Immunogenicity and safety of a hexavalent pediatric vaccine in HIV-exposed infected and uninfected infants in Republic of South Africa

Figures & data

Figure 1. Disposition of study participants

Legend: N = number of subjects in population; FAS = full analysis set; noncompliance with protocol was nonattendance for vaccination or blood sampling and/or incomplete parental safety records.

Table 1. Seroprotection rates, seroconversion rates, and vaccine response rates pre- and post-primary series and booster vaccination (FAS)

		Group A (N = 14 [primary series], N = 12 [booster])				Group B (N = 49 [primary series], N = 40 [booster])
Antigen	Threshold	Pre-primary	Post-primary	Pre-booster	Post-booster	Pre-primary	Post-primary	Pre-booster	Post-booster
Hepatitis B	≥10 mIU/mL	NC	78.6 (49.2;95.3)	58.3 (27.7;84.8)	75.0 (42.8;94.5)	NC	100 (92.1;100)	85.0 (70.2;94.3)	100 (91.2;100)
	≥100 mIU/mL	NC	64.3 (35.1;87.2)	25.0 (5.5;57.2)	66.7 (34.9;90.1)	NC	84.4 (70.5;93.5)	27.5 (14.6;43.9)	90.0 (76.3;97.2)
Diphtheria	≥0.01 IU/mL	7.1 (0.2;33.9)	100 (75.3;100)	100 (73.5;100)	100 (73.5;100)	26.5 (14.9;41.1)	100 (92.1;100)	100 (91.2;100)	100 (91.2;100)
	≥0.10 IU/mL	0 (0;23.2)	100 (75.3;100)	66.7 (34.9;90.1)	100 (73.5;100)	0 (0:7.3)	100 (92.1;100)	95.0 (83.1;99.4)	100 (91.2;100)
	≥1.0 IU/mL	0 (0;23.2)	92.3 (64.0;99.8)	0 (0;26.5)	100 (73.5;100)	0 (0;7.3)	97.8 (88.2;99.9)	12.5 (4.2;26.8)	97.5 (86.8;99.9)
Tetanus	≥0.01 IU/mL	92.9 (66.1;99.8)	100 (75.3;100)	100 (73.5;100)	100 (73.5;100)	98.0 (89.1;99.9)	100 (92.1;100)	100 (91.2;100)	100 (91.2;100)
	≥0.10 IU/mL	64.3 (35.1;87.2)	100 (75.3;100)	75.0 (42.8;94.5)	100 (73.5;100)	79.6 (65.7;89.8)	100 (92.1;100)	75.0 (58.8;87.3)	100 (91.2;100)
	≥1.0 IU/mL	21.4 (4.7;50.8)	76.9 (46.2;95.0)	8.3 (0.2;38.5)	91.7 (61.5;99.8)	36.7 (23.4;51.7)	68.9 (53.4;81.8)	5.0 (0.6;16.9)	95.0 (83.1;99.4)
Polio 1	≥8 1/dil	NC	100 (75.3;100)	91.7 (61.5;99.8)	100 (73.5;100)	NC	100 (92.0;100)	100 (91.2;100)	100 (91.2;100)
Polio 2	≥8 1/dil	NC	100 (75.3;100)	75.0 (42.8;94.5)	100 (73.5;100)	NC	100 (92.0;100)	100 (91.2;100)	100 (91.2;100)
Polio 3	≥8 1/dil	NC	100 (75.3;100)	75.0 (42.8;94.5)	100 (73.5;100)	NC	100 (91.8;100)	100 (91.2;100)	100 (91.2;100)
Pertussis
PT	≥LLOQ	35.7 (12.8;64.9)	100 (75.3;100)	91.7 (61.5;99.8)	100 (73.5;100)	55.1 (40.2;69.3)	100 (92.1;100)	100 (91.2;100)	100 (91.2;100)
	≥4x LLOQ^a	14.3 (1.8;42.8)	100 (75.3;100)	75.0 (42.8;94.5)	100 (73.5;100)	12.2 (4.6;24.8)	100 (92.1;100)	67.5 (50.9;81.4)	100 (91.2;100)
	VR^b	NA	100 (75.3;100)	NA	100 (73.5;100)	NA	100 (92.1;100)	NA	100 (91.2;100)
	Seroconversion^c	NA	92.3 (64.0;99.8)	NA	91.7 (61.5;99.8)	NA	91.1 (78.8;97.5)	NA	92.5 (79.6;98.4)
	Booster response^d	NA	NA	NA	100 (73.5;100)	NA	NA	NA	100 (91.2;100)
FHA	≥LLOQ	71.4 (41.9;91.6)	100 (75.3;100)	100 (73.5;100)	100 (73.5;100)	89.8 (77.8;96.6)	100 (92.1;100)	100 (91.2;100)	100 (91.2;100)
	≥4x LLOQ^a	21.4 (4.7;50.8)	100 (75.3;100)	100 (73.5;100)	100 (73.5;100)	57.1 (42.2;71.2)	100 (92.1;100)	95.0 (83.1;99.4)	100 (91.2;100)
	VR^b	NA	100 (75.3;100)	NA	100 (73.5;100)	NA	100 (92.1;100)	NA	95.0 (83.1;99.4)
	Seroconversion^c	NA	100 (75.3;100)	NA	100 (73.5;100)	NA	86.7 (73.2;94.9)	NA	80.0 (64.4;90.9)
	Booster response^d	NA	NA	NA	75.0 (42.8;94.5)	NA	NA	NA	85.0 (70.2;94.3)
PRP	≥0.15 µg/mL	NC	92.9 (66.1;99.8)	58.3 (27.7;84.8)	100 (73.5;100)	NC	97.7 (88.0;99.9)	76.9 (60.7;88.9)	100 (91.2;100)
	≥1 µg/mL	NC	78.6 (49.2;95.3)	25.0 (5.5;57.2)	91.7 (61.5;99.8)	NC	75.0 (59.7;86.8)	30.8 (17.0;47.6)	97.5 (86.8;99.9

