Intradermal vaccination for infants and children

Figures & data

Table 1. Summary of efficacy and dose-sparing effect of ID vaccination, as compared with IM or SC vaccination, in infants and children.

					ID injection
Vaccine	Country	Year	Age	No. of subjects	Method	Dose	Comparison	Efficacy^*	Dose sparing	Reference
Trivalent inactivated influenza	China	2007	3 to <18 years	112	Mantoux	3 μg^#	15 μg IM	Comparable Seroprotection rates, fold increase in HAI GMT (95% CI) H1N1; 98% vs. 98%, 12.9 (7.9–21.4) vs. 11.1 (7.2–17.1) H3N2; 100% vs. 100%, 2.6 (2.1–3.4) vs. 4.5 (3.4–5.9)^§ B/Shanghai; 96% vs. 93%, 4.3 (3.2–5.8) vs. 4.4 (3.3–5.8)	Yes	34
	Japan	2008	6–12 months	34	Mantoux	3 μg	3 μg SC	Superior Positive titer rate, HAI titer ≥ 10 No. (%) H1N1; 14 (93.3) vs. 8 (47.1)^§ H3N2; 14 (93.3) vs. 14 (82.3) B/Shanghai; 11 (73.3) vs. 6 (35.3)^§	N/A	37
	China	2009	2–3 months	123	Mantoux	3 μg	7.5 μg IM	Comparable Fold increase in HAI GMT (95% CI) H1N1; 1.21 (1.02–1.43) vs. 1.13 (0.96–1.34) H3N2; 1.26 (1.07–1.46) vs. 1.26 (1.06–1.50) B/Malaysia; 1.15 (0.99–1.32) vs. 1.07 (0.94–1.22)	Yes	35
	Italy	2011	3–11 years	112	Microneedle device	9 μg, 15 μg	15 μg IM (with adjuvant)	Superior Seroprotection rates, fold increase in HAI GMT^** H1N1; 92.1% vs. 94.6% vs. 86.5%, 7.9 vs. 10.9 vs. 14.9 H3N2; 97.4% vs. 97.3% vs. 94.6%, 3.2 vs. 4.9 vs. 3.6 B/Brisbane; 55.3% vs. 62.2% vs. 32.4%^§, 2.4 vs. 8.6 vs. 1.9^§	Yes	36
Inactivated poliovirus	Oman	2010	2, 4, 6 months^¶	373	Needle-free jet injector	0.1 mL	0.5 mL IM	Similar seroconversion rates but lower titers Seroconversion rates, median titers (95% CI) Type1; 97.3% vs. 100%, 228 (144–287) vs. 724 (575–912)^§ Type 2; 95.7% vs. 100%^§, 287 (228–456) vs. 1149 (912–1,149)^§ Type 3; 97.9% vs. 100%, 362 (287–456) vs. ≥1,448 (≥1,448-≥1,448)^§	Yes	41
	Cuba	2010	6, 10, 14 weeks	364	Needle-free jet injector	0.1 mL	0.5 mL IM	Inferior Seroconversion rates, median titers (95% CI) Type1; 52.9% vs. 89.3%^§, 19 (19–22) vs. 85 (54–99)^§ Type 2; 85.0% vs. 95.5%^§, 45 (45–54) vs. 214 (178–295)^§ Type 3; 69.0% vs. 98.9%^§, 32 (24–45) vs. 295 (214–355)^§	Yes	47
	Philippines	2012	6, 10, 14 weeks, 15–18 months	224	Mantoux	0.1 mL	0.5 mL IM	Similar seroprotection rates but lower titers Seroprotective rates, GMT (95% CI) Type 1; 100% vs. 100%, 2,833 (2,392–3,356) vs. 6,666 (5,613–7,916) Type 2; 100% vs. 100%, 3,210 (2,672–3,857) vs. 6,522 (5,540–7,678) Type 3; 100% vs. 100%, 4,498 (3,608–5,607) vs. 11,952 (10,046–14,220)	Yes	46
	India	2012	6–9 months	869	Needle-free jet injector	0.1 mL	0.5 mL IM	Inferior Seroprevalence (95% CI), median titers (95% CI) Type 1; 100% (98–100) vs. 100% (98–100), ≥1,448 (≥1,448-≥1,448) vs. ≥1,448 (≥1,448-≥1,448^§ Type 2; 89% (83–93) vs. 99% (97–100)^§, 724 (455–910) vs. ≥1,448 (1,176-≥1,448)^§ Type 3; 70% (62–76) vs. 95% (90–97)^§, 202 (28–724) vs. 455 (181–910)^§	No	48
	Cuba	2013	4 and 8 months	310	Needle-free jet injector	0.1 mL	0.5 mL IM	Inferior Seroconversion rates, median titers (95% CI) Type1; 93.6% vs. 100%^§, 450 (357–566) vs. ≥1,448 (≥1,448-≥1,448)^§ Type 2; 98.1% vs. 100%, 898 (713-≥1,448) vs. ≥1,448 (≥1,448-≥1,448)^§ Type 3; 93.0% vs. 99.3%^§, 71 (36–113) vs. 898 (566-≥1,448)^§	Yes	51
	Cuba	2015	12–20 months	728	Needle-free jet injector	0.1 mL	0.5 mL IM	Inferior Seroprevalence, median titers (95% CI) Type 1; 98% vs. 98.6%, 1,423 (1,130–1,423) vs. 4,499 (3,573–5664) Type 2; 98.7% vs. 100%, 1,130 (898–1,130) vs. 2,839 (2,255–3,573) Type 3; 95.4% vs. 99.3%, 1,423 (898–1,791) vs. 4,499 (3,573–4,499)	N/A	49
	Bangladesh	2015	6, 14 weeks	308	Microneedle device	0.1 mL	0.5 mL IM	Inferior Seroconversion rates Type 1; 87.5% vs. 94.9% Type 2; 80.9% vs. 91% Type 3; 88.8% vs. 97.4%	N/A	50
Rabies virus	Thailand	1998	5–12 years	118	Mantoux	0.1 mL	0.5 mL IM	Similar seroprotection rates but lower titers Seroprotection rates, GMT (95% CI) 100% vs. 98.3%, 1.6 (1.2–2.0) vs. 3.5 (2.5–4.8)^§	Yes	60
	Thailand	2009	12–18 months	177	Mantoux	0.1 mL	0.5 mL, 1 mL IM	Similar seroprotection rates but lower titers Seroprotection rates, GMC (95% CI)^***100% vs. 100% vs. 100% vs. 100%, 13 (8–20), 25 (16–38), 161 (103–251), 190 (121–299)	Yes	61
Hepatitis B virus	United States	1994	Neonates	173	Mantoux	2 μg	2 μg, 10 μg IM	Inferior Seroprotection rates, GMC^****91% vs. 97% vs. 100%^§, 312 vs. 317 vs. 2,248^§	No	65
	Turkey	1998	Neonates, 3–6 years	367	Mantoux	2 μg	10 μg IM	Similar seroprotection rates but lower titers Seroprotection rates, GMT Neonates; 94% vs. 98%, 621 vs. 935 Children; 100% vs. 98%, 804 vs. 1,393	Yes	66
Hepatitis A virus	Thailand	2005	8–12 years	75	Mantoux	0.1 mL	0.25 mL IM	Similar seroprotection rates but lower titers Seroprotection rates, GMT (95% CI)100% vs. 100%, 542 (390–753) vs. 834 (664–1047)	Yes	69

