# Safety Profile of the 4CMenB (Bexsero®) Vaccine: A Systematic Review and Meta-Analysis of Adverse Events in Clinical Trials

## TL;DR

This study reviews and analyzes the safety of the Bexsero® vaccine, finding that it has a favorable safety profile with mostly mild and temporary side effects.

## Contribution

A systematic review and meta-analysis of adverse events associated with the 4CMenB (Bexsero®) vaccine in clinical trials.

## Key findings

- Local pain was the most common adverse event, occurring in up to 94% of cases.
- Systemic events like irritability, fatigue, and fever were reported but were generally mild and self-limiting.
- The vaccine's safety profile supports its inclusion in routine childhood immunization programs.

## Abstract

Background: The 4CMenB vaccine (Bexsero®) contains surface proteins from Neisseria meningitidis serogroup B and is recommended from 2 months of age. The most frequently reported adverse events are fever, injection site pain, and fatigue. Thus, this study aimed to estimate the incidence of local and systemic adverse events associated with the administration of the 4CMenB (Bexsero®) vaccine. Methods: A systematic review and meta-analysis of clinical trials published up to 28 February 2025 were conducted using PubMed, ScienceDirect, and Web of Science. Human studies available in English, Spanish, French, German, or Italian were exclusively included. Adverse events following the first dose of the vaccine were analyzed. Pooled proportions with 95% confidence intervals were calculated, and heterogeneity across studies was assessed using the I2 statistics. Results: Ten clinical trials comprising 13,345 participants were included. The most common adverse event was local pain (occurring in up to 94% of cases), followed by induration, erythema, and edema, with frequencies ranging from 25% to 45%. The most frequently reported systemic events were irritability (up to 75%), fatigue (51–59%), fever (up to 60%), headache (42–49%), and persistent crying (50–65%). Most adverse events were mild and self-limiting. Conclusions: The 4CMenB (Bexsero) vaccine exhibits a favorable safety profile, characterized by a predominance of mild and transient local adverse events. Although several systemic events were reported, their overall frequency was generally low. These findings support the continued inclusion of Bexsero® in routine childhood immunization programs.