Antibody avidity in humoral immune responses in Bangladeshi children and adults following administration of an oral killed cholera vaccine

Abstract

Antibody avidity for antigens following disease or vaccination increases with affinity maturation and somatic hypermutation. In this study, we followed children and adults in Bangladesh for 1 year following oral cholera vaccination and measured the avidity of antibodies to the T cell-dependent antigen cholera toxin B subunit (CTB) and the T cell-independent antigen lipopolysaccharide (LPS) in comparison with responses in other immunological measurements. Children produced CTB-specific IgG and IgA antibodies of high avidity following vaccination, which persisted for several months; the magnitudes of responses were comparable to those seen in adult vaccinees. The avidity of LPS-specific IgG and IgA antibodies in vaccinees increased significantly shortly after the second dose of vaccine but waned rapidly to baseline levels thereafter. CTB-specific memory B cells were present for only a short time following vaccination, and we did not find significant memory B cell responses to LPS in any age group. For older children, there was a significant correlation between CTB-specific memory T cell responses after the second dose of vaccine and CTB-specific IgG antibody avidity indices over the subsequent year. These findings suggest that vaccination induces a longer-lasting increase in the avidity of antibodies to a T cell-dependent antigen than is measured by a memory B cell response to that antigen and that early memory T cell responses correlate well with the subsequent development of higher-avidity antibodies.

Fig 1

Schedules for vaccination, blood collection, and immunological response measurements for children and adult vaccinees. For child (younger and older) vaccinees, day 21 and day 42 indicate 7 and 28 days, respectively, after the second dose of vaccine at day 14. For adults, day 17 and day 42 indicate 3 and 28 days, respectively, after the second dose of vaccine. ●, vaccination; ○, study follow-up assessments.

Fig 2

Vibriocidal antibody responses in different age groups after administration of two doses of oral cholera vaccine, with a 2-week interval (day 0 and day 14). Bars, mean responses; error bars, standard errors of the mean. ∗, statistically significant differences (P < 0.05) from the baseline (day 0) titer.

Fig 3

Plasma CTB-specific (A and B) and LPS-specific (C and D) antibody responses in Bangladeshi vaccine recipients of different age groups who received two doses of oral cholera vaccine, with an interval of 2 weeks (day 0 and day 14). (A and C) IgG responses. (B and D) IgA responses. Bars, mean responses; error bars, standard errors of the mean. ∗, statistically significant differences (P < 0.05) from baseline (day 0); #, statistically significant differences between age groups (P < 0.05).

Fig 4

Avidity index (AI) values for CTB-specific (A and B) and LPS-specific (C and D) antibodies in Bangladeshi vaccine recipients of different age groups who received two doses of oral cholera vaccine, with an interval of 2 weeks (day 0 and day 14). (A and C) IgG responses. (B and D) IgA responses. Bars, mean responses; error bars, standard errors of the mean. ∗, statistically significant differences (P < 0.05) from baseline (day 0) AI; #, statistically significant differences between age groups (P < 0.05).

Fig 5

CTB-specific (A and B) and LPS-specific (C and D) memory B cell responses in Bangladeshi vaccine recipients who received two doses of oral cholera vaccine, separated by 2 weeks (day 0 and day 14). (A and C) IgG responses. (B and D) IgA responses. Memory B cell responses are expressed as percent antigen-specific responses of total isotype-specific memory B cells. Bars, mean responses; error bars, standard errors of the mean. ∗, statistically significant differences (P < 0.05) from baseline (day 0).