Safety Monitoring in Group A Meningococcal Conjugate Vaccine Trials: Description, Challenges, and Lessons

Determination of the safety profile of any vaccine or drug is crucial before its routine utilization in the community, as drugs that show a safe profile in animal studies can show a different effect in humans [1]. Appropriate study designs and study sizes are needed to determine both short- and long-term safety [2]. In the 1990s, the use of high-dose measles vaccine was associated with increased mortality in females, a finding that led the World Health Organization (WHO) to rescind its earlier recommendation on the vaccine [3, 4]. Although scientists scrambled to explain the reason for such an unusual finding, it further emphasized the need for due diligence in assessing the safety of any vaccine before it can be introduced into the population [3, 5]. There was a similar occurrence with the first oral rotavirus vaccine [6]. Following the introduction of Haemophilus influenzae type b (Hib) conjugate, there were reports of occurrence of Guillain-Barre syndrome (GBS) [7, 8]. In a rather more dramatic fashion, rare cases of GBS were also reported in the United States in a temporal relationship following administration of Menactra [9]. Although several hypotheses have been propounded to explain the possible occurrence of GBS following immunization [8, 10], comparison with expected rates of GBS has been inconclusive to define if there is increased risk of GBS with the administration of diphtheria, tetanus, polio, Hib combination vaccine, and quadrivalent meningococcal conjugate vaccine [10, 11]. Taken together, these findings highlight the need for due rigor in establishment of the safety profile of any vaccine. Thus, the trials for PsA-TT (MenAfriVac) were designed to ensure that both common and rare adverse events (AEs) were detectable throughout the clinical development period.