Comparing the immunogenicity and safety of 3 Japanese encephalitis vaccines in Asia-Pacific area: A systematic review and meta-analysis

Figures & data

Figure 1. Flow diagram of study selection.

Table 1. Characteristics of the 3 Japanese Encephalitis vaccines included in the analysis

							Features used to assess quality oftrial reports according to the Jada questionaire^Citation32
First author	Year	Country	Vaccine type	No. of subjects	Published	RCT	Quality total score	Blinding	Dropouts and withdrawals	Generation of random numbers	Allocation concealment
Feroldi, E.^Citation16	2014	Thailand	JEV-L	301	Yes	Yes	4	1	1	1	1
Feroldi, E.^Citation17	2012	Thailand	JEV-L	1,200	Yes	Yes	3	1	0	1	1
Zhang, Z.H.^Citation24	2012	China	JEV-I(Vero)/JEV-L	285	Yes	Yes	3	1	0	1	1
Chokephaibulkit, K.^Citation13	2010	Thailand	JEV-L	300	Yes	Yes	3	1	0	1	1
Zhu. F.C.^Citation25	2008	China	JEV-I(PHK)/JEV-I(Vero)	480	No	Yes	5	0	2	2	1
Li, W.J.^Citation19	2007	China	JEV-I(Vero)/JEV-L	1,864	Yes	Yes	3	1	0	1	1
Yang, T.L.^Citation21	2005	China	JEV-I(PHK)/JEV-L	384	Yes	Yes	3	1	0	1	1
Zhang, H.R.^Citation23	2002	China	JEV-I(PHK)/JEV-L	264	Yes	Yes	4	1	1	1	1
Guo, S.H.^Citation18	2002	China	JEV-I(PHK)/JEV-I(Vero)/JEV-L	318	Yes	Yes	3	1	0	1	1
Yin, J.M.^Citation22	2002	China	JEV-I(PHK)/JEV-I(Vero)	309	Yes	Yes	3	1	0	1	1
Bai, Z.Y.^Citation11	2000	China	JEV-I(PHK)/JEV-L	160	Yes	Yes	4	2	0	1	1
Qu, S.W.^Citation20	2000	China	JEV-L	54	Yes	Yes	3	1	0	1	1
Chen. H.Y.^Citation12	1999	China	JEV-L	191	Yes	Yes	3	1	0	1	1
Dai, H.^Citation15	1997	China	JEV-I(PHK)	398	Yes	No	4	0	1	2	1
Dai, H.^Citation14	1994	China	JEV-I(PHK)	134	Yes	No	3	1	0	1	1

^a JEV-L, Japanese encephalitis live-attenuated vaccine;

^b JEV-I, Japanese Encephalitis inactivated vaccine;

^c Vero, Vero cells;

^d PHK, primary hamster kidney cells;

Table 2. Pooled analysis of seroconversion rates and adverse reaction rates

	Seroconversion		Adverse reaction
First author (Year)	Cases/total	Rate (95% CI)%	Cases/total	Rate (95% CI) %
JEV-I(PHK)Pooled	493/1,059	62.23 (58.31–66.26)	78/687	10.08 (7.74–12.42)
Zhu. F.C. (2008)^Citation25	71/80	88.75 (79.72–94.73)	18/160	11.25 (6.81–17.20)
Yang, T.L. (2005)^Citation21	104/161	64.60 (56.68–71.96)	42/176	23.86 (17.77–30.86)
Guo, S.H. (2002)^Citation18	17/35	48.57 (31.38–66.01)	3/114	2.63 (0.55–7.50)
Yin, J.M. (2002)^Citation22	24/35	68.57 (50.71–83.15)	5/114	4.39 (1.44–9.94)
Zhang, H.R. (2002)^Citation23	47/73	64.38 (52.31–75.25)	10/123	8.13 (3.97–14.44)
Bai, Z.Y. (2000)^Citation11	54/86	62.79 (51.70–72.98)	n.r.	n.r.
Dai, H. (1997)^Citation15	137/519	26.40 (22.65–30.41)	n.r.	n.r.
Dai, H. (1994)^Citation14	39/70	55.71 (43.34–67.59)	n.r.	n.r.
JEV-I(Vero)
Pooled	375/468	86.49 (83.64–89.36)	172/1731	12.49 (10.07–14.91)
Zhang, Z.H. (2012)^Citation24	87/143	60.84 (52.33–68.89)	12/143	8.39 (4.75–15.23)
Zhu. F.C. (2008)^Citation25	146/160	91.25 (85.76–95.13)	28/320	8.75 (5.89–12.40)
Li, W.J. (2007)^Citation19	78/101	77.23 (67.82–84.98)	91/1040	8.75 (7.10–10.63)
Guo, S.H. (2002)^Citation18	32/32	100.00 (89.11–100.00)	20/105	19.05 (12.04–27.87)
Yin, J.M. (2002)^Citation22	32/32	100.00 (89.11–100.00)	21/105	20.00 (12.83–28.93)
JEV-L
Pooled	822/972	83.52 (80.90-86.14)	825/2,457	18.09 (15.83–20.35)
Feroldi, E. (2014)^Citation16	239/249	95.98 (92.74–98.06)	n.r.	n.r.
Feroldi, E. (2012)^Citation17	187/199	93.97 (89.70–96.85)	729/1,097	66.45 (63.57–69.25)
Zhang, Z.H. (2012)^Citation24	128/142	90.14 (84.01–94.50)	14/142	9.86 (5.50–15.99)
Chokephaibulkit, K. (2010)^Citation13	87/98	88.78 (80.80–94.26)	n.r.	n.r.
Li, W.J. (2007)^Citation19	70/92	76.09 (66.06–84.37)	43/824	5.22 (3.80–6.97)
Yang, T.L. (2005)^Citation21	169/191	88.48 (83.08–92.64)	22/208	10.58 (6.75–15.58)
Zhang, H.R. (2002)^Citation23	63/69	91.30 (82.03–96.74)	12/141	8.51 (4.48–14.39)
Guo, S.H. (2002)^Citation18	20/29	68.97 (49.17–84.72)	n.r.	n.r.
Bai, Z.Y. (2000)^Citation11	91/109	83.49 (75.16–89.91)	n.r.	n.r.
Qu, S.W. (2000)^Citation20	38/54	70.37 (56.39–82.02)	5/45	11.11 (3.71–24.05)
Chen. H.Y. (1999)^Citation12	56/87	64.37 (53.38–74.35)	n.r.	n.r.

