Clinical Immunology

Antigen-Specific Memory T Cell Responses after Vaccination with an Oral Killed Cholera Vaccine in Bangladeshi Children and Comparison to Responses in Patients with Naturally Acquired Cholera

Mohammad Arifuzzaman, Rasheduzzaman Rashu, Daniel T. Leung, M. Ismail Hosen, Taufiqur Rahman Bhuiyan, M. Saruar Bhuiyan, Mohammad Arif Rahman, Farhana Khanam, Amit Saha, Richelle C. Charles, Regina C. LaRocque, Ana A. Weil, John D. Clements, Randall K. Holmes, Stephen B. Calderwood, Jason B. Harris, Edward T. Ryan, Firdausi Qadri
DOI: 10.1128/CVI.00196-12

Article Figures & Data

Figures

  • Fig 1
    Fig 1

    Time line for vaccination, blood draws, and immunological assays. For vaccinees, d21 and d42 indicate 7 days and 4 weeks from the second dose of vaccine, respectively. For patients, d2 indicates the acute stage of infection; d7 and d30 indicate the early and late convalescent phases, respectively. (d, day; MBC, memory B cell).

  • Fig 2
    Fig 2

    Comparison of different toxin derivatives as T cell stimulatory antigens. Stimulation indices of patients (n = 9) at different time points are shown, with horizontal bars representing median stimulation indices. The toxin antigens include the following: recombinant cholera toxin B subunit (rCTB) (a gift from AM Svennerholm), the G33D variant of CTB (mCTB) (48), native CT, G33D variant of CT holotoxin (mCT) (48), double mutant LT (dmLT) (30), and membrane preparation of V. cholerae O1 (MP).

  • Fig 3
    Fig 3

    Comparison of different toxin derivatives as T cell stimulatory antigens in younger children receiving vaccine (n = 20), older children receiving vaccine (n = 20), and patients with naturally acquired cholera (n = 8). Mean stimulation indexes of T effector memory cells and their subtypes, with error bars representing standard errors of the means, are given. An asterisk (*) denotes a significant difference (P ≤ 0.05) from the baseline (day 2 for patients and day 0 for vaccinees). “∧” indicates a significant increase (P ≤ 0.05) in responses on day 7 for patients compared to day 21 responses in older vaccinees. The G33D variant of CT holotoxin (mCT), membrane preparation of V. cholerae O1 (MP), T effector memory cells (TEM), and T follicular helper cells (TFH) are analyzed.

  • Fig 4
    Fig 4

    Correlation between cholera toxin-specific early T cell responses and later B cell memory responses. Percentages of rCTB-specific IgG memory B cells in older vaccinees (n = 9) on day 42 correlated with stimulation indices of G33D variant of CT holotoxin (mCT) specific T effector memory (TEM) cells on day 21.

  • Fig 5
    Fig 5

    Cytokines in cell culture supernatants of older (n = 20) and younger (n = 20) children receiving vaccine and patients (n = 6) stimulated with mCT. Cytokine concentrations at different time points are shown for each vaccinee and patient, with horizontal bars representing medians. A single asterisk (*) indicates P ≤ 0.05, and double asterisks (**) indicate P ≤ 0.01 for later time points compared to earlier time points. Cytokines were measured 7 days after the second dose of vaccine on day 14 (i.e., on day 21) or 7 days after presenting for care for naturally acquired cholera (day 7).

Additional Files

  • Supplemental material

    Files in this Data Supplement:

    • Supplemental file 1 -

      Fig. S1. Dead cells after 6 days of ex vivo whole blood stimulation. Fig. S2a. Analysis of cells from a lymphoblast population with (A) or without (B) doublets. Fig. S2b. Gating strategy.

      PDF, 201K
Back to top
Download PDF
Citation Tools
Print

Email

Related Articles

Cited By...