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Immunogenicity and safety of the quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) in splenectomized or hyposplenic children and adolescents: Results of a phase III, open, non-randomized study.
Vaccine. 2018 04 19; 36(17):2356-2363.V

Abstract

BACKGROUND

Individuals with functional or anatomic asplenia are at high risk for meningococcal disease. We evaluated the immunogenicity and safety of 1 and 2 doses of the quadrivalent meningococcal serogroups A, C, W, Y tetanus toxoid-conjugate vaccine (MenACWY-TT) in this high-risk population.

METHODS

This phase III, open-label, controlled, non-randomized study (NCT01641042) enrolled 1-17-year-olds with impaired splenic activity (high-risk group) and age-matched healthy controls (control group). We measured immune responses to MenACWY-TT by serum bactericidal activity assays using rabbit (rSBA) and human (hSBA) complement and in terms of antibodies against polysaccharides of the 4 vaccine serogroups. We evaluated vaccine response rates (VRRs) as 4-fold increases from pre-vaccination levels or titers ≥1:32 (rSBA)/≥1:8 (hSBA). We recorded solicited and unsolicited adverse events (AEs) during 4 and 31 days post-vaccination, and serious AEs (SAEs) and new onset of chronic illnesses (NOCIs) throughout the study.

RESULTS

The according-to-protocol cohort for immunogenicity included 40 participants per group. In both groups, the first MenACWY-TT dose induced rSBA VRRs of 92.5-100% and hSBA VRRs of 55.6-77.1% across vaccine serogroups. Following the second MenACWY-TT dose, all participants had high responses, with rSBA and hSBA VRRs of 73.0-100% across vaccine serogroups. rSBA and hSBA geometric mean titers for each serogroup increased in both groups (with different magnitudes, but ≥13.1-fold) compared with baseline levels. Polysaccharide antibody concentrations ≥2.0 μg/ml were detected in ≥84.4% of participants and were similar between groups. Incidences of solicited and unsolicited AEs were comparable between groups. We recorded SAEs in 4/43 participants in the high-risk group and 1/43 participants in the control group (none vaccine-related). No NOCIs were reported.

CONCLUSION

In this descriptive study, MenACWY-TT induced similar functional and humoral immune responses and had a clinically acceptable safety profile in children and adolescents with impaired splenic activity and in healthy controls.

Authors+Show Affiliations

Kaiser Permanente Vaccine Study Center, 1 Kaiser Plaza, 16th Floor, Oakland, CA 94612, United States. Electronic address: Nicola.Klein@kp.org.Clinic of Children's Infectious Diseases, Černopolní 212/9, 662 63 Brno, Czech Republic. Electronic address: habanec.tomas@fnbrno.cz.Department of Infectious Diseases, University Hospital, Charles University in Prague, Sokolska 581, 500 05 Hradec Kralove, Czech Republic. Electronic address: Kosinpav@seznam.cz.Department of Medicine, Duke University School of Medicine, Durham, NC 27703, United States. Electronic address: nirmish.shah@duke.edu.GSK, 5, Embassy Links, SRT Road, Opp to Accenture, Cunningham Road, Vasanth Nagar, Bangalore, Karnataka 560052, India. Electronic address: devayani2000in@yahoo.co.in.GSK, 14200 Shady Grove Road, Rockville, MD 20850, United States. Electronic address: jacqueline.m.miller@gsk.com.Chiltern International for GSK, Avenue Fleming 20 (W23), 1300 Wavre, Belgium. Electronic address: mhezareh@yahoo.com.GSK, Avenue Fleming 20 (W23), 1300 Wavre, Belgium. Electronic address: marie.x.van-der-wielen@gsk.com.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29576307

