Review of safety profile on meningococcal A conjugate vaccine from clinical trials
The Committee was given an overview of the MenAfriVacTM vaccine clinical safety data and risk management plan. This is a lyophilized meningitis A conjugate vaccine developed by the Meningitis Vaccine Project. Each dose of 0.5ml vaccine contains: PsA10 µg, TT conjugate 10–33 µg, aluminium phosphate adjuvant 0.3mg Al3+ and thiomersal 0.01%. Four clinical trials have evaluated the reactogenicity and safety of MenAfriVacTM , and 2 additional trials are ongoing. The phase I study was conducted in 18–34 year-old volunteers in India; Phase II and II/III studies, to assess the safety and immunogenicity of the vaccine, were performed in 1–29 year-old people in Africa and India. To date, a total of 1126 subjects have been followed to evaluate the safety and immunogenicity of the MenAfriVacTM vaccine.
The subjects in the trials were followed for AEFI for at least 1 month after vaccination and for serious adverse events up to at least 1 year after vaccination. MenAfriVacTM vaccine did not cause any adverse reactions beyond 4 days post immunization; the adverse events observed were comparable between study and control vaccine groups, except for injection site tenderness which was more common (13%) among those in the MenAfriVacTM vaccine group. No particular safety concerns were identified in any of the age groups evaluated. None of the 137 serious adverse events (including 14 deaths) reported in the vaccine studies were assessed to be related to the study vaccines.
The Committee highlighted issues yet to be addressed with respect to use of the vaccine. These included the need for booster doses, their effect on carriage, interactions with EPI if given to infants and the possibility of serotype replacement. There are no data on the effects of the vaccine in special groups such as those HIV-infected and those severely malnourished.
The Committee also reviewed the safety profile of other meningococcal conjugate vaccines. Pre- and post-licensure data for meningococcal conjugate vaccines have not shown marked differences between the vaccines, and reported serious adverse events are rare. Based on potential safety signals that were identified with other meningococcal conjugate vaccines, the pharmacovigilance for the meningococcal A conjugate vaccine should pay specific attention to anaphylactic reactions, severe cutaneous reactions, nephrotic syndrome, meningitis-like symptoms, myocarditis and Guillain–Barré syndrome. These other vaccines differed from MenAfriVacTM with respect to the excipients in the vaccine, particularly aluminium phosphate and thiomersal. Establishment of proactive pharmacovigilance, with a risk management programme that includes safety evaluation during a phased roll-out, should therefore be an essential component of introduction plans for this new vaccine.
The Committee concluded that available data for MenAfriVacTM vaccine do not indicate any special cause for concern. However, further studies, particularly post-marketing surveillance, are needed to better assess the safety profile of the vaccine.