Intestinal Immunity to Poliovirus Following Sequential Trivalent Inactivated Polio Vaccine/Bivalent Oral Polio Vaccine and Trivalent Inactivated Polio Vaccine–only Immunization Schedules: Analysis of an Open-label, Randomized, Controlled Trial in Chilean Infants

Figure 1.. Flow diagram for the selection of the analytical cohort from NCT 01841671, an investigation of the “Immunogenicity of 1 or 2 Doses of bOPV in Chilean Infants Primed with IPV Vaccine (IPV002ABMG),” undertaken in Santiago, Chile, between 25 April and 1 August 2013. Abbreviations: bOPV, bivalent oral polio vaccine; IgA, immunoglobulin A; IPV, trivalent inactivated polio vaccine; neut., neutralization. aReasons for exclusion are not mutually exclusive. bSubjects with missing type 2 oral poliovirus vaccine shedding data from at least 1 visit at 28, 29, 30, 31, or 32 weeks of age. cSubjects with missing polio type 2–specific stool neutralization and immunoglobulin A data from at least 1 visit at 28 or 30 weeks of age. dPolio type 1–specific immunoglobulin A data were missing from the visit at 30 weeks of age in 2 of the included subjects in the IPV-IPV-bOPV group and 1 in the IPV-IPV-IPV group. eType 1– and 2–specific serum neutralization data were missing from the visits at 28 and/or 29 weeks of age in 1 of the included subjects in the IPV-IPV-bOPV group and 3 in the IPV-bOPV-bOPV group.

Figure 2.. Systemic and intestinal immunity to polio types 1 and 2 at the time of the monovalent oral polio vaccine type 2 challenge (28 weeks of age) in infants previously immunized with IPV-bOPV-bOPV (n = 48), IPV-IPV-bOPV (n = 54), and IPV-IPV-IPV (n = 50). (A) Serum neutralization specific to poliovirus types 1 (P = .0001) and 2 (P = .0001), (B) stool neutralization specific to poliovirus types 1 (P = .0001) and 2 (P = .06), and (C) stool immunoglobulin A specific to poliovirus types 1 (P = .0001) and 2 (P = .004). Overall P values are from Kruskal-Wallis tests comparing the distributions of immune markers by primary vaccine group assignment; pairwise P values are from post hoc Dunn’s tests with Bonferroni correction for multiple testing within each grouping. Horizontal black bars indicate the median levels. Abbreviations: bOPV, bivalent oral polio vaccine; IgA, immunoglobulin A; IPV, trivalent inactivated polio vaccine; mOPV2, monovalent oral polio vaccine type 2.

Figure 3.. Polio type 2–specific intestinal immune responses to mOPV2 challenge in a random subgroup of infants (n = 20). (A) mOPV2 shedding, (B) type 2–specific stool neutralization, and (C) type 2–specific stool immunoglobulin A. Blue, circle-shaped markers indicate infants immunized with IPV-bOPV-bOPV (n = 7); orange, triangle-shaped markers indicate infants immunized with IPV-IPV-bOPV (n = 7); and red, square-shaped markers indicate infants immunized with IPV-IPV-IPV (n = 6). Abbreviations: bOPV, bivalent oral polio vaccine; IgA, immunoglobulin A; IPV, trivalent inactivated polio vaccine; mOPV2, monovalent oral polio vaccine type 2.

Figure 4.. Pairwise correlations between type 2–specific stool neutralization, immunoglobulin A, and mOPV shedding 2 weeks after mOPV2 challenge (ie, 30 weeks of age). Abbreviations: bOPV, bivalent oral polio vaccine; IgA, immunoglobulin A; IPV, trivalent inactivated polio vaccine; mOPV2, monovalent oral polio vaccine type 2.

Figure 5.. Intestinal immunity to polio type 2 at the time of and 2 weeks after monovalent oral polio vaccine type 2 challenge (ie, 28 and 30 weeks of age) by reported duration of breastfeeding. P values are from Mann-Whitney U tests comparing the distributions of immune markers by breastfeeding category. Horizontal black bars indicate the median levels. Blue, circle-shaped markers indicate infants immunized with IPV-bOPV-bOPV (n = 48); orange, triangle-shaped markers indicate infants immunized with IPV-IPV-bOPV (n = 54); and red, square-shaped markers indicate infants immunized with IPV-IPV-IPV (n = 50). Abbreviations: bOPV, bivalent oral polio vaccine; IgA, immunoglobulin A; IPV, trivalent inactivated polio vaccine; mOPV2, monovalent oral polio vaccine type 2.