Menfive® (Menengococcal Conjugate) Vaccine Safety
The virtual meeting of the Global Advisory Committee on Vaccine Safety (GACVS) reviewed the safety data collected during the first use of MenFive®, a Neisseria meningitidis Conjugate vaccine (A, C, W, X, Y). Experts from the GACVS reviewed safety data from the use of MenFive® in outbreak response campaigns in Niger and Nigeria in 2024. The campaigns implemented a three-pronged vaccine safety surveillance system, including strengthened routine pharmacovigilance, cohort event monitoring (CEM), and sentinel surveillance in hospitals.
The CEM protocol involved collecting data on local and systemic reactions, hospital visits, and medical records. The CEM in Niger and Nigeria enrolled in total 48,889 participants, with 37,519 (77%) being followed up till day 7 and 31,961 (65%) till day 28. The most common solicited reactions at the injection site were pain, erythema, swelling, itching, induration, warmth, and bruise. Systemic reactions included pyrexia, abdominal pain, hemorrhage, myalgia, headache, vomiting, diarrhea, arthralgia, hypersensitivity, nausea, fatigue, hypertension, and hypotension. The GACVS members discussed the follow-up methods, staff training, and the comparability of reactogenicity rates with pre-approval data. They also highlighted the importance of considering the context of a reactive campaign and the potential for individuals to be vaccinated while in the incubation period of meningococcal infection.
The results from a systematic review of hospital registers were not presented. A clinical case of a 17-year-old female from Nigeria, who developed meningococcal disease after vaccination was presented. This started with fever, headache, skin rash, cellulitis and gangrene in multiple limbs, beginning one day after vaccination. Cerebrospinal fluid examination showed presence of N. meningitis type C nucleic acid, leading to a diagnosis of meningococcaemia. Importantly, the vaccine had been administered in the setting of an ongoing outbreak. The national committee for causality assessment reviewed the case and classified the event as inconsistent with the vaccine or vaccination.
The overall results indicated that the MenFive® vaccine is safe and effective, with most local and systemic reactions being mild to moderate. There was a discussion about the high rate of injection site pain, with suggestions that it could be related to vaccine formulation or administration technique. Serious adverse events were rare, and no formal safety signals were identified. However, some areas require further analysis, including injection site pain and hemorrhages.
The GACVS made several recommendations to enhance the safety monitoring of the MenFive® vaccine during future deployments: (1) Injection Site Symptoms: Report the frequency of injection site pain and other symptoms observed in CEM and compare them with data from randomized controlled trials. An age-based analysis was also suggested to identify potential trends. (2) Hemorrhage Cases: Conduct further case-based reviews to better understand the clinical presentation of hemorrhage cases. (3) Serious Adverse Events: Document serious adverse events where applicable. (4) Enhanced Safety Monitoring: Strengthen safety monitoring and response mechanisms during the upcoming deployment of MenFive® in other regions. This includes developing standard protocols and templates for CEM, sharing lessons learned from CEM and hospital-based surveillance, tailoring adverse event following immunization (AEFI)/adverse event of special interest (AESI) surveillance to outbreak contexts, and strengthening data interpretation and communication strategies to avoid misattribution of events.
The GACVS emphasized the importance of clear communication about the potential risk of developing the primary illness before the protective immune response is established, especially when the vaccine is provided as an outbreak response.