Citation

Klein, Nicola P., et al. "Immunogenicity and Safety of the Quadrivalent Meningococcal ACWY-tetanus Toxoid Conjugate Vaccine (MenACWY-TT) in Splenectomized or Hyposplenic Children and Adolescents: Results of a Phase III, Open, Non-randomized Study." Vaccine, vol. 36, no. 17, 2018, pp. 2356-2363.
Klein NP, Habanec T, Kosina P, et al. Immunogenicity and safety of the quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) in splenectomized or hyposplenic children and adolescents: Results of a phase III, open, non-randomized study. Vaccine. 2018;36(17):2356-2363.
Klein, N. P., Habanec, T., Kosina, P., Shah, N. R., Kolhe, D., Miller, J. M., Hezareh, M., & Van der Wielen, M. (2018). Immunogenicity and safety of the quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) in splenectomized or hyposplenic children and adolescents: Results of a phase III, open, non-randomized study. Vaccine, 36(17), 2356-2363. https://doi.org/10.1016/j.vaccine.2018.02.085
Klein NP, et al. Immunogenicity and Safety of the Quadrivalent Meningococcal ACWY-tetanus Toxoid Conjugate Vaccine (MenACWY-TT) in Splenectomized or Hyposplenic Children and Adolescents: Results of a Phase III, Open, Non-randomized Study. Vaccine. 2018 04 19;36(17):2356-2363. PubMed PMID: 29576307.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunogenicity and safety of the quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) in splenectomized or hyposplenic children and adolescents: Results of a phase III, open, non-randomized study. AU - Klein,Nicola P, AU - Habanec,Tomas, AU - Kosina,Pavel, AU - Shah,Nirmish R, AU - Kolhe,Devayani, AU - Miller,Jacqueline M, AU - Hezareh,Marjan, AU - Van der Wielen,Marie, Y1 - 2018/03/22/ PY - 2017/07/19/received PY - 2018/02/19/revised PY - 2018/02/20/accepted PY - 2018/3/27/pubmed PY - 2018/9/12/medline PY - 2018/3/27/entrez KW - Asplenia KW - Immunogenicity KW - Meningococcal disease KW - Meningococcal vaccine KW - Neisseria meningitidis KW - Safety SP - 2356 EP - 2363 JF - Vaccine JO - Vaccine VL - 36 IS - 17 N2 - BACKGROUND: Individuals with functional or anatomic asplenia are at high risk for meningococcal disease. We evaluated the immunogenicity and safety of 1 and 2 doses of the quadrivalent meningococcal serogroups A, C, W, Y tetanus toxoid-conjugate vaccine (MenACWY-TT) in this high-risk population. METHODS: This phase III, open-label, controlled, non-randomized study (NCT01641042) enrolled 1-17-year-olds with impaired splenic activity (high-risk group) and age-matched healthy controls (control group). We measured immune responses to MenACWY-TT by serum bactericidal activity assays using rabbit (rSBA) and human (hSBA) complement and in terms of antibodies against polysaccharides of the 4 vaccine serogroups. We evaluated vaccine response rates (VRRs) as 4-fold increases from pre-vaccination levels or titers ≥1:32 (rSBA)/≥1:8 (hSBA). We recorded solicited and unsolicited adverse events (AEs) during 4 and 31 days post-vaccination, and serious AEs (SAEs) and new onset of chronic illnesses (NOCIs) throughout the study. RESULTS: The according-to-protocol cohort for immunogenicity included 40 participants per group. In both groups, the first MenACWY-TT dose induced rSBA VRRs of 92.5-100% and hSBA VRRs of 55.6-77.1% across vaccine serogroups. Following the second MenACWY-TT dose, all participants had high responses, with rSBA and hSBA VRRs of 73.0-100% across vaccine serogroups. rSBA and hSBA geometric mean titers for each serogroup increased in both groups (with different magnitudes, but ≥13.1-fold) compared with baseline levels. Polysaccharide antibody concentrations ≥2.0 μg/ml were detected in ≥84.4% of participants and were similar between groups. Incidences of solicited and unsolicited AEs were comparable between groups. We recorded SAEs in 4/43 participants in the high-risk group and 1/43 participants in the control group (none vaccine-related). No NOCIs were reported. CONCLUSION: In this descriptive study, MenACWY-TT induced similar functional and humoral immune responses and had a clinically acceptable safety profile in children and adolescents with impaired splenic activity and in healthy controls. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/29576307/Immunogenicity_and_safety_of_the_quadrivalent_meningococcal_ACWY_tetanus_toxoid_conjugate_vaccine__MenACWY_TT__in_splenectomized_or_hyposplenic_children_and_adolescents:_Results_of_a_phase_III_open_non_randomized_study_ DB - PRIME DP - Unbound Medicine ER -