^a JEV-I, Japanese Encephalitis inactivated vaccine;

^b PHK, primary hamster kidney cells;

^c n.r., not reported in the study;

^d Vero, Vero cells;

^e JEV-L, Japanese encephalitis live-attenuated vaccine.

Table 3. Comparison of seroconversion and adverse events among JEV-I(Vero), JEV-I(PHK), and JEV-L

	Seroconversion					Adverse reactions
	Cases/total				Cases/total
First author (Year)	JEV-I(Vero)	JEV-I(PHK)	Weight %	RR (95% CI)	JEV-I(Vero)	JEV-I(PHK)	Weight %	RR (95% CI)
Pooled	210/224	112/150	100.00	1.36 (1.21–1.53)	69/530	26/530	100.00	2.31 (1.43–3.76)
Zhu, F.C. (2008)^Citation25	146/160	71/80	45.45	1.03 (0.94–1.13)	28/320	18/160	45.45	0.78 (0.44–1.36)
Guo, S.H. (2002)^Citation18	32/32	17/35	27.27	2.03 (1.44–2.84)	20/105	3/144	27.27	7.24 (2.21–23.65)
Yin, J.M. (2002)^Citation22	32/32	24/35	27.27	1.45 (1.15–1.82)	21/105	5/114	27.27	4.56 (1.78–11.66)
Test of RR = 1				Z = 5.05/P < 0.001				Z = 3.40/P = 0.001
	JEV-L	JEV-I(PHK)			JEV-L	JEV-I(PHK)
Pooled	343/398	222/355	100.00	1.38 (1.23–1.56)	39/394	55/413	100.00	1.23 (0.71–2.12)
Yang, T.L. (2005)^Citation21	169/191	104/161	21.43	1.37 (1.21–1.55)	22/208	42/176	30.00	0.44 (0.28–0.71)
Zhang,H.R.(2002)^Citation23	63/69	47/73	28.57	1.42 (1.18–1.71)	12/141	10/123	40.00	1.05 (0.47–2.34)
Guo, S.H. (2002)^Citation18	20/29	17/35	21.43	1.42 (0.93–2.16)	5/45	3/114	30.00	4.22 (1.05–16.94)
Bai, Z.Y. (2000)^Citation11	91/109	54/86	28.57	1.33 (1.11–1.60)	n.r.	n.r.	—	—
Test of RR = 1				Z = 5.30/P < 0.001				Z = 0.74/P = 0.458
	JEV-L	JEV-I(Vero)			JEV-L	JEV-I(Vero)
Pooled	218/263	197/276	100.00	1.00 (0.90–1.12)	62/1,011	123/1,288	100.00	0.74 (0.49–1.12)
Zhang,Z.H.(2012)^Citation24	128/142	87/143	33.33	1.48 (1.29–1.71)	14/142	12/143	33.33	1.17 (0.56–2.45)
Li, W.J. (2007)^Citation19	70/92	78/101	33.33	0.99 (0.84–1.15)	43/824	91/1,040	33.33	0.60 (0.42–0.85)
Guo, S.H. (2002)^Citation18	20/29	32/32	33.33	0.69 (0.54–0.89)	5/45	20/105	33.33	0.58 (0.23–1.46)
Test of RR = 1				Z = 0.08/P0.939				Z = 1.43/P < 0.196

^a JEV-I, Japanese Encephalitis inactivated vaccine;

^b Vero, Vero cells;

^c PHK, primary hamster kidney cells;

^d α' = 0.0167;

^e JEV-L, Japanese encephalitis live-attenuated vaccine.

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