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This was a randomized, double-blind, ascending dose study conducted at a single clinical research center.
Healthy adult subjects aged 18 to 55 years were assigned to 3 ascending dose cohorts of Typhax (0.5, 2.5 or 10 mcg Vi antigen). Groups of 15 subjects in each dose cohort were randomized to receive Typhax, Typhim Vi (25 mcg Vi antigen) or placebo (saline) in a ratio of 3:1:1, respectively. Typhax and placebo (saline) was administered as two dose regimen (Days 0 and 28), and Typhim Vi was given as a single dose (Day 0) with matching placebo on Day 28. All doses were administered by a unblinded third-party as 0.5 mL by intramuscular (IM) injection. Safety and reactogenicity endpoints was assessed at 14 and 28 days after the first Typhax vaccination and 14 days after the second vaccination. Immunogenicity was assessed using an enzyme-linked immunosorbent assay (ELISA) to measure anti-Vi antibody serum titers on days 0, 14, 28, 42 and 180. A positive immune response (seroconversion) by ELISA is defined as at least a 4-fold increase over baseline in the Vi-specific ELISA.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Typhax 0.5 mcg | Experimental | Vaccine was administered IM on Days 0 and 28 (n=9). |
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| Typhax 2.5 mcg | Experimental | Vaccine was administered IM on Days 0 and 28 (n=9). |
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| Typhax 10 mcg | Experimental | Vaccine was administered IM on Days 0 and 28 (n=9). |
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| Typhim Vi 25 mcg | Active Comparator | Vaccine was administered IM Day 0 (n=9) followed by placebo control on Day 28 |
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| Placebo (saline) | Placebo Comparator | Placebo control was administered IM Days 0 and 28 ( n=9) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Typhax (investigational typhoid fever candidate vaccine) | Biological |
| ||
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants reporting solicited injection site and systemic events and unsolicited adverse events following vaccination with Typhax | Solicited Injection Site reactions: Pain, Tenderness, Erythema, Induration; Solicited Systemic Reactions Fever, Headache, Joint Pain, Joint Swelling, Fatigue, Myalgia, Nausea, Vomiting, Diarrhea | Days 0 up to Day 56 (= 28 Days post second vaccination) |
| Number of participants reporting adverse events following vaccination with Typhax | Adverse events are assessed at study visits by PI for seriousness, relationship to investigational product , severity and other possible etiologies | Days 0 up to Day 210 |
| Anti-Vi IgG antibody seroconversion and geometric mean antibody titers | The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 14 after vaccination. | Day 0 - Day 14 |
| Anti-Vi IgG antibody seroconversion and geometric mean antibody titers | The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 28 after vaccination. | Day 0 - Day 28 |
| Anti-Vi IgG antibody seroconversion and geometric mean antibody titers | The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 42. | Day 0 - Day 42 |
| Anti-Vi IgG antibody seroconversion and geometric mean antibody titers | The immunogenicity will be measured by ELISA for anti-Vi percent seroconversion and GMTs before and at day 180. |
| Measure | Description | Time Frame |
|---|---|---|
| Vi-specific B-cell ELISPOT responses | Immunogenicity was evaluated by comparing the number of Vi-specific B-cells by ELISPOT in PBMC samples | Days 0 through 38 |
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Inclusion Criteria:
Exclusion Criteria:
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31905228 | Derived | Cartee RT, Thanawastien A, Griffin Iv TJ, Mekalanos JJ, Bart S, Killeen KP. A phase 1 randomized safety, reactogenicity, and immunogenicity study of Typhax: A novel protein capsular matrix vaccine candidate for the prevention of typhoid fever. PLoS Negl Trop Dis. 2020 Jan 6;14(1):e0007912. doi: 10.1371/journal.pntd.0007912. eCollection 2020 Jan. |
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| ID | Term |
|---|---|
| D014435 | Typhoid Fever |
| ID | Term |
|---|---|
| D012480 | Salmonella Infections |
| D004756 | Enterobacteriaceae Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
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Randomized, Ascending Dose
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Study vaccine will be administered by an unblinded staff member at the clinic
| Placebo |
| Biological |
Placebo is administered to the control group on Day 0 and 28 |
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| Active Comparator Typhim Vi | Biological | A single dose of commercial typhoid fever vaccine Typhim Vi is administered on Day 0, followed by placebo control on Day 28 |
|
| Day 0 - Day 180. |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |