards KM, Vesikari T, et al. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med. 2007;356:685–696.
    1. Monto AS, Ohmit SE, Petrie JG, et al. Comparative efficacy of inactivated and live attenuated influenza vaccines. N Engl J Med. 2009;361:1260–1267.
    1. Yang Y, Meng Y, Halloran ME, Longini IM., Jr Dependency of vaccine efficacy on preexposure and age: a closer look at a tetravalent dengue vaccine. Clin Infect Dis. 2018;66:178–184.
    1. Liko J, Robison SG, Cieslak PR. Pertussis vaccine performance in an epidemic year—Oregon, 2012. Clin Infect Dis. 2014;59:261–263.
    1. de Moraes JC, Perkins BA, Camargo MC, et al. Protective efficacy of a serogroup B meningococcal vaccine in Sao Paulo, Brazil. Lancet. 1992;340:1074–1078.
    1. Harder T, Koch J, Wichmann O, Hellenbrand W. Predicted vs observed effectiveness of outer membrane vesicle (OMV) vaccines against meningococcal serogroup B disease: systematic review. J Infect. 2017;75:81–94.
    1. Engler RJ, Nelson MR, Klote MM, et al. Half- vs full-dose trivalent inactivated influenza vaccine (2004–2005): age, dose, and sex effects on immune responses. Arch Intern Med. 2008;168:2405–2414.
    1. Bermal N, Szenborn L, Chrobot A, et al. The 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) coadministered with DTPw-HBV/Hib and poliovirus vaccines: assessment of immunogenicity. Pediatr Infect Dis J. 2009;28:S89–S96.
    1. Knuf M, Szenborn L, Moro M, et al. Immunogenicity of routinely used childhood vaccines when coadministered with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) Pediatr Infect Dis J. 2009;28:S97–S108.
    1. Mariani L, Venuti A. HPV vaccine: an overview of immune response, clinical protection, and new approaches for the future. J Transl Med. 2010;8:105.
    1. Vidal AC, Smith JS, Valea F, et al. HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA. Cancer Causes Control. 2014;25:1055–1062.

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