Safety and immunogenicity of a combined Tetanus, Diphtheria, recombinant acellular Pertussis vaccine (TdaP) in healthy Thai adults

Figures & data

Figure 1. Subjects Disposition.

Table 1. Summary of demographics at baseline by vaccine group.

Demographics at  baseline (Screening day)	BNA's aP	BNA's TdaP	Adacel®	Total	P-value
Gender: n (%)					0.81 [1]
-Male	10 (50.00)	9 (45.00)	11 (55.00)	30 (50.00)
-Female	10 (50.00)	11 (55.00)	9 (45.00)	30 (50.00)
Age					0.60 [2]
-N	20	20	20	60
-Mean (SD)	28.23 (4.67)	27.00 (4.63)	28.30 (4.31)	27.85 (4.50)
-Min/Max	18.87 – 34.93	18.29 – 35.86	20.85 – 34.34	18.29 – 35.86
Height (m)
-N	20	20	20	60	0.65 [2]
-Mean (SD)	1.62 (0.09)	1.64 (0.08)	1.62 (0.06)	1.63 (0.08)
-Min/Max	1.52 – 1.84	1.52 – 1.75	1.52 – 1.74	1.52 – 1.84
Weight (kg)
-N	20	20	20	60	0.18 [2]
-Mean (SD)	59.11 (9.89)	63.74 (13.78)	66.38 (13.14)	63.07 (12.55)
-Min/Max	41.80 – 79.50	44.50 – 90.30	44.40 – 89.40	41.80 – 90.30

Note. [1] P-value based on Chi-square test. [2] P-value based on One-way ANOVA.

Table 2. Local and systemic reactions during 7 d after vaccination by vaccine group.

