Immunological non-inferiority of a new fully liquid presentation of the MenACWY-CRM vaccine to the licensed vaccine: results from a randomized, controlled, observer-blind study in adolescents and young adults

Figures & data

Figure 1. Study highlights.

Figure 2. Trial profile and demographic characteristics of vaccinated study participants. PPI, per-protocol population for immunogenicity.

Table 1. Adjusted hSBA geometric mean titers (GMTs) 1-month post-vaccination and between-group ratios for groups that received MenACWY-CRM liquid vaccine aged for 24 or 30 months (ACWY_Liq24 and ACWY_Liq30) versus groups that received licensed MenACWY-CRM vaccine (ACWY_1 and ACWY_2) (per-protocol population for immunogenicity)

	ACWY_Liq24		ACWY_1		GMT ratio, ACWY_Liq24: ACWY_1 (95% CI)	ACWY_Liq30		ACWY_2		GMT ratio, ACWY_Liq30: ACWY_2 (95% CI)
	N	GMT (95% CI)	N	GMT (95% CI)		N	GMT (95% CI)	N	GMT (95% CI)
Overall
Serogroup A	363	386.66 (319.47–467.97)	373	318.34 (264.14–383.67)	1.21 (0.94–1.57)	356	387.06 (322.72–464.24)	349	348.89 (290.09–419.61)	1.11 (0.87–1.42)
Serogroup C	385	143.48 (110.49–186.30)	377	171.74 (131.74–223.87)	0.84 (0.58–1.19)	376	256.70 (195.29–337.41)	377	226.09 (171.62–297.85)	1.14 (0.79–1.64)
Serogroup W	372	62.63 (50.99–76.92)	388	66.37 (54.26–81.18)	0.94 (0.72–1.24)	374	83.23 (68.19–101.60)	366	75.42 (61.56–92.41)	1.10 (0.84–1.45)
Serogroup Y	379	115.66 (94.13–142.13)	390	106.47 (86.93–130.42)	1.09 (0.82–1.44)	386	112.38 (91.56–137.92)	377	117.56 (95.39–144.89)	0.96 (0.72–1.26)
Age 10–17 y
Serogroup A	154	441.33 (338.41–575.54)	153	422.96 (325.99–548.77)	1.04 (0.74–1.47)	151	397.32 (303.93–519.41)	138	382.73 (288.50–507.73)	1.04 (0.73–1.48)
Serogroup C	159	201.13 (137.19–294.88)	155	243.20 (165.65–357.06)	0.83 (0.51–1.35)	157	286.66 (181.94–451.65)	153	366.56 (230.68–582.47)	0.78 (0.44–1.40)
Serogroup W	150	40.72 (29.84–55.55)	158	51.38 (38.14–69.21)	0.79 (0.53–1.18)	151	71.12 (50.98–99.23)	146	57.61 (40.85–81.24)	1.23 (0.81–1.88)
Serogroup Y	157	109.92 (80.31–150.46)	157	112.85 (82.99–153.44)	0.97 (0.65–1.46)	155	123.01 (87.98–171.98)	154	92.01 (65.47–129.30)	1.34 (0.87–2.06)
Age 18–40 y
Serogroup A	209	362.33 276.85–474.18)	220	268.44 (206.90–348.30)	1.35 (0.94–1.94)	205	352.92 (273.22–455.86)	211	307.22 (238.98–394.94)	1.15 (0.82–1.61)
Serogroup C	226	106.05 (75.27–149.43)	222	125.38 (88.51–177.61)	0.85 (0.53–1.36)	219	221.98 (157.63–312.60)	224	156.43 (110.92–220.63)	1.42 (0.90–2.23)
Serogroup W	222	85.60 (64.97–112.79)	230	77.66 (59.13–102.00)	1.10 (0.76–1.61)	223	93.09 (71.32–121.52)	220	89.60 (68.42–117.33)	1.04 (0.73–1.48)
Serogroup Y	222	124.26 (94.11–164.08)	233	103.99 (79.17–136.58)	1.19 (0.82–1.75)	231	106.38 (81.03–139.65)	223	134.99 (102.20–178.30)	0.79 (0.55–1.13)

CI, confidence interval; GMT, geometric mean titer; N, number of participants who received vaccination and had assay results available; y, years of age.

Figure 3. Percentages of participants (with 95% confidence intervals) with (a,b) human serum bactericidal assay (hSBA) titer ≥8 at 1-month post-vaccination and (c,d) four-fold increase in hSBA titer from baseline to 1-month post-vaccination against serogroups A, C, W, and Y (per-protocol population for immunogenicity).

Four-fold increase in hSBA titer post-vaccination defined as four times the limit of detection (LOD) or the lower limit of quantitation (LLOQ) (whichever was greater) for individuals with pre-vaccination titers < LOD, four times the LLOQ for individuals with pre-vaccination titers between LOD and LLOQ (inclusive), or four times the pre-vaccination titer for individuals with pre-vaccination titers > LLOQ. LLOQ was 5 for MenA, 6 for MenC, 7 for MenW, and 6 for MenY, and LOD was 4 for each serogroup. ACWY_Liq24 group received investigational MenACWY-CRM liquid vaccine aged for 24 months; ACWY_Liq30 group received liquid vaccine aged for 30 months; ACWY_1 and ACWY_2 groups received licensed MenACWY-CRM vaccine. Number of participants with data available on hSBA titer ≥8 (serogroups A, C, W, Y, respectively): 378, 388, 389, 384 for ACWY_Liq24 group; 384, 382, 392, 392 for ACWY_1 group; 377, 379, 389, 393 for ACWY_Liq30 group; 367, 379, 384, 386 for ACWY_2 group. Number of participants with data available on four-fold increase in hSBA titer (serogroups A, C, W, Y, respectively): 363, 385, 372, 379 for ACWY_Liq24 group; 373, 377, 388, 390 for ACWY_1 group; 356, 376, 374, 386 for ACWY_Liq30 group; 349, 377, 366, 377 for ACWY_2 group. Percentage in ACWY_Liq24 and ACWY_1 groups with hSBA titer ≥8 at 1-month post-vaccination. Percentage in ACWY_Liq30 and ACWY_2 groups with hSBA titer ≥8 at 1-month post-vaccination. Percentage in ACWY_Liq24 and ACWY_1 group with four-fold increase in hSBA titer from baseline to 1-month post-vaccination. Percentage in ACWY_Liq30 and ACWY_2 groups with four-fold increase in hSBA titer from baseline to 1-month post-vaccination.

Figure 4. Percentages of participants reporting solicited local and systemic adverse events within 7 days of vaccination (solicited safety population).

Severe defined as preventing normal activity or, for loss of appetite, not eating at all. ACWY_Liq24 group received investigational MenACWY-CRM liquid vaccine aged for 24 months; ACWY_Liq30 group received liquid vaccine aged for 30 months; ACWY_1 and ACWY_2 groups received licensed MenACWY-CRM vaccine. N, number of participants.

Figure 5. Number (percentage) of participants reporting unsolicited adverse events (AEs) during the 1-month and 6-month post-vaccination periods (unsolicited safety population).

ACWY_Liq24 group received investigational MenACWY-CRM liquid vaccine aged for 24 months; ACWY_Liq30 group received liquid vaccine aged for 30 months; ACWY_1 and ACWY_2 groups received licensed MenACWY-CRM vaccine. N, number of participants.