Immunogenicity and effectiveness of routine immunization with 1 or 2 doses of inactivated poliovirus vaccine: systematic review and meta-analysis

Abstract

Background: The World Health Organization has recommended that all 124 countries currently using only oral poliovirus vaccine (OPV) introduce at least 1 dose of inactivated poliovirus vaccine (IPV) before the global withdrawal of serotype 2 OPV in 2016. A 1- or 2-dose schedule, potentially administered intradermally with reduced antigen content, may make this affordable.

Methods: A systematic review and meta-analysis of studies documenting seroconversion after 1 or 2, full or fractional (1/5) doses of enhanced-potency IPV was performed. Studies reporting the clinical efficacy of IPV were also reviewed.

Results: Twenty study arms from 12 published articles were included in the analysis of seroconversion. One full dose of intramuscular IPV seroconverted 33%, 41%, and 47% of infants against serotypes 1, 2, and 3 on average, whereas 2 full doses seroconverted 79%, 80%, and 90%, respectively. Seroconversion increased with age at administration. Limited data from case-control studies indicate clinical efficacy equivalent to the proportion seroconverting. One fractional dose of intradermal IPV gave lower seroconversion (10%-40%), but after 2 doses seroconversion was comparable to that with full-dose IPV.

Conclusions: Routine immunization with 2 full or fractional doses of IPV given after 10 weeks of age is likely to protect >80% of recipients against poliomyelitis if poliovirus reemerges after withdrawal of OPV serotypes.

Keywords: IPV; antibody; efficacy; endgame; eradication; immunogenicity; inactivated poliovirus vaccine; poliomyelitis; seroconversion.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Figures

Figure 1.

Proportion of children seroconverting to each serotype after 1 dose of inactivated poliovirus vaccine (IPV), plotted against age at administration. A, Full-potency IPV given intramuscularly. B, Fractional (1/5) dose IPV given intradermally using a needle-free device. The dashed line shows the maximum-likelihood linear trend (likelihood ratio test for trend P <.001, <.001, and .49 for serotypes 1, 2, and 3 in A, and P <.001, <.001, and .027, respectively, in B). The error bars show the 95% confidence intervals for the data. Seroconversion was defined in each study as either a 4-fold rise in neutralizing antibody titer compared with that expected based on the expected decline in maternal antibodies, or detection of neutralizing antibodies in children previously seronegative (see Supplementary Table 1 for details for each study). Seroconversion data from a study of IPV given at birth in India is shown with a gray fill for serotypes 1 and 2 (A), as a high proportion of infants showed seroconversion to these serotypes in the control arm of the study where IPV was not administered at birth [8]. Data from this study for serotypes 1 and 2 were therefore not included when estimating the best-fit linear trend.

Figure 2.

Proportion of children seroconverting to each serotype after 2 doses of inactivated poliovirus vaccine (IPV), plotted against age at administration of the first dose. A, Full-potency IPV given intramuscularly. B, Fractional (1/5) dose IPV given intradermally using a needle and syringe or needle-free device. The legend indicates the interval between the doses, and the error bars the 95% confidence intervals. The dashed line indicates the trend in seroconversion with age at administration of the first dose based on an exponential curve with intercept and asymptote estimated from the data using maximum likelihood. The asymptote was constrained to be ≤100%. Seroconversion is defined as in Figure 1 (see Supplementary Table 2 for details for each study). Data from the study in India with significant seroconversion to serotypes 1 and 2 in the control arm are shown in gray as for Figure 1 and excluded from the maximum likelihood curve fit [8].