Data are % (95% CI) participants with titer or concentration above threshold.

Group A: HIV-exposed infected.

Group B: HIV-exposed uninfected.

^aFrom pre-primary to post-primary, and pre-booster to post-booster.

^bFor primary series: post-primary series concentration ≥4x LLOQ if pre-primary series concentration <4x LLOQ, or post-primary series concentration ≥pre-primary series concentration if pre-primary series concentration ≥4x LLOQ; for booster: post-booster concentration ≥4-fold increase from pre-primary series if pre-primary series concentration <4x LLOQ, or post-booster vaccination ≥2-fold increase from pre-primary series concentration if pre-primary series concentration ≥4x LLOQ.

^c≥4-fold increase in concentration from pre-primary series to post-primary series or post-booster

^dPost-booster concentration ≥4-fold increase from pre-booster if pre-booster vaccination concentration <4x LLOQ, or post-booster vaccination ≥2-fold increase from pre-booster vaccination concentration if pre-booster concentration ≥4x LLOQ.

VR = vaccine response; NA = not applicable; NC = not calculated.

Table 2. Geometric mean concentrations and titers pre- and post-primary series and booster vaccination (FAS)

		Group A (N = 12)				Group B (N = 40)
Antigen	Threshold	Pre-primary	Post-primary	Pre-booster	Post-booster	Pre-primary	Post-primary	Pre-booster	Post-booster
Hepatitis B	GMC (mIU/mL)	NC	152(32.4;717)	21.7(6.12;77.2)	306(32.6;2875)	NC	222(147;335)	36.2(23.5;55.8)	1713(920;3187)
Diphtheria	GMC (IU/mL)	0.003(0.002;0.005)	3.40(2.02;5.71)	0.229(0.113;0.462)	7.88(4.29;14.5)	0.005(0.004;0.007)	2.80(2.44;3.21)	0.389(0.292;0.519)	5.25(4.18;6.59)
Tetanus	GMC (IU/mL)	0.140(0.043;0.455)	3.19(1.47;6.91)	0.219(0.084;0.569)	7.77(3.23;18.7)	0.397(0.246;0.640)	1.38(1.07;1.79)	0.179(0.131;0.245)	4.74(3.54;6.36)
Polio 1	GMT 1/dil	NC	1448(444;4721)	144(28.8;715)	2299(821;6439)	NC	1567(1183;2075)	287(178;461)	3051(2173;4283)
Polio 2	GMT 1/dil	NC	1841(615;5509)	108(18.2;637)	3545(1260;9978)	NC	1448(1075;1951)	208(142;305)	5997(4384;8203)
Polio 3	GMT 1/dil	NC	1611(529;4902)	80.7(17.7;369)	2233(781;6384)	NC	2311(1719;3108)	267(180;397)	4787(3165;7242)
Pertussis
PT	GMC (EU/mL)	1.80(1.09;2.99)	200(121;331)	18.8(7.56;47.0)	225(113;445)	2.71(1.95;3.76)	151(129;176)	11.7(8.75;15.6)	171(135;216)
	GMCR^a	NA	118(48.6;289)	NA	11.9(5.69;25.0)	NA	53.1 (33.9;83.4)	NA	14.6(11.0;19.4)
FHA	GMC (EU/mL)	3.56(1.89;6.71)	470(233;948)	68.9(22.0;216)	397(200;791)	9.54(6.59;13.8)	310(258;371)	38.6(27.9;53.2)	193(145;257)
	GMCR^a	NA	150(63.1;357)	NA	5.77(2.78;12.0)	NA	32.7(19.7;54.6)	NA	5.00(3.87;6.48)
PRP	GMC (µg/mL)	NC	3.56(1.28;9.96)	0.294(0.082;1.06)	20.5(4.98;84.6)	NC	2.53(1.69;3.79)	0.469(0.285;0.771)	33.8(20.1;57.1)

Data are % (95% CI) participants with titer or concentration above threshold.

