Defining efficacy in meningococcal vaccine trials

Author(s): Paul B Keiser, Christopher J Gill

The incidence of meningococcal carriage and disease is, or will soon be, declining in many countries as the result of effective vaccination campaigns. The low incidence of disease requires the use of surrogate markers of protection in clinical trials of meningococcal vaccines. Assays of serum bactericidal activity (SBA) remain the primary efficacy outcome. Evidence that SBA assays are predictive of immune protection in an individual derives from prospectively studied epidemics; evidence that SBA assays are predictive of protection at the population level come from vaccine efficacy studies. Other immune mechanisms also play important roles, particularly in the large and possibly increasing proportion of meningococcal cases occurring in individuals with complement deficiencies. The declining incidence of asymptomatic carriage will result in less natural boosting of meningococcal immunity with a resulting shorter duration of protection. Our changing epidemiologic circumstances should prompt an ongoing re-assessment of our approach to evaluating vaccine efficacy.