Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge

Abstract

Inactivated poliovirus vaccine (IPV) may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV) after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24)). In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11]) or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]). There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

Figure 1. Flow diagram showing included studies according to PRISMA guidelines .

The number of published articles identified by the given search term for initial screening and the resulting studies identified and included in the systematic review and meta-analysis are shown.

Figure 2. Relative odds of shedding vaccine poliovirus after challenge among individuals vaccinated with OPV compared with unvaccinated individuals.

Odds ratios (ORs) and 95% confidence intervals for individual studies are indicated by the boxes and grey lines. The summary odds ratio for each serotype is given by a diamond with the 95% confidence interval (CI) indicated by its width. The χ² test for heterogeneity among studies was significant for serotypes 2 and 3 (p-values 0.33, <0.001, and 0.001 for serotypes 1, 2, and 3, respectively) and for the overall odds ratio (p-value<0.001). Details of the studies included are given in Table S1. *Ghendon et al. 1961 compare vaccinated and unvaccinated children who were confirmed seropositive and seronegative, respectively.

Figure 3. Relative odds of shedding vaccine poliovirus after challenge among individuals vaccinated with IPV compared with unvaccinated individuals.

Labeling as for Figure 2. The χ² test for heterogeneity among studies was not significant for any serotype (p-values 0.11, 0.47, and 0.07) or for the overall odds ratio (p-value 0.10). *Ghendon et al. 1961 compare vaccinated and unvaccinated children who were confirmed seropositive and seronegative, respectively.

Figure 4. Relative odds of shedding vaccine poliovirus after challenge among individuals vaccinated with OPV compared with IPV.

Labeling as for Figure 2. The χ² test for heterogeneity among studies was significant for serotypes 1 and 3 (p-values<0.001, 0.79, and 0.01 for serotypes 1, 2, and 3, respectively) and for the overall odds ratio (p-value<0.001). *Ghendon et al. 1961 compare vaccinated and unvaccinated children who were confirmed seropositive and seronegative, respectively.

Figure 5. Relative odds of shedding vaccine poliovirus after challenge among individuals vaccinated with IPV in addition to OPV compared with individuals vaccinated with OPV only.

Labeling as for Figure 2. The schedule indicates the number and type of OPV doses received by both groups and the number of doses of IPV that were added in the intervention group. In two studies, IPV was administered simultaneously with OPV at 6, 10, and 14 weeks (Modlin et al. 1997 and du Chatelet et al. 2003 [48]), and in one study IPV was administered before and at the same time as OPV (schedule was IPV, IPV/OPV, OPV, OPV at 2, 4, 6, 15 months; WHO Collaborative Study Group on Oral and Inactivated Poliovirus Vaccines 1997 [49]). The χ² test for heterogeneity among studies for serotypes 1 and 3 was not significant for each serotype (p-values 0.13 and 0.08) or for the serotypes combined (p-value 0.14).