Safety and immunogenicity of an adjuvanted Escherichia coli adhesin vaccine in healthy women with and without histories of recurrent urinary tract infections: results from a first-in-human phase 1 study

Figures & data

Table 1. Study cohorts and vaccination schedule

History of UTI	Cohort	Number of Subjects Enrolled	Vaccinations at Days 1, 30, 90, and 180	Volume of Injection^a
No^b	1	5	107 µg FimCH	0.5 mL
No^b	2	8	50 µg FimCH 10 µg adjuvant	0.3 mL
No^b	3 & 4	16	50 µg FimCH 20 µg adjuvant	0.3 mL
No^b	5	8	107 µg FimCH 40 µg adjuvant	0.3 mL
Yes^c	6	16	50 µg FimCH 40 µg adjuvant	0.3 mL
Yes^c	7	14	107 µg FimCH 43 µg adjuvant	0.5 mL

^aTwo different injection volumes were required to administer the appropriate dosages for each cohort because the vaccines were prepared from single concentrations of adjuvant drug product and FimCH drug product

^bNo history of UTI for the previous 24 months prior to study enrolment.

^cHistory of ≥5 UTIs in the last 24 months with at least one of these occurrences being documented as positive urine culture for E. coli at ≥10³ CFU/mL prior to study enrolment.

Table 2. UTI diagnosed by physicians with bacteria detected in midstream urine collections during the 19-month study

Subject No.	Study Day of Onset of UTI Symptoms	Recorded UTI Symptoms	≥10^3 CFU/mL identified from Urine Culture	If listed, bacteria identified fromurine culture was resistant to either TMP-SMX, FQ, NF, or CFTRX	Physician Prescribed Antibiotic(s)
COHORT 6
101–06-004	2	DFU	Enterococci	None	Macrobid®
	107	DFU	E. coli	TMP-SMX, FQ	Bactrim™ DS, Ceftin®
	284	U	E. coli	None	Ceftin®, Cipro®
	530	DU	E. coli	FQ, TMP-SMX	Bactrim™, Cipro® XR
101–06-005	158	DFU	E. coli	TMP-SMX	Macrobid®
101–06-007	Screen Visit	F	K. pneumoniae	NF	Cipro®
101–06-008	47	DFSU	Coag-neg staphylococci	FQ	Augmentin®
	162	F	Coag-neg staphylococci	FQ	Bactrim™ DS
	276	DH	Group B streptococci	None	Cipro®
	335	DF	Coag-neg staphylococci	FQ	Cipro®, Macrobid®
102–06-004	105	DS	E. coli	None	Macrobid®, sulfamethoxazole
102–06-005	6	DS	E. coli	FQ	Macrobid®
	27	D	Enterococci	None	Cipro®
	38	FU	E. coli	None	Sulfamethoxazole
103–06-001	196	DF	K. pneumoniae	TMP-SMX, NF, CFTRX	Macrobid®
105–06-002	34	DFU	K. pneumoniae	NF	Bactrim™
	436	FSU	Enterococci	None	Cipro®
106–06-001	251	DFSU	E. coli	None	Cipro®
106–06-002	38	U	E. coli	None	Cipro®
	112	DFU	E. coli	None	Cipro®
	143	FU	K. pneumoniae	NF	Cipro®
	208	DFU	K. pneumoniae	NF	Cipro®
	373	FU	E. coli	None	Cipro®
106–06-003	9	DU	E. coli	FQ	Azo Gantrisin®, Macrobid®
	52	DFU	E. coli	FQ, TMP-SMX	Cipro®
	70	DF	E. coli	FQ	Macrobid®
	97	FU	E. coli	FQ	Macrodantin®
	109	FU	E. coli	FQ	Macrobid®
	141	U	Enterococci	FQ	Macrobid®
	226	DFSU	E. coli	FQ, TMP-SMX	Macrobid®
	243	DFSU	E. coli	None	Cipro®
	293	DFU	E. coli	FQ, TMP-SMX	Bactrim™
	327	DFU	E. coli	FQ, TMP-SMX	Macrobid®
COHORT 7
101–07-004	Screen	DS	E. coli	FQ	Macrobid®
	14	DU	S. saprophyticus	None	Macrobid®
102–07-001	101	S	E. coli	TMP-SMX	Cipro®
	181	DH	E. coli	TMP-SMX	Cipro®
105–07-003	232	DFU	E. coli	None	Levaquin®
105–07-005	3	DFU	E. coli	None	Cipro®
	155	DFSU	E. coli	None	Cipro®
106–07-001	3	DFS	E. coli	None	Cipro®
	98	U	Coag-neg staphylococci	FQ	Cipro®
	215	FU	MUF	None	Cipro®
106–07-003	120	FU	E. coli	None	Macrobid®
106–07-007	23	DFU	E. coli	None	Cipro®
	57	DFU	E. coli	None	Cipro®
	110	DFSU	E. coli	None	Bactrim™
	118	DFSU	Citrobacter freundii	TMP/SMX	Cipro®
	156	FSU	K. pneumoniae	None	Cipro®
	325	DFSU	Enterococci	None	Cipro®
	415	DFS	Citrobacter group	None	Cipro®
107–07-003	Screen	FU	E. coli	FQ, TMP/SMX	Cipro®
	29	DFU	E. coli	FQ, TMP/SMX	Cipro®
	60	DU	E. coli	FQ, TMP/SMX	Augmentin®
	86	U	E. coli	FQ, TMP/SMX	Keflex®
	122	DH	E. coli	FQ, TMP/SMX	Cipro®
	177	FU	Enterococci	None	Cipro®
	213	FU	E. coli	FQ, TMP/SMX	Rocephin® IM
	235	DFU	K. pneumoniae	None	Zyvox®
	288	DFU	K. pneumoniae	None	Augmentin®
	428	FS	E. coli	None	Augmentin®
	486	DU	E. coli	FQ, TMP/SMX	Cipro®

