A comprehensive review of clinical and real-world safety data for the four-component serogroup B meningococcal vaccine (4CMenB)

ABSTRACT

Introduction

Neisseria meningitidis causes invasive meningococcal disease and, globally, significant morbidity, with serogroup B (MenB) being the most common cause of endemic disease and outbreaks in several regions. Extensive use of the four-component serogroup B meningococcal vaccine (4CMenB; Bexsero, GSK) and its inclusion in immunization programs in several countries have generated substantial safety data during the 9 years since its first authorization in 2013.

Areas covered

4CMenB safety data from clinical trials and post-marketing surveillance studies (2011 to 2022), and spontaneously reported adverse events of medical interest from the GSK global safety database. We discuss these safety findings in relation to the benefit of 4CMenB vaccination and implications for further enhancing vaccine confidence.

Expert opinion

4CMenB has been consistently well tolerated across clinical trials and post-licensure surveillance studies, despite a higher incidence of fever reported in infants than with other pediatric vaccines. Surveillance data have not identified any significant safety issues, consistent with an acceptable safety profile of 4CMenB. These findings highlight the need to balance the risk of relatively common, transient, post-immunization fever with the benefit of affording protection that reduces the risk of uncommon but potentially fatal meningococcal infection.

Plain Language Summary

The four-component serogroup B meningococcal vaccine 4CMenB (Bexsero®, GSK) was licensed in 2013 and has acquired substantial safety evidence through clinical trial and real-world data. Availability of real-world and clinical 4CMenB safety evidence is important to help address vaccination hesitancy. This comprehensive review of safety data, from 9 years of 4CMenB use including recent data from the real world, shows no significant safety issues in a variety of age groups. Data show that transient fever may occur after vaccination. Invasive meningococcal disease, although rare, can be life-threatening. Abundant safety data from this review can help reassure individuals and healthcare providers on the use of 4CMenB.

KEYWORDS:

• 4CMenB
• clinical trials
• meningococcal serogroup B vaccine
• safety
• surveillance

Article highlights

• We carried out a comprehensive review of safety data from 9 years of 4CMenB use, including safety reported in clinical trials, post-marketing surveillance studies, and spontaneously reported adverse events of medical interest from the GSK safety database.

• 4CMenB was well tolerated across clinical trials and surveillance studies despite a higher incidence of transient fever in infants than seen with other pediatric vaccines.

• Surveillance data have not identified any significant safety issues in a variety of age groups, and are consistent with the known safety profile of 4CMenB.

• Invasive meningococcal disease, although rare, can be life-threatening. The data from this review should help to reassure patients and healthcare providers about the acceptable safety profile of 4CMenB.

Abbreviations

4CMenB	=	Four-component serogroup B meningococcal vaccine
AE	=	Adverse event
BC	=	Brighton Collaboration
BL	=	Baseline
CI	=	Confidence interval
DTaP	=	Diphtheria-tetanus-acellular pertussis
GP	=	General practitioner
GSKMQ	=	GSK MedDRA Query
Hib	=	Haemophilus influenzae type b
ic	=	Intercalated
IMD	=	Invasive meningococcal disease
IPV	=	Inactivated polio
MedDRA	=	Medical Dictionary for Regulatory Activities
MenACWY-CRM	=	Quadrivalent serogroups A, C, W, Y-cross-reactive material 197 conjugate meningococcal vaccine
MenB	=	Meningococcal serogroup B
MenC	=	Meningococcal serogroup C
MMRV	=	Measles-mumps-rubella-varicella
ND	=	Not determined
NIP	=	National immunization program
OMV	=	Outer membrane vesicle
PCV	=	Pneumococcal conjugate vaccine
PMS	=	Post-marketing surveillance
PRR	=	Proportional reporting ratio
PT	=	Preferred terms
rMenB	=	Serogroup B meningococcal vaccine incorporating recombinant antigens
RV	=	Routine vaccines
SAE	=	Serious adverse event
SIDS	=	Sudden infant death syndrome
SMQ	=	Standard MedDRA query
THIN	=	The Health Improvement Network
WHO	=	World Health Organization

Acknowledgments

The authors thank Daniela Toneatto for her valued input and OPEN Health Communications (London, UK) for editorial assistance in the preparation of this manuscript, with financial support from GSK. This work has been presented in part at the European Society for Paediatric Infectious Diseases (ESPID) Annual Meeting 2023; 8–12 May 2023; Lisbon, Portugal and Online.

Declaration of interest

WY Sohn, R Bekkat-Berkani, A Banzhoff, S Cenci, and V Abbing-Karahagopian are employees of the GSK group of companies and hold shares in the GSK group of companies as part of their employee remuneration. E Occhipinti is an employee of the GSK group of companies. G S Marshall has received consulting fees from GSK, Merck, Moderna, Pfizer, Sanofi, and Seqirus, and the University of Louisville has received contracts for vaccine clinical trials sponsored by GSK, Merck, Pfizer, Sanofi, and Seqirus, where G S Marshall was an investigator. H S Marshall is an investigator on investigational vaccine trials sponsored by Novartis, Pfizer, and Iliad. Her institution has received funding from industry, including GSK, Pfizer, and Sanofi-Pasteur for investigator-led vaccine research. She does not receive any personal payments from industry. J H Conway has received consulting fees from GSK, Merck, Moderna, Pfizer, and the University of Wisconsin, and has received contracts for vaccine clinical trials sponsored by Moderna, GSK, Sanofi, and AstraZeneca, where J H Conway was an investigator. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript.

Authors’ contributions

All authors participated in the development and review of the manuscript and approved the final version. The corresponding author had final responsibility to submit for publication. Drafts were developed by a professional publication writer according to the recommendations, documentation, and outline provided by the lead author.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Trademarks

Bexsero is a trademark of the GSK group of companies. Trumenba is a trademark of Pfizer Inc.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14760584.2023.2222015.

Additional information

Funding

GSK funded all costs associated with the development and the publishing of this manuscript. There were no personal payments to co-authors for their time or contribution.