Group A: HIV-exposed infected.

Group B: HIV-exposed uninfected.

^aRatio of GMC (post-primary/pre-primary or post-booster/pre-booster).

NA = not applicable; NC = not calculated.

Table 3. Immediate, solicited, unsolicited, and serious adverse events during the study (SS)

		Group A (N = 14)^a			Group B (N = 49)^a
	Participants with at least one:	n/M	%	(95% CI)	n/M	%	(95% CI)
Primary series	Immediate unsolicited AE	0/14	0	(0;23.2)	0/49	0	(0;7.3)
	Solicited reaction	10/14	71.4	(41.9;91.6)	39/48	81.3	(67.4;91.1)
	Solicited injection site reaction	4/14	28.6	(8.4;58.1)	27/48	56.3	(41.2;70.5)
	Tenderness	4/14	28.6	(8.4;58.1)	27/48	56.3	(41.2;70.5)
	Erythema	0/14	0	(0;23.2)	2/48	4.2	(0.5;14.3)
	Swelling	0/14	0	(0;23.2)	5/48	10.4	(3.5;22.7)
	Solicited systemic reaction	10/14	71.4	(41.9;91.6)	35/48	72.9	(58.2;84.7)
	Grade 3
	Fever	2/14	14.3	(10.8;42.8)	3/48	6.3	(1.3;7.2)
	Vomiting	3/14	21.4	(4.7;50.8)	13/48	27.1	(15.3;41.8)
	Crying abnormal	7/14	50.0	(23.0;77.0)	30/48	62.5	(47.4;76.0)
	Drowsiness	4/14	28.6	(8.4;58.1)	19/48	39.6	(25.8;54.7)
	Appetite lost	6/14	42.9	(17.7;71.1)	10/48	20.8	(10.5;35.0)
	Irritability	5/14	35.7	(12.8;64.9)	24/48	50.0	(35.2;64.8)
	Unsolicited AE	7/14	50.0	(23.0;77.0)	29/49	59.2	(44.2;73.0)
	Unsolicited AR	0/14	0	(0;23.2)	0/49	0	(0;7.3)
	SAE	4/14	28.6	8.4;58.1)	1/49	2.0	(0.1;10.9)
	Death	0/14	0	(0;23.2)	0/49	0	(0;7.3)
Booster	Immediate unsolicited AE	0/12	0	(0;26.5)	0/40	0	(0;8.8)
	Solicited reaction	7/12	58.3	(27.7;84.8)	22/40	55.0	(38.5;70.7)
	Solicited injection site reaction	5/12	41.7	(15.2;72.3)	15/40	37.5	(22.7;54.2)
	Tenderness	4/12	33.3	(9.9;65.1)	14/40	35.0	(20.6;51.7)
	Erythema	0/12	0	(0;26.5)	1/40	2.5	(0.1;13.2)
	Swelling	1/12	8.3	(0.2;38.5)	0/40	0	(0;8.8)
	Extensive swelling of vaccinated limb	0/12	0	(0;26.5)	0/40	0	(0;8.8)
	Solicited systemic reaction	6/12	50.0	(21.1;78.9)	16/40	40.0	(24.9;56.7)
	Fever	3/12	25.0	(5.5;57.2)	1/40	2.5	(0.1;13.2)
	Vomiting	2/12	16.7	(2.1;48.4)	1/40	2.5	(0.1;13.2)
	Crying abnormal	5/12	41.7	(15.2;72.3)	12/40	30.0	(16.6;46.5)
	Drowsiness	0/12	0	(0;26.5)	7/40	17.5	(7.3;32.8)
	Appetite lost	4/12	33.3	(9.9;65.1)	11/40	27.5	(14.6;43.9)
	Irritability	3/12	25.0	(5.5;57.2)	10/40	25.0	(12.7;41.2)
	Unsolicited AE	0/12	0	(0;26.5)	10/40	25.0	(12.7;41.2)
	Unsolicited AR	0/12	0	(0;26.5)	0/40	0	(0;8.8)
	SAE	0/12	0	(0;26.5)	0/40	0	(0;8.8)
	Death	0/12	0	(0;26.5)	0/40	0	(0;8.8)

n, number of participants; N, number of participants in group; M, number of participants with available data; AE, adverse event; AR, adverse reaction; SAE, serious adverse eventGroup A: HIV-exposed infected.

Group B: HIV-exposed uninfected.

^aN = 12 (Group A) and N = 40 (Group B) for the booster vaccination.