A multicenter, single-blind, randomized, phase-2/3 study to evaluate immunogenicity and safety of a single intramuscular dose of biological E’s Vi-capsular polysaccharide-CRM₁₉₇ conjugate typhoid vaccine (TyphiBEV^TM) in healthy infants, children, and adults in comparison with a licensed comparator

Figures & data

Figure 1. Flow chart of subject disposition. n = number of subjects.

Table 1. Demographics and baseline characteristics-ITT population

Parameter/Statistics/Category	≥6 months to <2 years (N=282)		≥2 years to <18 years (N=170)		≥18 years to <64 years (N=170)		Overall (N=622)
	TyphiBEV^TM (N1=141)	Typbar-TCV (N1=141)	TyphiBEV^TM (N1=85)	Typbar-TCV (N1=85)	TyphiBEV^TM (N1=85)	Typbar-TCV (N1=85)	TyphiBEV^TM (N1=311)	Typbar-TCV (N1=311)
Gender, N1 (%)
Male	81 (57.45%)	66 (46.81%)	48 (56.47%)	51 (60.00%)	43 (50.59%)	40 (47.06%)	172 (55.31%)	157 (50.48%)
Female	60 (42.55%)	75 (53.19%)	37 (43.53%)	34 (40.00%)	42 (49.41%)	45 (52.94%)	139 (44.69%)	154 (49.52%)
Age (Years)
Mean	1.25	1.25	8.09	7.11	31.37	33.34	11.35	11.62
SD	0.38	0.41	4.33	3.77	7.41	8.71	13.39	14.44
Median	1.21	1.27	7.40	6.54	30.52	31.75	3.04	3.06
Range (Min:Max)	(0.59:1.98)	(0.52:1.99)	(2.06:17.36)	(2.01:15.96)	(19.00:49.56)	(18.30:53.85)	(0.59:49.56)	(0.52:53.85)
Height (Cms)
Mean	75.9	74.7	121.2	115.4	162.5	160.7	112.0	109.3
SD	7.05	7.10	27.20	24.30	10.10	9.76	39.54	38.59
Median	75.4	75.0	121.0	113.1	162.5	160.0	93.0	90.1
Range (Min:max)	(60.0:96.0)	(50.0:98.4)	(64.0:182.9)	(70.0:176.0)	(124.9:182.0)	(139.7:187.9)	(60.0:182.9)	(50.0:187.9)
Weight (Kgs)
Mean	9.5	9.5	25.7	22.1	63.2	60.0	28.6	26.7
SD	1.37	1.72	15.61	11.60	13.71	12.38	24.77	22.88
Median	9.5	9.5	20.3	19.5	60.0	59.2	12.5	13.0
Range (Min:Max)	(6.5:14.0)	(6.2:14.0)	(8.5:97.0)	(7.5:70.0)	(34.7:95.6)	(35.0:98.0)	(6.5:97.0)	(6.2:98.0)

ITT=intent-to-treat, Max=maximum, Min=minimum, N=sample size, N1=subject count, SD=standard deviation, Typbar-TCV=Bharat Biotech’s Typbar-Typhoid Vi-TT conjugate vaccine, TyphiBEV^TM =Biological E’s Typhoid Vi-CRM₁₉₇ conjugate vaccine.

Table 2. Summary of seroconversion (≥2 µg/ml) rates for Anti-Vi IgG antibody concentration by three age subsets and treatment groups-PP population

		≥6 months to <2 years (N1=259)			≥2 years to <18 years (N1=164)			≥18 years to <64 years (N1=168)				Overall (N=591)
Parameter	Anti-Vi IgG antibody concentration N1 (%) 95% CI	TyphiBEV^TM (N=129)	Typbar-TCV (N=130)	Proportion difference between groups (95% CI)	TyphiBEV^TM (N=82)	Typbar-TCV (N=82)	Proportion difference between groups (95% CI)	TyphiBEV^TM (N=84)	Typbar-TCV (N=84)	Proportion difference between groups (95% CI)	TyphiBEV^TM (N=295)	Typbar-TCV (N=296)	Proportion difference between groups (95% CI)
Pre-vaccination	Seroconverted (≥2 µg/mL)	7 (5.43%)	1 (.77%)		4 (4.88%)	2(2.44%)		3 (3.57%)	3(3.57%)		14 (4.75%)	6(2.03%)
	95% CI	2.21, 10.86	0.02, 4.21		1.34, 12.02	0.30, 8.53		0.74, 10.08	0.74, 10.08		2.62, 7.83	0.75, 4.36
	NotSeroconverted (<2 µg/mL)	122 (94.57%)	129(99.23%)		78 (95.12%)	80(97.56%)		81 (96.43%)	81(96.43%)		281 (95.25%)	290(97.97%)
Post-vaccination	Seroconverted (≥2 µg/mL)	128 (99.22%)	130(100.00%)	−0.78 (−2.29, 0.74)	82(100.00%)	81 (98.78%)	1.22 (−1.16, 3.60)	82 (97.62%)	83 (98.81%)	−1.19 (−5.19, 2.81)	292 (98.98%)	294 (99.32%)	−0.34 (−1.82, 1.14)
	95% CI	95.76, 99.98	97.20, 100.00		95.60, 100.00	93.39, 99.97		91.66, 99.71	93.54, 99.97		97.06, 99.79	97.58, 99.92
	Not Seroconverted (<2 µg/mL)	1 (0.78%)	0 (0.00%)		0 (0.00%)	1 (1.22%)		2 (2.38%)	1 (1.19%)		3 (1.02%)	2 (0.68%)

