Implications of genetic traits on vaccine efficacy

Literature on genetic screening in the community suggests that people having specific genotypes may either get or protect from infection, for example, malaria, human papilloma virus, and haemophilic influenza, for which vaccines are either already developed or being targeted. In such a situation, the evaluation of the efficacy of vaccine in the community needs to be examined with caution. In this paper, I present a method for the estimation of vaccine efficacy (VE) in the presence of genetic traits/component (theta) and the sample size required to estimate the 95 per cent CI with a given relative width for the estimated vaccine efficacy. Considering true efficacy ranging from 40 to 80 per cent and the possible values of the genetic component (theta) ranging from 0 to 60 per cent, the VE was estimated. The 95 per cent confidence intervals (CI) for the estimated VE for relative widths (R) 1.0 and 0.1 were computed. The sample sizes required for each of the unvaccinated and vaccinated cohorts were computed for estimating the 95 per cent CI for given incidence rates in the unvaccinated (Iu) cohort. In the presence of genetic traits I found that the VE was consistently overestimated. There existed change in the location as well as the asymmetry of the 95 per cent CIs over the point estimate of VE. The sample size required for estimating 95 per cent CI of VE was substantially reduced, resulting in savings. The more the genetic component (theta) affecting disease in the community, the more the savings in sample size. I examined the above estimators for (i) VE, (ii) 95 per cent CI for VE and (iii) sample size required for estimating 95 per cent CI of VE using the real-life data from the Haemophilus influenzae type b vaccine trial conducted in Finland and the global genetic structure of encapsulated H. influenza. Because of escalated VE and large savings in sample size for estimating the 95 per cent CI for VE, I recommend that the design should consider the genetic component that causes/protects from infection/disease for the evaluation of efficacy of vaccine in the field.