Genetic variation influences the B-cell response to immunization with a pneumococcal polysaccharide conjugate vaccine

Abstract

CBA/J mice immunized with pneumococcal 23F-CRM(197) vaccine produce significantly lower titers of 23F-specific antibodies and fewer 23F-specific antibody-secreting cells (ASC) than did BALB/c or (CBA/J x BALB/c)F(1) (CCBAF(1)) mice. The reduced 23F-specific titers of CBA/J versus BALB/c or CCBAF(1) mice are presumably related to lower frequencies of 23F-specific ASC influenced by genetic variation.

FIG. 1.

23F- and CRM₁₉₇-specific responses of BALB/c, CBA/J, and CCBAF₁ mice after two immunizations with 23F-CRM₁₉₇. (A) Total 23F-specific serum immunoglobulin κ chain titers (micrograms per milliliter) detected by PnPS solid-phase ELISA. (B) Frequency of 23F-specific κ ASC determined by PnPS solid-phase ELISpot assay. The data shown are a compilation of two experiments with the mean ± the standard error of the mean of a total of 24 mice per group. *, P < 0.004. (C)Total CRM₁₉₇-specific serum immunoglobulin κ chain titers (micrograms per milliliter) detected by CRM₁₉₇ solid-phase ELISA. (D) Frequency of CRM₁₉₇-specific κ ASC determined by PnPS solid-phase ELISpot assay. The data shown are a compilation of two experiments with the mean ± the standard error of the mean of a total of 24 mice per group. *, P < 0.003 for comparisons of selected groups with CCBAF₁.

FIG. 2.

19F- and CRM₁₉₇-specific responses of BALB/c, CBA/J, and CCBAF₁ mice after two immunizations with 19F-CRM₁₉₇. (A) Total 19F-specific serum immunoglobulin κ chain titers (micrograms per milliliter) detected by PnPS solid-phase ELISA. (B) Frequency of 19F-specific κ ASC determined by PnPS solid-phase ELISpot assay. The data shown are a compilation of two experiments with the mean ± the standard error of the mean of a total of 16 mice per group. (C) Total CRM₁₉₇-specific serum immunoglobulin κ chain titers (micrograms per milliliter) detected by CRM₁₉₇ solid-phase ELISA. (D) Frequency of CRM₁₉₇-specific κ ASC determined by CRM₁₉₇ solid-phase ELISpot assay. The data shown are a compilation of two experiments with the mean ± the standard error of the mean of a total of 16 mice per group.

FIG. 3.

PS- and CRM₁₉₇- specific antibody titers (micrograms per milliliter) of CBA/J mice primed with either 19F-CRM₁₉₇ or 23F-CRM₁₉₇ and boosted with either conjugate. Total serum immunoglobulin κ chain titers (micrograms per milliliter) of 19F-specific (A), 23F-specific (B), and CRM₁₉₇-specific (C) antibodies in CBA/J mice detected by PnPS (A and B) and CRM₁₉₇ (C and D) solid-phase ELISAs. 19F-specific (A) and CRM₁₉₇-specific (D) IgG1 levels detected in the same sera are also shown. The mean titers (micrograms per milliliter) ± the standard error of the mean of groups of five mice are shown.