Safety and immunogenicity of a recombinant Staphylococcus aureusα-toxoid and a recombinant Panton-Valentine leukocidin subunit, in healthy adults

Figures & data

Figure 1. Flow diagram of subject enrollment and completion. Subjects were ineligible to receive second injection if they experienced a grade 3 adverse event or reactogenicity event after the first injection (all events determined probably unrelated to the first injection). For subjects in the 50 µg bivalent cohort (active vaccine, saline placebo, or alum placebo recipients) who received a second injection, the follow-up phone call and study completion occurred on Day 252.

Figure 2. Local or systemic reactogenicity (A) incidence and (B) severity during the first week following first vaccination in all treated subjects (n = 176).

Table 1. Summary of adverse events following first vaccination during follow-up in the safety population, No. (%). There was no significant difference in the incidence of overall AEs or AE's assessed to be treatment-related among the four main treatment groups, except subjects with ≥ 1 severe AE (p<0.01). p-values were calculated using a Wald test statistic for group in a generalized linear model for count outcomes

	rAT Doses^1	rLukS-PV Doses^1	rAT/rLukS-PV Doses^1	Placebo Doses^1
	N = 47	N = 49	N = 36	N = 44
Total AEs	102	105	79	112
Subjects with ≥1AE	37 (79)	40 (82)	28 (78)	36 (82)
Treatment-Related AEs^2	3	8	5	8
Subjects with ≥1 Treatment-Related AE^2	2 (4)	5 (10)	4 (11)	5 (11)
Total SAEs	0	1	3	1
Subjects with ≥1 SAE^3	0	1 (2)	3 (8)	1 (2)
Total Mild AEs	72	84	54	70
Subjects with ≥1 Mild AE	33 (70)	38 (78)	28 (78)	31 (71)
Total Moderate AEs	26	13	11	16
Subjects with ≥1 Moderate AE	12 (26)	10 (20)	8 (22)	14 (32)
Total Severe AEs	1	5	9	19
Subjects with ≥1 Severe AE	1 (2)	4 (8)	6 (17)	10 (23)

AE - adverse event; rAT - recombinant α-toxoid; rLukS - recombinant sub-unit of LukS of Panton-Valentine leukocidin; SAE - serious adverse event;

¹ Groups include all patients that received vaccination doses.

² Includes adverse events with unknown relationship.

³ SAEs were malignant astrocytoma (probably unrelated), hospitalization for non-cardiac chest pain (probably unrelated), hospitalization for alcoholism relapse (probably unrelated), hospitalization for pneumonia (probably unrelated), and thrombocytopenia secondary to idiopathic thrombocytopenic purpura (unknown relationship).

Figure 3. Antibody responses for (A) monovalent rAT; (B) bivalent rAT; (C) monovalent rLukS-PV; and (D) bivalent rLukS-PV formulations following first and second vaccination in the completer population. Visits are based on pre-defined windows for serology sample collection and not on the nominal visit. All out-of-window sample collections are excluded). After Day 84, the number of subjects who received the booster dose in the bivalent 50 µg cohorts was six.

Figure 4. a) Geometric mean titer of rAT neutralizing antibody b) Geometric mean titer of rLukS-PV neutralizing antibody following vaccination. Volunteers were vaccinated with 25 µg rLukS-PV, 50 µg rLukS-PV, 25µg rAT/rLukS-PV or 50 µg rAT/rLukS-PV. The 50 µg rAT/rLukS-PV cohort received a booster dose on day 84, and evaluation of neutralizing antibodies at day 112.

Figure 5. Scatterplot of total IgG levels and neutralizing activity at Day 84 post-vaccination against rAT for the following doses: 25 µg rAT, 50 µg rAT, 25 µg rAT/rLukS-PV or 50 µg rAT/rLukS-PV cohorts (5a), rLukS-PV for the 25 µg rLukS-PV, 50 rLukS-PV, 25 µg rAT/rLukS-PV or 50 µg rAT/rLukS-PV cohorts (5b). Scatterplot of total IgG levels and neutralizing activity against rAT (5c) and rLukS-PV (5d) at Day 112 following receipt of a booster dose of vaccine in patients who received the 50 µg rAT/rLukS-PV dose at baseline.