	Visit 2 (Vaccination)				Visit 3 (Day 1)				Visit 4 (Day 7)
	BNA's aP	BNA's TdaP	Adacel®		BNA's aP	BNA's TdaP	Adacel®		BNA's aP	BNA's TdaP	Adacel®
Local andSystemicReactions	n (%)	n (%)	n (%)	P-value	n (%)	n (%)	n (%)	P- value	n (%)	n (%)	n (%)	P-value
Local
Pain	12 (60.00)	13 (65.00)	13 (65.00)	—	16 (80.00)	15 (75.00)	16 (80.00)	—	16 (80.00)	15 (75.00)	17 (85.00)	0.73
	(38.53–81.47)	(44.10–85.90)	(44.10–85.90)		(62.47–97.53)	(60.62–97.28)	(67.81–100.00)		(62.47–97.53)	(56.02–93.98)	(69.35–100.00)
Redness	0 (0.00)	0 (0.00)	1 (5.00)	—	0 (0.00)	3 (15.00)	1 (5.00)	0.12	0 (0.00)	3 (15.00)	1 (5.00)	0.15
	(0.00–0.00)	(0.00–0.00)	(0.00–14.55)		(0.00–0.00)	(0.00–32.19)	(0.00–15.30)		(0.00–0.00)	(0.00–30.65)	(0.00–14.55)
Induration	0 (0.00)	1 (5.00)	0 (0.00)	—	0 (0.00)	4 (20.00)	1 (5.00)	0.04^*	0 (0.00)	4 (20.00)	1 (5.00)	0.06
	(0.00–0.00)	(0.00–14.55)	(0.00–0.00)		(0.00–0.00)	(2.72–39.38)	(0.00–15.30)		(0.00–0.00)	(2.47–37.53)	(0.00–14.55)
Systemic
Fever	0 (0.00)	0 (0.00)	0 (0.00)		0 (0.00)	0 (0.00)	1 (5.00)	0.66	0 (0.00)	0 (0.00)	1 (5.00)	—
	(0.00–0.00)	(0.00–0.00)	(0.00–0.00)		(0.00–0.00)	(0.00–0.00)	(0.00–15.30)		(0.00–0.00)	(0.00–0.00)	(0.00–14.55)
Headache	0 (0.00)	0 (0.00)	2 (10.00)	0.32	1 (5.00)	0 (0.00)	2 (10.00)	0.53	2 (10.00)	1 (5.00)	3 (15.00)	0.86
	(0.00–0.00)	(0.00–0.00)	(0.00–23.15)		(0.00–14.55)	(0.00–0.00)	(0.00–24.33)		(0.00–23.15)	(0.00–14.55)	(0.00–30.65)
Fatigue	2 (10.00)	0 (0.00)	2 (10.00)	0.53	2 (10.00)	2 (10.00)	5 (25.00)	0.28	3 (15.00)	2 (10.00)	5 (25.00)	0.43
	(0.00–23.15)	(0.00–0.00)	(0.00–23.15)		(0.00–23.15)	(0.00–24.33)	(6.52–46.12)		(0.00–30.65)	(0.00–23.15)	(6.02–43.98)
Arthralgia	1 (5.00)	0 (0.00)	1 (5.00)	—	1 (5.00)	1 (5.00)	2 (10.00)	0.84	1 (5.00)	2 (10.00)	3 (15.00)	0.86
	(0.00–14.55)	(0.00–0.00)	(0.00–14.55)		(0.00–14.55)	(0.00–15.30)	(0.00–24.33)		(0.00–14.55)	(0.00–23.15)	(0.00–30.65)
Chills	1 (5.00)	0 (0.00)	0 (0.00)	—	1 (5.00)	0 (0.00)	1 (5.00)	—	1 (5.00)	0 (0.00)	1 (5.00)	—
	(0.00–14.55)	(0.00–0.00)	(0.00–0.00)		(0.00–14.55)	(0.00–0.00)	(0.00–15.30)		(0.00–14.55)	(0.00–0.00)	(0.00–14.55)
Malaise	1 (5.00)	0 (0.00)	1 (5.00)	—	1 (5.00)	1 (5.00)	4 (20.00)	0.30	1 (5.00)	1 (5.00)	5 (25.00)	0.08
	(0.00–14.55)	(0.00–0.00)	(0.00–14.55)		(0.00–14.55)	(0.00–15.30)	(2.72–39.38)		(0.00–14.55)	(0.00–14.55)	(6.02–43.98)
Myalgia	1 (5.00)	1 (5.00)	2 (10.00)	—	4 (20.00)	2 (10.00)	7 (35.00)	0.14	5 (25.00)	2 (10.00)	7 (35.00)	0.21
	(0.00–14.55)	(0.00–14.55)	(0.00–23.15)		(2.47–37.53)	(0.00–24.33)	(15.15–58.53)		(6.02–43.98)	(0.00–23.15)	(14.10–55.90)
Vomiting	0 (0.00)	0 (0.00)	0 (0.00)	—	0 (0.00)	0 (0.00)	0 (0.00)	—	0 (0.00)	0 (0.00)	0 (0.00)	—
	(0.00–0.00)	(0.00–0.00)	(0.00–0.00)		(0.00–0.00)	(0.00–0.00)	(0.00–0.00)		(0.00–0.00)	(0.00–0.00)	(0.00–0.00)

P-value based on Fisher's exact,

* P < 0.05, statistically significant.

Table 3A. Seroresponse rates as defined by the percentage of subjects with ≥ 4-fold increase as compared to baseline values of anti-PT IgG, anti-FHA IgG, anti-PRN IgG and anti-PT neutralizing antibody titers at 7 and 28 d after vaccination.

