The investigational meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (ACWY-TT) and the seasonal influenza virus vaccine are immunogenic and well-tolerated when co-administered in adults

Figures & data

Table 1. Evaluation of primary non-inferiority hypotheses and exploratory analyses: Coad group vs. ACWY-TT and MenPS groups (ATP Influenza cohort for immunogenicity)

Antibody	N	Adjusted GMT	N	Adjusted GMT	Adjusted GMT ratio (95% CI)
	ACWY-TT		Coad		(ACWY-TT/Coad)**
rSBA-MenA	263	3895.9	85	2860.8	1.36 (1.04; 1.78)
rSBA-MenC	293	10299.7	97	6908.0	1.49 (1.10; 2.03)
rSBA-MenW-135	299	5848.2	101	4770.5	1.23 (0.91; 1.65)
rSBA-MenY	300	7331.2	102	5617.2	1.31 (1.00; 1.70)
	MenPS		Coad		(MenPS/Coad)
rSBA-MenA	88	1794.3	85	2860.8	0.63 (0.45; 0.87)
rSBA-MenC	101	9032.1	97	6908.0	1.31 (0.90; 1.90)
rSBA-MenW-135	102	2639.6	101	4770.5	0.55 (0.39; 0.80)
rSBA-MenY	100	3385.8	102	5617.2	0.60 (0.43; 0.84)
	Vaccine response				Difference between groups
	N*	%VR	N*	%VR	% (95% CI)
	Coad		ACWY-TT		(Coad minus ACWY-TT)
rSBA-MenA	85	76.5	263	80.6	-4.14 (-15.12; 5.27)
rSBA-MenC	97	88.7	293	89.1	-0.42 (-8.85; 6.04)
rSBA-MenW-135	101	88.1	299	92.0	-3.85 (-12.05; 2.32)
rSBA-MenY	102	81.4	300	86.3	-4.96 (-14.30; 2.79)
	Coad		MenPS		(Coad minus MenPS)
rSBA-MenA	85	76.5	88	63.6	12.83 (-0.88; 26.13)
rSBA-MenC	97	88.7	101	87.1	1.53 (-7.94; 10.97)
rSBA-MenW-135	101	88.1	102	87.3	0.86 (-8.52; 10.26)
rSBA-MenY	102	81.4	100	73.0	8.37 (-3.26; 19.96)

N, number of subjects with available results; N*, number of subjects with both pre and post results available; % VR, percentage of subjects with a vaccine response defined as: For initially seronegative subjects, post-vaccination antibody titer ≥ 1:32; For initially seropositive subjects, post-vaccination titer ≥ 4-fold the pre-vaccination titer. 95% CI, 95% confidence interval; Bold, upper limit of 95% CI is below the pre-defined limit of 2.0 for the adjusted GMT ratios—(ANCOVA model: adjustment for age strata, baseline titer -pooled variance with more than 2 groups); **primary non-inferiority objective, all other comparisons were exploratory. Adjusted GMT, geometric mean antibody titer adjusted for age strata and baseline titer

Figure 1. rSBA GMTs in each group one month after vaccination (ATP Influenza cohort for immunogenicity). *statistically significant difference between the indicated group and the Coad group: differences between groups were done on GMT values adjusted for pre-vaccination measurements and age strata, exploratory analysis, whereas the GMTs displayed are unadjusted.

Figure 2. Reverse cumulative curves showing rSBA titers for N. meningitidis serogroups A, C, W-135 and Y. ACWY+F, Coad group; ACWY_F, ACWY-TT group; MenPS_F, MenPS group

Table 2. Influenza humoral immune responses one month after vaccination (ATP Influenza cohort for immunogenicity)

Influenza	Time	Seroconversion rate			Seroconversion factor			Anti-haemagglutination inhibition antibodies
strain	point	N	%	(95% CI)	N	%	(95% CI)	N	% ≥ 1:40	(95% CI)	GMT	(95% CI)
A/H1N1	Pre	-	-	-	-	-	-	105	64.8	(54.8; 73.8)	54.1	(43.0; 68.1)
	Post	105	71.4	(61.8; 79.8)	105	9.9	(7.5; 13.1)	105	99.0	(94.8; 100)	537.2	(446.9; 645.8)
A/H3N2	Pre	-	-	-	-	-	-	105	54.3	(44.3; 64.0)	31.5	(25.1; 39.6)
	Post	105	61.9	(51.9; 71.2)	105	5.6	(4.4; 7.2)	105	97.1	(91.9; 99.4)	177.8	(150.0; 210.7)
B	Pre	-	-	-	-	-	-	103	42.7	(33.0; 52.8)	20.9	(17.0; 25.7)
	Post	103	75.7	(66.3; 83.6)	103	9.1	(7.1; 11.6)	104	96.2	(90.4; 98.9)	192.7	(156.4; 237.6)

N, number of subjects with available results (for seroconversion rate and seroconversion factor N, the number of subjects with pre- and post-vaccination results available). %, percentage of subjects the indicated endpoint; 95% CI, 95% confidence interval; Seroconversion: For initially seronegative subjects (i.e., anti-HI titers < 1:10), antibody titer ≥ 1:40 after vaccination. For initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. Seroconversion factor, geometric mean ratio [mean(log₁₀(post-vaccination GMT/ pre vaccination GMT)]. Pre, prior to vaccination, Post, one month post vaccination. CHMP criteria for success¹⁴: the lower limit of the two-sided exact 95% CI in the seroconversion rate is > 40% or the lower limit of the two-sided standardized asymptotic 95% CI in the fold increase in GMT is > 2.5, or the lower limit of the two-sided exact 95% CI in the proportion of subjects achieving an HI titer ≥ 40 is > 70.

Figure 3. Percentage of subjects reporting solicited local and general symptoms during the 4-day post-vaccination period (total vaccinated Influenza cohort). Note: For the Co-ad group, local symptoms refer to the percentage of subjects with at least one local symptom at either injection site. Gastrointestinal symptoms included nausea, vomiting, diarrhea and/or abdominal pain. Grade 3: Redness and swelling > 50mm, fever > 39.5°C, Preventing normal everyday activity for all other symptoms.

Nauta JJP, de Bruijn IA. The European CHMP criteria for influenza vaccine immunogenicity cannot be improved by the use of confidence intervals. Vaccine 2006; 24:6643 - 4; http://dx.doi.org/10.1016/j.vaccine.2006.05.053; PMID: 16797109

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