Details of the Antibody Dynamics Models

Supplementary

Details of the antibody dynamics models

Model 1 is a linear mixed effects model, according to the formula [1]:

Model 1 assumes fixed coefficients and considers a random subject-specific intercept that accounts for the repeated measurements per subject.

Model 2 is a conventional power-law model that took into account the rates of B-cell decay (1, 2), which is defined as:

where is the log antibody titer at time post-vaccination, is the peak log level, is the decay rate, and is an arbitrary small constant that was often set to zero. The parameters and were assumed random effects and allowed to be patient-specific to account for individual variation.

Model 3 is a modified power-law model to account for activated and memory B-cells involved in a long-term antibody plateau [1, 2], using the following equation:

where (between 0 and 1) represents the proportion of antibodies that are produced in the long-term memory plateau [2]. The parameters and were random effects as in

Model 1 and was assigned as a fixed effect. All models were fitted using mixed model methodology (Nlmixed in SAS procedure).

[1] David MP, Van Herck K, Hardt K, Tibaldi F, Dubin G, Descamps D, et al. Long-

term persistence of anti-HPV-16 and -18 antibodies induced by vaccination with

the AS04-adjuvanted cervical cancer vaccine: modeling of sustained antibody

responses. Gynecologic oncology. 2009;115:S1-6.

[2] Fraser C, Tomassini JE, Xi L, Golm G, Watson M, Giuliano AR, et al. Modeling the long-term antibody response of a human papillomavirus (HPV) virus-like particle (VLP) type 16 prophylactic vaccine. Vaccine. 2007;25:4324-33. Figure S1 Flow chart of analysis Datasets. Dataset A (placebo recipients) was further divided into four subgroups according to anti-HEV levels at month 0: A1 (0.077≤GMC<0.25 WU/mL), A2

(0.25≤GMC<0.50 WU/mL), A3 (0.50≤GMC< 1.0 WU/mL) and A4 (GMC≥1.0 WU/mL). Table S1. Observed anti-HEV IgG persistence induced by natural HEV infection from months 0 to 67

Prevalence GMCs (95%CI) Dataset Time point No. samples No. positive (%) (WU/mL)

Dataset A (placebo recipients) Total Month 0 2242 2242 100 0.55(0.53-0.58) Month 7 1996 1966 99 0.52(0.49-0.54) Month 19 1852 1821 98 0.58(0.55-0.61) Month 31 1594 1545 97 0.46(0.43-0.48) Month 43 1635 1505 92 0.42(0.39-0.44) Month 67 1535 1280 83 0.27(0.26-0.29) Subgroup A1* Month 0 534 534 100 0.14(0.14-0.15) Month 7 473 444 94 0.14(0.13-0.14) Month 19 433 403 93 0.16(0.15-0.16) Month 31 376 330 88 0.12(0.12-0.13) Month 43 374 252 67 0.10(0.09-0.10) Month 67 346 120 35 0.07(0.06-0.07) Subgroup A2* Month 0 648 648 100 0.36(0.35-0.36) Month 7 576 576 100 0.34(0.33-0.35) Month 19 543 543 100 0.40(0.39-0.42) Month 31 458 458 100 0.30(0.29-0.32) Month 43 488 482 99 0.29(0.28-0.30) Month 67 461 437 95 0.22(0.21-0.23) Subgroup A3* Month 0 445 445 100 0.69(0.68-0.70) Month 7 395 394 100 0.66(0.63-0.69) Month 19 361 360 100 0.77(0.73-0.81) Month 31 315 312 99 0.55(0.52-0.58) Month 43 322 321 100 0.56(0.53-0.59) Month 67 296 292 99 0.36(0.35-0.38) Subgroup A4* Month 0 615 615 100 2.39(2.25-2.55) Month 7 552 552 100 2.12(1.98-2.28) Month 19 515 515 100 2.17(2.03-2.33) Month 31 445 445 100 1.82(1.69-1.97) Month 43 451 450 100 1.70(1.56-1.85) Month 67 432 431 100 0.93(0.86-1.00) * Grouped according to anti-HEV levels at month 0: A1 (0.077≤GMC<0.25 WU/mL), A2 (0.25≤GMC <0.50

WU/mL), A3 (0.50≤GMC< 1.0 WU/mL) and A4 (GMC≥1.0 WU/mL); Table S2. The observed anti-HEV IgG response of participants in Dataset B (vaccine

recipients) from months 0 to 67

Prevalence GMC (95%CI) Time point No. samples No. positive (%) (WU/mL) Total Month 0 2031 2031 100.00 0.53(0.51-0.56) Month 7 2031 2031 100.00 23.48(22.84-24.14) Month 19 1820 1819 99.95 7.46(7.18-7.76) Month 31 1626 1625 99.94 4.43(4.24-4.62) Month 43 1634 1631 99.82 3.73(3.57-3.89) Month 67 1539 1534 99.68 1.83(1.75-1.92) Subgroup B1* Month 0 1881 1881 100.00 0.53(0.50-0.56) Month 7 1881 1881 100.00 24.34(23.70-25) Month 19 1699 1698 99.94 7.58(7.29-7.89) Month 31 1521 1520 99.93 4.48(4.29-4.68) Month 43 1528 1525 99.80 3.73(3.57-3.90) Month 67 1444 1439 99.65 1.84(1.76-1.93) Subgroup B2* Month 0 27 27 100.00 0.44(0.26-0.73) Month 7 27 27 100.00 7.09(4.48-11.22) Month 19 23 23 100.00 3.96(2.27-6.89) Month 31 16 16 100.00 3.08(1.48-6.39) Month 43 18 18 100.00 2.95(1.59-5.49) Month 67 15 15 100.00 1.17(0.65-2.11) Subgroup B3* Month 0 56 56 100.00 0.67(0.5-0.89) Month 7 56 56 100.00 13.75(11.23-16.82) Month 19 44 44 100.00 5.98(4.52-7.9) Month 31 39 39 100.00 3.90(3.08-4.94) Month 43 43 43 100.00 4.13(3.23-5.27) Month 67 34 34 100.00 1.83(1.33-2.5) Subgroup B4* Month 0 67 67 100.00 0.59(0.43-0.80) Month 7 67 67 100.00 21.76(18.14-26.1) Month 19 54 54 100.00 7.16(5.54-9.24) Month 31 50 50 100.00 3.86(2.96-5.02) Month 43 45 45 100.00 3.57(2.68-4.76) Month 67 46 46 100.00 1.72(1.28-2.30) *Participants who received doses 1, 2 and 3 of Hecolin (Xiamen Innovax Biotech,China) were

grouped into subgroup B1; those who received only dose 1 were included in subgroup B2;

those who received doses 1 and 2 were included in subgroup B3; and those who received

doses 1 and 3 were included in subgroup B4.