D is dysuria; F is frequency; U is urgency; H is hematuria; S is suprapubic tenderness upon examination; coag-neg is coagulase-negative; group B streptococci is Streptococcus agalactiae; MUF is mixed urogenital flora; CFTRX is ceftriaxone; FQ are fluoroquinolones; NF is nitrofurantoin; TMP-SMX is trimethoprim sulfamethoxazole; Augmentin is amoxicillin/clavulanate potassium; azo gantrisin is phenazopyridine hydrochloride and sulfamethoxazole; Bactrim DS is TMP-SMX; Cipro is ciprofloxacin; Macrobid is NF; Macrodantin is NF; Rocephin IM is ceftriaxone intramuscular injection; Zyvox is linezolid; Keflex is cephalexin.

Table 3. Subject demographics

Characteristics	Cohort 1 N = 5	Cohort 2 N = 8	Cohort 3 N = 8	Cohort 4 N = 8	Cohort 5 N = 8	Cohort 6 N = 16	Cohort 7 N = 14
Age at vaccination, years
Mean	34	34	36	35	42	50	48
Min, max	27, 40	23, 56	24, 47	18, 48	22, 62	25, 64	23, 63
BMI, (kg/m^2)
Mean	28	26	26	33	26	26	26
Min, max	23, 35	19, 36	23, 44	17, 38	19, 39	24, 33	20, 30

Source: Sequoia Sciences; Data listing 16.2.4.1; Baseline Demographics Safety Population; BMI – body mass index.

Figure 1. Subject disposition

Table 4. Anti-FimH antibody responses for subjects in cohorts 1 to 7

	Cohort 1			Cohort 2			Cohorts 3 and 4			Cohort 5			Cohort 6			Cohort 7
Day	107 µg FimCH			50 µg FimCH 10 µg adjuvant			50 µg FimCH 20 µg adjuvant			50 µg FimCH 40 µg adjuvant			50 µg FimCH 40 µg adjuvant			107 µg FimCH 43 µg adjuvant
	N	GMT	95% CI	N	GMT	95% CI	N	GMT	95% CI	N	GMT	95% CI	N	GMT	95% CI	N	GMT	95% CI
1	5	-	-	8	-	-	16	-	-	8	-	-	16	-	-	14	4	3–6
30	5	10	1,76	8	14	4,47	16	8	4,19	7	20	4,93	15	20	6,65	14	15	7,33
60	4	65	6,764	8	63	16,240	13	124	47,329	7	456	139,1498	15	125	48,323	14	155	53,453
90	4	32	3,400	8	40	13,124	14	61	27,137	7	223	62,804	14	82	34,197	13	89	29,278
120	4	149	2,9253	7	125	26,607	14	435	180,1051	7	426	121,1505	14	389	228,662	13	322	153,678
180	3	22	5,97	7	51	13,202	14	95	46,197	7	188	36,991	13	141	72,275	13	105	39,280
210	3	235	9,5872	7	215	71,651	14	427	175,1043	7	1024	263,3993	13	473	247,904	13	706	294,1691
360	3	22	6,82	7	23	6,84	14	49	24,102	6	154	47,507	13	57	28,116	13	61	24,154

GMT – geometric mean titer; fold increase calculated using ½ the limit of quantitation of 3 µg/ml.

Table 5. Summary of local injection site symptom assessments reported in all subjects within 7 days of vaccination

		Cohort 1	Cohort 2	Cohorts 3 & 4	Cohort 5	Cohort 6	Cohort 7
Local InjectionSite Reactions		5 subjects (n = 17)	8 subjects (n = 30)	16 subjects (n = 61)	8 subjects (n = 29)	16 subjects (n = 58)	14 subjects (n = 54)
Pain/Burning	Mild and moderate	6 (35%)	11 (37%)	21 (34%)	15 (52%)	26 (45%)	36 (67%)
	Severe	0	0	0	0	2 (3%)	2 (4%)
Tenderness	Mild and moderate	7 (41%)	14 (47%)	23 (38%)	8 (28%)	44 (76%)	41 (76%)
	Severe	0	0	1 (2%)	0	1 (2%)	5 (9%)
Erythema/Redness	Mild and moderate	1 (6%)	3 (10%)	3 (5%)	6 (21%)	6 (10%)	13 (24%)
	Severe	0	0	0	1 (3%)	1 (2%)	1 (2%)
Induration/Swelling	Mild and moderate	0	1 (3%)	2 (3%)	7 (24%)	9 (16%)	20 (37%)
	Severe	0	0	0	0	1 (2%)	1 (2%)

Data (n) are from 249 vaccinations among 67 subjects. A continuum of events related to a single injection is defined as a single event, graded as the most severe occurrence.

Foxman B, Barlow R, D’Arcy H, Gillespie B, Sobel JD. Urinary tract infection: self-reported incidence and associated costs. Ann Epidemiol. 2000;10(8):509–15. doi:10.1016/s1047-2797(00)00072-7.

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