The Committee was updated on clinical safety data from studies of a new meningococcal A conjugate vaccine (MenAfriVac, Serum Institute of India, Pune, India) and of plans for mass vaccination campaigns to be launched imminently. The vaccine is a lyophilized meningitis A conjugate vaccine developed by the Meningitis Vaccine Project. Safety data presented to the Committee in December 2009 did not raise any particular concerns, but the Committee highlighted the need for additional data from larger numbers of participants to better assess the safety profile.

The reactogenicity and safety of the vaccine have been evaluated in 7 clinical trials (3 of which are ongoing) in 5 countries (Gambia, Ghana, India, Mali and Senegal). These included one study of children aged 14 weeks to 18 months; the others have been conducted in volunteers aged 1–29 years, the target age group for the initial mass vaccination campaigns. As of 31 May 2010, a total of 4614 vaccinated participants and 2040 controls had been followed to collect data on immunogenicity and adverse events for at least 1 month after vaccination and for serious adverse events for at least 1 year. A total of 237 serious adverse events have been reported (including 16 deaths); after causality assessment, 235 of these events were considered to be unrelated to the vaccine. One of the serious adverse events that was considered to be probably vaccine-related was a hypersensitivity reaction with facial oedema in an infant aged 10 months; this is a well-documented hypersensitivity reaction occurring with meningococcal and other conjugate vaccines. The other vaccine-related serious adverse event was a case of simple febrile convulsion in a child aged 17 months following administration of the meningococcal A vaccine along with a pentavalent diphtheria–tetanus–pertussis plus Haemophilus infl uenzae type b plus hepatitis B vaccines. Both children recovered without sequelae. In all completed studies, the rates of other serious adverse events were similar in vaccinated and control participants. Most of the serious adverse events reported (189/237) accrued from an ongoing study of children aged 14 weeks–18 months; 74 (39%) of these were attributed to malaria, 66 (35%) to acute gastroenteritis, and 33 (14%) to acute respiratory tract infection. The occurrence of these events was consistent with the seasonal age-specific morbidity in the areas where the study is being conducted.

MenAfriVac has not been administered to pregnant or lactating women, but 15 women are known to have become pregnant shortly after administration. Of the 14 completed pregnancies studied, 13 resulted in a normal live-born infant and 1 in a stillbirth, which occurred 13 months after vaccination following obstructed labour in a 26-year-old woman with a history of stillbirth. The Committee recommended that studies be conducted to evaluate vaccine safety in pregnancy because of the likelihood of unintentional administration of the vaccine to pregnant women during mass vaccination campaigns.

The Committee also highlighted the importance of gaining additional information on MenAfriVac with respect to the duration of protection, its effect on carriage of Neisseria meningitidis, interactions with vaccines delivered by the Expanded Programme on Immunization, any possible effect on the prevalence of other serotypes (serotype replacement), and the safety and immunogenicity of the vaccine in groups considered to be potentially at high risk, such as people infected with HIV and those who are severely malnourished.

The Committee concluded that the data accumulated in clinical trials do not indicate that there are any significant safety issues with the vaccine. Since the vaccine will soon be used in mass campaigns, the Committee reiterated its previous advice that, where possible, phased introduction of the vaccine would be desirable so that additional safety data may be accumulated through careful postmarketing surveillance; the Committee was pleased to note that such studies are being planned.

Full report of GACVS meeting of 16-17 June 2010, published in the WHO Weekly Epidemiological Record on 23 July 2010

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.

Full report of GACVS meeting of 3-4 December 2009, published in the WHO Weekly Epidemiological Record on 29 January 2010