Immune Priming and Long-term Persistence of Memory B Cells After Inactivated Poliovirus Vaccine in Macaque Models: Support for at least 2 Doses

Figures

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  Figure 1.. Overall experimental design. Abbreviations: Abs, antibodies; i.d., intradermal; i.m., intramuscular; IPV, inactivated poliovirus vaccine.

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  Figure 2.. Longitudinal analysis of humoral immunity following a single intramuscular full-dose inactivated poliovirus vaccine (IPV) immunization. Neutralization titers (A), immunoglobulin (Ig) M antibody (Ab) binding titers (B), and IgG Ab binding titers (C) specific to each of the poliovirus serotypes were measured. The macaques were divided into 2 categories: neutralizing (NT) (Ab) inducing (NT Ab+) and NT Ab noninducing (NT Ab−) based on detectable NT Ab titers within the first 30 days post single IPV dose immunization. The dashed lines indicate data for individual macaques, and the solid line indicates the geometric mean of the titers of individual macaques at the particular time post-vaccination. Of the 16 macaques immunized with single intramuscular full-dose IPV, all 16 were analyzed at days 0, 5, 7, 14, 21, 30, 90, and 150; 8 were analyzed at days 210, 270, and 300; and 4 were analyzed at day 480. Dotted red lines indicate limit of detection. Abbreviations: Ig, immunoglobulin; NT Abs, neutralizing antibody.

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  Figure 3.. Longitudinal analysis of humoral immunity following a single intradermal fractional-dose inactivated poliovirus vaccine (IPV) immunization. Neutralization titers (A), immunoglobulin (Ig) M antibody (Ab) binding titers (B), and (C) IgG Ab binding titers (C) specific to each of the poliovirus serotypes were measured. The macaques were divided into 2 categories: neutralizing (NT) Ab) inducing (NT Ab+) and NT Ab noninducing (NT Ab−) based on detectable NT Ab titers within the first 30 days post single IPV dose immunization. The dashed lines indicate data for individual macaques, and the solid line indicates the geometric mean of the titers of individual macaques at the particular time post-vaccination. Of the 16 macaques immunized with single intradermal fractional-dose IPV, all 16 were analyzed at days 0, 5, 7, 14, 21, 30, 90, and 150; 8 were analyzed at days 210, 270, and 300; and 4 were analyzed at day 480. Dotted red lines indicate limit of detection. Abbreviations: Ig, immunoglobulin; NT Abs, neutralizing antibody.

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  Figure 4.. Memory B cell (MBC) induction and persistence following a single inactivated poliovirus vaccine (IPV) immunization. Example of MBC enzyme-linked immunospot assay (A), frequencies of MBCs specific to each of the poliovirus serotypes in unimmunized vs day 30 post single full-dose IPV intramuscular (i.m.) immunized macaques (B), longitudinal analysis of blood-circulating MBCs in single full-dose IPV i.m. immunized macaques (C), and longitudinal analysis of blood-circulating MBCs in single fractional-dose IPV intradermal immunized macaques (D) are shown. In panels C and D, macaques were divided into 2 categories: neutralizing antibody (NT Ab) inducing (NT Ab+) or NT Ab noninducing (NT Ab−) based on detectable NT Ab titers within the first 30 days post single IPV dose immunization. The dashed lines indicate data for individual macaques, and the solid line indicates the geometric mean of the MBC frequencies of individual macaques at the particular time post-vaccination. Of the 16 macaques immunized in each of the full or fractional groups, all 16 were analyzed at days 0, 30, 90, and 150; 8 were analyzed at days 210, 270, and 300; and 4 were analyzed at day 480. Dotted red lines…

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  Figure 5.. Assessment of long-term memory with 2-dose inactivated poliovirus vaccine (IPV). (A) Two-dose full (intramuscular) IPV. (B) Two-dose fractional (intradermal) IPV. Neutralizing antibody titers (left panels), immunoglobulin G titers (middle panel), and memory B cell frequencies (right panel) specific to each of the poliovirus serotypes are shown. Second dose of IPV was given 5 months post first dose. Blue lines indicate individual macaques that generated neutralization titers after the first dose of IPV, and the red lines indicate individual macaques that failed to generate neutralization titers after the first dose of IPV. Unjointed dots in the right-most panel at day 150 + 480 indicate the frequencies of draining lymph node memory B cells specific to each of the poliovirus serotypes. Abbreviations: Ig, immunoglobulin; IPV, inactivated poliovirus vaccine.

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  Figure 6.. Enumeration of antibody-secreting plasma cells (ASCs) in single vs 2-dose inactivated poliovirus vaccine (IPV) immunization. (A) Full-dose IPV intramuscular immunized macaques. (B) Fractional-dose IPV intradermal immunized macaques. ASCs were enumerated as percent of total immunoglobulin G–secreting cells in blood or bone marrow against poliovirus type 1, type 2, and type 3 specificities. Abbreviations: ASC, antibody-secreting plasma cell; Ig, immunoglobulin; IPV, inactivated poliovirus vaccine.

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  Figure 7.. Analysis of long-term persistence of immune priming to each of the poliovirus serotypes long-term post a single full-dose inactivated poliovirus vaccine (IPV) intramuscular ( i.m.). (A) IPV challenge was done in 4 macaques 300 days after single full-dose IPV (i.m.). (B) IPV challenge was done in 4 macaques 480 days after single full-dose IPV (i.m.). Neutralizing antibody (NT Ab) titers (left panel), immunoglobulin (Ig) G titers (middle panel), and memory B cell frequencies (right panel) are shown for individual macaques. Blue lines indicate those macaques that generated NT Abs after the single IPV immunization. Red lines indicate those macaques that failed to generate neutralization titers after the single IPV immunization. The center panel shows the plasma IgG-binding Ab titers measured in these individual macaques for all 3 poliovirus vaccine antigens; data are represented as the endpoint titer. Abbreviations: Ig, immunoglobulin; IPV, inactivated poliovirus vaccine.

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  Figure 8.. Analysis of long-term persistence of immune priming to each of the poliovirus serotypes long-term post a single fractional-dose inactivated poliovirus vaccine (IPV) intradermal (i.d.). (A) IPV challenge was done in 4 macaques 300 days after single fractional-dose IPV (i.d.). (B) IPV challenge was done in 4 macaques 480 days after fractional-dose IPV (i.d.). Neutralizing antibody (NT Ab) titers (left panel), immunoglobulin (Ig) G titers (middle panel), and memory B cell frequencies (right panel) are shown for individual macaques. Blue lines indicate those macaques that generated NT Abs after the single IPV immunization. Red lines indicate those macaques that failed to generate neutralization titers after the single IPV immunization. The center panel shows the plasma IgG-binding Ab titers measured in these individual macaques for all 3 poliovirus vaccine antigens; data are represented as the en-point titer. Abbreviations: Ig, immunoglobulin; IPV, inactivated poliovirus vaccine.