^# Amount of hemagglutinin antigen per strain in influenza vaccine

^¶ Multiple ages in inactivated poliovirus vaccine category indicate multiple vaccinations at each time point for the same subjects

* ID vaccination vs. the comparison (IM or SC)

** ID 9 μg vs. ID 15 μg vs. IM

*** ID 2 doses vs. ID 3 doses vs. 0.5 mL IM vs. 1 mL IM

**** ID vs. 2 μg IM vs. 10 μg IM

^§ Statistically significant

Abbreviations: ID, intradermal; IM, intramuscular; SC, subcutaneous; HAI, hemaggulutination inhibition; GMT, geometric mean titer; GMC, geometric mean concentration; CI, confidence interval; N/A, not available

Table 2. Skin thickness in infants and children measured for intradermal vaccination by ultrasonography.

					Skin thickness
Authors	Country	Year	Age of subjects	No. of subjects	Deltoid	Suprascapular	Upper back	Lumbar	Reference
Ploin, et al.	France	2011	4–7, 12–18, 54–66 months	373^#	1.22 (1.01–1.41)	1.30 (1.08–1.49)	1.39 (1.20–1.57)*	1.31 (1.15–1.48)*	11
Saitoh, et al.	Japan	2015	2 months	78	1.67 (1.16–2.39)	1.83 (1.24–2.60)	N/A	N/A	12
			6 months	11	1.84 (1.52–2.29)	1.79 (1.57–2.14)
			13–15 years	82	1.81 (1.25–3.00)	2.43 (1.51–3.95)

Skin thickness is shown as mean (range) (mm).

^# Study subjects were infants aged 4–7 months (N = 118), children aged 12–18 months (N = 131), and children aged 54–66 months (N = 124). *Skin thickness at the upper back and lumbar sites was measured only in some children aged 54–66 months (N = 43).

Abbreviations: N/A, not available

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