Immunogenicity and safety of different schedules of the meningococcal ABCWY vaccine, with assessment of long-term antibody persistence and booster responses - results from two phase 2b randomized trials in adolescents

Timo Vesikari; Jerzy Brzostek; Anitta Ahonen; Marita Paassilta; Ewa Majda-Stanislawska; Leszek Szenborn; Miia Virta; Robert Clifford; Teresa Jackowska; Murray Kimmel; Ilaria Bindi; Pavitra Keshavan; Paola Pedotti; Daniela Toneatto

doi:10.1080/21645515.2021.1968214

Immunogenicity and safety of different schedules of the meningococcal ABCWY vaccine, with assessment of long-term antibody persistence and booster responses - results from two phase 2b randomized trials in adolescents

Hum Vaccin Immunother. 2021 Nov 2;17(11):4689-4700. doi: 10.1080/21645515.2021.1968214. Epub 2021 Sep 28.

Authors

Affiliations

¹ Nordic Research Network Oy, Tampere, Finland.
² Health Care Establishment in Debica, Infectious Diseases Outpatient Clinic, Debica, Poland.
³ Vaccine Research Center, Tampere University, Tampere, Finland.
⁴ Tampere University and Tampere University Hospital, Tampere, Finland.
⁵ Department of Pediatric Infectious Diseases, Medical University of Lodz, Lodz, Poland.
⁶ Department of Pediatric Infectious Diseases, Wroclaw Medical University, Wroclaw, Poland.
⁷ Coastal Pediatric Research, Charleston, SC, USA.
⁸ Department of Pediatrics, The Medical Centre of Postgraduate Education, Warsaw, Poland.
⁹ Optimal Research LLC, Melbourne, FL, USA.
¹⁰ Gsk, Siena, Italy.
¹¹ Gsk, Amsterdam, The Netherlands.

Abstract

The meningococcal serogroup B (MenB) protein vaccine, 4CMenB, combined with MenA, MenC, MenW and MenY polysaccharide-protein conjugates for a pentavalent MenABCWY vaccine, can potentially protect against most causative agents of invasive meningococcal disease worldwide. Two phase 2b, randomized, multicenter studies were conducted (NCT02212457, NCT02946385) to assess the immunogenicity and safety of the MenABCWY vaccine as well as antibody persistence and response to a booster dose 2 years after the last vaccination, compared to 4CMenB vaccination. Participants (10 - 18 years), randomized (3:3:2:2:2:2), received the 4-component 4CMenB vaccine according to a 0-2 month (M) schedule or MenABCWY according to a 0-2, 0-6, 0-2-6, 0-1, or 0-11 M schedule. All participants received 5 injections (at M0, M1, M2, M6 and M12) with either the study vaccines or placebo/hepatitis A vaccine. Follow-on participants (4CMenB-0-2, MenABCWY-0-2, MenABCWY-0-6 and MenABCWY-0-2-6 groups) received one dose of either 4CMenB (4CMenB-0-2 group) or MenABCWY and newly enrolled, age-matched, meningococcal vaccine-naïve adolescents (randomized 1:1) received 2 doses (0-2 M) of either 4CMenB or MenABCWY. MenABCWY vaccination was immunogenic against MenB test strains. Non-inferiority for all 4 components of the 4CMenB vaccine could not be demonstrated for the 0-2 M schedule. Antibodies persisted up to 2 years post-MenABCWY vaccination and a booster dose induced an anamnestic response as higher titers were observed in follow-on participants compared to the first-dose response in vaccine-naïve participants. MenABCWY had a clinically-acceptable safety profile, not different from that of 4CMenB.

Keywords: MenABCWY vaccine; adolescents; booster; non-inferiority; persistence.

Publication types

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

MeSH terms

Adolescent
Antibodies, Bacterial
Humans
Immunogenicity, Vaccine
Meningococcal Infections* / prevention & control
Meningococcal Vaccines* / adverse effects
Neisseria meningitidis, Serogroup B*
Randomized Controlled Trials as Topic

Substances

Antibodies, Bacterial
Meningococcal Vaccines

Grants and funding

Novartis Vaccines and Diagnostics Inc., now part of the GSK group of companies provided financial support for the conduct of the primary study. The extension study was funded by GlaxoSmithKline Biologicals SA. All costs associated with the manuscript development were covered by GlaxoSmithKline Biologicals SA.