	Day 7				Day 28
	BNA's aP	BNA's TdaP	Adacel®		BNA's aP	BNA's TdaP	Adacel®
	N = 19	18	19		19	18	19
	n (%) (95% CI)	n (%) (95% CI)	n (%) (95% CI)	P-value	n (%) (95% CI)	n (%) (95% CI)	n (%) (95% CI)	P-value
Anti-PT ELISA	9 (47.37) (25.0–70.0)	8 (44.44) (21.0–67.0)	11 (57.89) (36.0–80.0)	0.688 [1]	17 (89.47) (76.0–100.0)	17 (94.44) (84.0–100.0)	16 (84.21) (68.0–100.0)	0.862 [2]
Anti- FHA ELISA	16 (84.21) (68.0–100.0)	14 (77.78) (59.0–97.0)	6 (31.58) (11.0–52.0)	0.001^* [1]	19 (100.00) (100.0–100.0)	17 (94.44) (84.0–100.0)	16 (84.21) (68.0–100.0)	0.209 [2]
Anti-PRN ELISA	9 (47.37) (25.0–70.0)	8 (44.44) (21.0–67.0)	11 (57.89) (36.0–80.0)	0.688 [1]	15 (78.95) (61.0–97.0)	15 (83.33) (66.0–100.0)	16 (84.21) (68.0–100.0)	1.000 [2]
Anti-PT Nab	10 (52.63) (30.0–75.0)	12 (66.67) (45.0–88.0)	16 (84.21) (68.0–100.0)	0.110 [1]	17 (89.47) (76.0–100.0)	16 (88.89) (74.0–100.0)	16 (84.21) (68.0–100.0)	1.000 [1]

[1] Based on chi-square test, [2] Based on Fisher's exact,

* P < 0.05, statistically significant.

Figure 2. Percentages of subjects with cut-off value titers of ELISA and Nab anti-PT at baseline and 28 d after vaccination.

Table 3B. ELISA anti-PT, anti-FHA and anti-PRN IgG Geometric Mean Titers at baseline and 7 and 28 d after vaccination.

	PT			FHA			PRN
	Baseline	Day 7	Day 28	Baseline	Day 7	Day 28	Baseline	Day 7	Day 28
	GMT (IU/mL)(95% CI)	GMT (IU/mL)(95% CI)	GMT (IU/mL)(95% CI)	GMT (IU/mL)(95% CI)	GMT (IU/mL)(95% CI)	GMT (IU/mL)(95% CI)	GMT (IU/mL)(95% CI)	GMT (IU/mL)(95% CI)	GMT (IU/mL)(95% CI)
Vaccine
BNA's aP	6.98 (5.37–9.07)	31.38 (12.92–76.24)	264.0^b (113.70–612.92)	12.57 (8.27–19.11)	130.2^b (78.59–215.62)	728.0^b (545.94–970.66)	9.20 (5.84–14.47)	28.77 (11.95–69.31)	120.4 (51.57–280.90)
BNA's TdaP	10.00 (5.78–17.31)	41.46 (17.67–97.29)	268.5^b (162.20–444.39)	15.50 (8.95–26.84)	154.0^b (102.66–230.90)	666.1^b (498.61–889.79)	7.91 (5.63–11.13)	29.73 (14.31–61.79)	118.3 (59.02–237.11)
Adacel®	6.77 (5.43–8.44)	25.98 (16.54–40.80)	50.79^a (36.98–69.75)	16.64 (11.05–25.05)	60.38^a (43.22–84.36)	159.6^a (114.49–222.49)	8.48 (6.33–11.37)	49.46 (21.32–114.75)	175.0 (77.51–395.11)
P-value	0.226	0.655	<0.001^*	0.640	0.004^*	<0.001^*	0.835	0.548	0.708

P-value based on One-way ANOVA,

* P < 0.05, statistically significant.

Table 4. Study vaccines composition.

Vaccine composition per  0.5-mL of individual dose	BNA's aP^*	BNA's TdaP^**	Adacel®^***
Active Ingredients
Tetanus Toxoid (TT)	—	7.5 Lf	5 Lf
Diphtheria Toxoid (DT)	—	2.0 Lf	2 Lf
Pertussis Toxoid (PT)	5 µg^****	5 µg^****	2.5 µg
Filamentous hemagglutinin (FHA)	5 µg	5 µg	5 µg
Pertactin (PRN)	2.5 µg	2.5 µg	3 µg
Fimbriae type 2/3	—	—	5 µg
Excipients
Aluminum content	0.3 mg	0.3 mg	0.33 mg

* Lot No. PER4001-1.

** Lot No. TDA4001-1.

*** Lot U4700BA.

**** containing PTgen.