Percentages were calculated using respective column header count as denominator. 95% CI was calculated by Clopper–Pearson Method.

Two-sided 95% confidence intervals for difference in proportion of subjects between groups was calculated using pooled Z test.

CI=confidence interval, IgG=immunoglobulin G, N=sample Size, N₁=subject count, PP=per protocol, SD=standard deviation, Typbar-TCV=Bharat Biotech’s Typbar-Typhoid Vi-TT conjugate vaccine, TyphiBEV^TM =Biological E’s Typhoid Vi-CRM₁₉₇ conjugate vaccine.

Table 3. Summary of geometric mean concentrations for three age subsets by treatment groups-PP population

	≥6 months to <2 years (N1=259)			≥2 years to <18 years (N1=164)			≥18 years to <64 years (N1=168)			Overall (N=591)
Anti-Vi IgG antibody concentration	TyphiBEV^TM (N=129)	Typbar-TCV (N=130)	GMC Ratio (T/R)	TyphiBEV^TM (N=82)	Typbar-TCV (N=82)	GMC Ratio (T/R)	TyphiBEV^TM (N=84)	Typbar-TCV (N=84)	GMC Ratio (T/R)	TyphiBEV^TM (N=295)	Typbar-TCV (N=296)	GMC Ratio (T/R)
Pre-vaccination Parameters
N1	129	130		82	82		84	84		295	296
GMC	0.11	0.08	1.30	0.11	0.10	1.12	0.12	0.15	0.81	0.11	0.10
95% CI of GMC	(0.09, .13)	(0.07, 0.09)		(0.09, .13)	(0.08, .11)		(0.10, 0.15)	(0.12, 0.19)		(0.10, 0.12)	(0.09, 0.11)
Post vaccination Parameters
GMC	20.66	29.66	0.70	27.24	32.69	0.83	29.92	18.34	1.63	24.79	26.58	0.93
95% CI of GMC	(18.02, 23.69)	(26.88, 32.72)		(22.22, 33.40)	(27.14, 39.37)		(23.41, 38.23)	(15.12, 22.24)		(22.25,27.62)	(24.33, 29.05)

CI=confidence interval, GMC=geometric mean concentration, N₁=subject count, N=sample size, PP=per protocol, T/R=Test/Reference, Typbar-TCV=Bharat Biotech’s Typbar-Typhoid Vi-TT conjugate vaccine, TyphiBEV^TM =Biological E’s Typhoid Vi-CRM₁₉₇ conjugate vaccine.

Table 4. Fold increase of IgG antibody concentrations from baseline to Day 42 by vaccine group-PP population

Parameter (N=591/622)	Day 42 (Post Vaccination)
	TyphiBEV^TM (n=295)	Typbar-TCV (n=296)
≥4 Fold Rise	96.95% (286)	97.64% (289)
GMFR	223.38	260.81

GMFR=geometric mean fold rise, n=subject count, IgG= Immunoglobulin G, N=sample size, PP=per protocol, Typbar-TCV=Bharat Biotech’s Typbar-Typhoid Vi-TT conjugate vaccine, TyphiBEV^TM =Biological E’s Typhoid ViCRM₁₉₇ conjugate vaccine.

Figure 2. Local and systemic adverse events reported. TyphiBEV^TM =Biological E’s Typhoid Vi-CRM₁₉₇conjugate vaccine, Typbar-TCV=Bharat Biotech’s Typbar-Typhoid Vi-TTconjugate vaccine.