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Review
. 2024 Dec 31;20(1):2357924.
doi: 10.1080/21645515.2024.2357924. Epub 2024 Jul 8.

4CMenB journey to the 10-year anniversary and beyond

Véronique Abitbol  1 , Federico Martinón-Torres  2   3   4 , Muhamed-Kheir Taha  5 , Terry Nolan  6 , Alessandro Muzzi  7 , Stefania Bambini  7 , Ray Borrow  8 , Daniela Toneatto  7 , Laura Serino  7 , Rino Rappuoli  7 , Mariagrazia Pizza  7
Affiliations
Review

4CMenB journey to the 10-year anniversary and beyond

Véronique Abitbol et al. Hum Vaccin Immunother. .

Abstract

The 4-component meningococcal serogroup B (MenB) vaccine, 4CMenB, the first broadly protective, protein-based MenB vaccine to be licensed, is now registered in more than 50 countries worldwide. Real-world evidence (RWE) from the last decade confirms its effectiveness and impact, with infant immunization programs showing vaccine effectiveness of 71-95% against invasive MenB disease and cross-protection against non-B serogroups, including a 69% decrease in serogroup W cases in 4CMenB-eligible cohorts in England. RWE from different countries also demonstrates the potential for additional moderate protection against gonorrhea in adolescents. The real-world safety profile of 4CMenB is consistent with prelicensure reports. Use of the endogenous complement human serum bactericidal antibody (enc-hSBA) assay against 110 MenB strains may enable assessment of the immunological effectiveness of multicomponent MenB vaccines in clinical trial settings. Equitable access to 4CMenB vaccination is required to better protect all age groups, including older adults, and vulnerable groups through comprehensive immunization policies.

Keywords: 4CMenB; Bexsero; Neisseria gonorrhoeae; Neisseria meningitidis; cross-protection; effectiveness; impact; real-world evidence; safety; serogroup B.

Plain language summary

Invasive meningococcal disease, caused by the bacterium Neisseria meningitidis(meningococcus), is rare but often devastating and can be deadly. Effective vaccines are available, including vaccines against meningococcal serogroup B disease. In 2013, the 4-component meningococcal serogroup B vaccine, 4CMenB, became the first broadly protective, protein-based vaccine against serogroup B to be licensed, with the second (bivalent vaccine, MenB-FHbp) licensed the following year. 4CMenB is now registered in more than 50 countries, in the majority, for infants and all age groups. In the US, it is approved for individuals aged 10–25 years. Evidence from immunization programs in the last decade, comparing vaccinated and unvaccinated individuals and the same population before and after vaccination, confirms the effectiveness and positive impact of 4CMenB against serogroup B disease. This also demonstrates that 4CMenB can provide protection against invasive diseases caused by other meningococcal serogroups. Furthermore, N. meningitidis is closely related to the bacterium that causes gonorrhea, N. gonorrhoeae, and emerging real-world evidence suggests that 4CMenB provides additional moderate protection against gonococcal disease. The safety of 4CMenB when given to large numbers of infants, children, adolescents, and adults is consistent with the 4CMenB safety profile reported before licensure.For the future, it would be beneficial to address differences among national guidelines for the recommended administration of 4CMenB, particularly where there is supportive epidemiological evidence but no equitable access to vaccination. New assays for assessing the potential effectiveness of meningococcal serogroup B vaccines in clinical trials are also required because serogroup B strains circulating in the population are extremely diverse across different countries.

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Conflict of interest statement

VA, AM, DT, SB, and LS are employed by and hold financial equities in GSK.

RR and MP are former employees of GSK. MP is Professor at Imperial College.

FMT received honoraria from Sanofi, MSD, Moderna, GSK, Biofabri, AstraZeneca, Novavax, Janssen, and Pfizer. He also received financial support for travel and attending meetings from Pfizer, MSD, GSK, and Sanofi. He is a member of ETAGE – WHO Europe, coordinator of Spanish Pediatric Critical Trials Network, and coordinator of WHO collaborating center for vaccine safety of Santiago de Compostela. As Principal Investigator in randomized controlled trials of Ablynx, Abbot, Seqirus, Sanofi, MSD, Merck, Pfizer, Roche, Regeneron, Janssen, Medimmune, Novavax, Novartis, and GSK, he received financial support through his institution.

MKT declares that the Institut Pasteur received work contracts funded by GSK, Pfizer, and Sanofi. He also reports the patent NZ630133A “Vaccines for serogroup X meningococcus” issued with GSK.

TN declares that the University of Melbourne and Murdoch Children’s Research Institute received research grants for clinical trials from Iliad, Dynavax, Sanofi, Moderna, and CSL Seqirus. He also received personal payments for consultant fees from AstraZeneca, Pfizer, CSL Seqirus, and MSD; for participation on a Data Safety Monitoring Board or Advisory Board from Moderna, Clover, Novavax, Serum Institute of India, Technovalia, and Moderna; and support for attending meetings from MSD, GSK, and AstraZeneca. He also declares leadership or fiduciary role in another board, society, committee, or advocacy group for the mRNA Victoria Scientific Ad Board (unpaid), and for the Advances in mRNA Science Advisory Board (personal payment. Independent body but funded by an untied grant from Moderna).

RB performs contract research on behalf of UKHSA for GSK, Pfizer, and Sanofi Pasteur.

The authors declare no other financial and non-financial relationships and activities.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Road map leading to the regulatory approval and distribution of 4CMenB in more than 50 countries worldwide and to the inclusion of 4CMenB in national and regional immunization programs since initial registration.
Figure 2.
Figure 2.
Recommendations in 16 national immunization programs for the coadministration (co-adm) of routine childhood vaccines with 4CMenB and the use of prophylactic paracetamol (known as acetaminophen in the United States).,
Figure 3.
Figure 3.
Real-world evidence of the effectiveness, impact, and safety of 4CMenB.
Figure 4.
Figure 4.
Observed and projected serogroup B invasive disease cases in South Australia before (2003–2016) and after 4CMenB vaccination of students aged 16–19 years as part of the ‘B part of It’ program.
Figure 5.
Figure 5.
Ongoing and completed studies on the potential for 4CMenB to protect against Neisseria gonorrhoeae infection.
Figure 6.
Figure 6.
Potential coverage of 4CMenB against MenB strains circulating worldwide, as predicted by Meningococcal Antigen Typing System (MATS).
Figure 7.
Figure 7.
Characteristics of the traditional human serum bactericidal antibody (hSBA) assay and the endogenous complement hSBA (enc-hSBA) in relation to the assessment of meningococcal serogroup B (MenB) vaccines.,.
See this image and copyright information in PMC

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