Short-term dynamic changes in neutralizing antibodies against enterovirus 71 after vaccination

Figures & data

Table 1. Demographic characteristics of participants.

Characteristics	For participants sampling at Day 10 (N = 39)	For participants sampling at Day 20 (N = 39)	For participants sampling at Day 30 (N = 40)	For all participants (N = 118)
Boy, n (%)	12 (30.77)	23 (58.97)	19 (47.50)	54 (45.76)
Mean age in months (SD)	16.26 (8.26)	14.87 (8.31)	16.35 (9.01)	15.83 (8.50)
Mean height in cm (SD)	79.96 (8.68)	78.58 (8.89)	80.36 (9.14)	79.64 (8.86)
Mean weight in kg (SD)	10.51 (1.94)	10.20 (2.08)	10.65 (2.06)	10.46 (2.02)
Mean body mass index in kg/m^2 (SD)	16.49 (2.19)	16.47 (1.42)	16.47 (1.65)	16.48 (1.77)

Abbreviations: No., number of participants; SD, standard deviation; cm, centimeter; kg, kilogram; m, meter.

Figure 1. Trial profile.

Table 2. Immune response to EV71 vaccine after vaccination, in the per-protocol-set.

	For all participants (N = 104)			For participants sampling at day 10 (N = 37)			For participants sampling at day 20 (N = 31)			For participants sampling at day 30 (N = 36)
Variable	Pre-vaccine	30 days after two-dose injection	P value	Pre-vaccine	Post 1st vaccination	P value	Pre-vaccine	Post 1^st vaccination	P value	Pre-vaccine	Post 1st vaccination	P value	P value ^a
Proportion with titer ≥1:8, n, % (95% CI)	4, 3.85 (1.06–9.56)	104, 100.00 (96.52-)	<0.01	2, 5.41 (0.66–18.19)	33, 89.19 (74.58–96.97)	<0.01	1, 3.23 (0.08–16.70)	25, 80.65 (62.53–92.55)	<0.01	1, 2.78 (0.07–14.53)	24, 66.67 (49.03–81.44)	<0.01	0.06
Proportion with titer ≥1:16, n, % (95% CI)	4, 3.85 (1.06–9.56)	100, 96.15 (90.44–98.94)	<0.01	2, 5.41 (0.66–18.19)	20, 54.05 (36.92–70.51)	<0.01	1, 3.23 (0.08–16.70)	13, 41.94 (24.55–60.92)	<0.01	1, 2.78 (0.07–14.53)	11, 30.56 (16.35–48.11)	<0.01	0.13
GMT, value (95% CI)	4.97 (4.01–6.16)	97.13 (75.47–125.00)	<0.01	5.60 (3.47–9.06)	24.59 (14.06–43.02)^d	<0.01	4.78 (3.32–6.89)	12.85 (9.68–17.05)^de	<0.01	4.54 (3.51–5.87)	13.83 (8.07–23.71)^e	<0.01	0.048
Seroconversion rate ^a, n, % (95% CI)	-	102, 98.08 (93.23–99.77)	-	-	31, 83.78 (67.99–93.81)	-	-	24, 77.42 (58.90–90.41)	-	-	24, 66.67 (49.03–81.44)	-	0.23
Seroconversion rate ^b, n, % (95% CI)	-	102, 98.08 (93.23–99.77)	-	-	18, 48.68 (31.92–65.60)	-	-	13, 41.94 (24.55–60.92)	-	-	11, 30.56 (16.35–48.11)	-	0.28
GMI, value (95% CI)	-	19.5 (15.6–24.5)	-	-	4.39 (3.06–6.28)	-	-	2.69 (1.69–4.28)	-	-	3.05 (1.96–4.74)	-	0.22

Seroconversion was defined as either at least a 4-fold titer rise, or conversion from a negative baseline titer (with a titer below 1:8 for seroconversion rate ^a) to a titer of 1:32 or more, or conversion from a negative baseline titer (with a titer below 1:16 for seroconversion rate ^b) to a titer of 1:64 or more. Per-protocol-set was defined as participants who had correctly received two-dose vaccinations and had donated three blood samples at correct time point, with available antibody titer in all three serum.

Abbreviations: EV71, enterovirus type 71; CI, confidence interval; GMT, geometric mean titer; GMI, geometric mean increase.

^aP values here were from Kruskal-Wallis test among 3 groups in which the participants donated the second blood sample at different time points. Different characters ‘d, e’ were used to mark the post-vaccination GMT differences (d > e) by post hoc comparisons between different groups. See the small characters after 95% CI of each group.

Figure 2. Reverse cumulative curves for EV71 neutralizing antibody titers of participants included in the per-protocol-set on at pre-vaccination (day 0), post-first vaccination (day 10, day 20, and day 30), and 30 days post the second dose.

Table 3. Frequency of solicited adverse reactions within 30 days after injection of EV71 vaccine.

Symptom			Within 30 days after first dose	Within 30 days after second dose	Overall
Numbers of participants			118	113	118
Injection-site reactions
	Pain	N (%, [95%CI])	1 (0.85, [0.02–4.63])	1 (0.88, [0.02–4.83])	2 (1.69, [0.21–5.99])
	Induration	N (%, [95%CI])	6 (5.08, [1.89–10.74])	3 (2.65, [0.55–7.56])	8 (6.78, [2.97–12.92])
	Erythema	N (%, [95%CI])	9 (7.63, [3.55–13.99])	2 (1.77, [0.22–6.25])	10 (8.47, [4.14–15.03])
	Swelling	N (%, [95%CI])	1 (0.85, [0.02–4.63])	0 (0.00, [0.00–3.21])	1 (0.85, [0.02–4.63])
Overall
	Any	N (%, [95%CI])	12 (10.17, [5.37–17.09])	4 (3.54, [0.97–8.82])	14 (11.86, [6.64–19.10])
	Grade 3	N (%, [95%CI])	0 (0.00, [0.00–3.08])	0 (0.00, [0.00–3.21])	0 (0.00, [0.00–3.08])
Systemic reactions
	Fever	N (%, [95%CI])	30 (25.42, [17.86–34.26])	17 (15.04, [9.01–22.99])	41 (34.75, [26.22–44.06])
	Diarrhea	N (%, [95%CI])	13 (11.02, [6.00–18.10])	3 (2.65, [0.55–7.56])	16 (13.56, [7.95–21.08])
	Vomit	N (%, [95%CI])	4 (3.39, [0.93–8.45])	1 (0.88, [0.02–4.83])	5 (4.24, [1.39–9.61])
	Allergy	N (%, [95%CI])	2 (1.69, [0.21–5.99])	1 (0.88, [0.02–4.83])	2 (1.69, [0.21–5.99])
Overall
	Any	N (%, [95%CI])	44 (37.29, [28.56–46.67])	21 (18.58, [11.89–26.99])	56 (47.46, [38.19–56.85])
	Grade 3	N (%, [95%CI])	1 (0.85, [0.02–4.63])	0 (0.00, [0.00–3.21])	1 (0.85, [0.02–4.63])
All types
	Any	N (%, [95%CI])	50 (42.37, [33.33–51.81])	24 (21.24, [14.11–29.93])	61 (51.69, [42.31–60.99])
	Grade 3	N (%, [95%CI])	1 (0.85, [0.02–4.63])	0 (0.00, [0.00–3.21])	1 (0.85, [0.02–4.63])

Grade 1was defined as mild, i.e. no interference with activity; Grade 2 was defined as moderate, i.e. some interference with activity; Grade 3 was defined as severe, i.e. prevented activity.