The purpose of this study is to assess the safety of increasing doses of a potential vaccine against Campylobacter with and without Alhydrogel®, an aluminum hydroxide adjuvant. This study will also assess immune responses induced by the vaccine.
This is an open-label, dose-escalating study in which a total of 48 healthy volunteers will receive 2 vaccinations (one on Day 0 and one on Day 28 ± 2 days). There are 3 cohorts (dose levels) with 2 groups of 8 volunteers in each cohort. A cohort will be administered one of 3 intramuscular (IM) doses at 2 μg, 5 μg, or 10 μg of Capsule-Conjugate Campylobacter Vaccine (CJCV1) with or without Alhydrogel®, aluminum hydroxide adjuvant (alum) at 125 μg. An interval no less than 1 week will separate the last dose of a volunteer group from the first dose of the next volunteer group (receiving different CJCV1 doses). Blood specimens will be collected at intervals to examine systemic and mucosal antigen-specific immune responses. Vaccine safety will be actively monitored during vaccination and for 28 days (± 2 days) following the second vaccination and complete the study with a telephone follow-up approximately 6 months (± 1 month) after the first vaccination. The total duration of participation in this study is up to 270 days (including screening).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
48
The capsule of Campylobacter jejuni strain 81-176 (CPS81-176) conjugated to the mutated diphtheria toxin cross-reacting material 197 (CRM197) (lyophilized CPS-CRM197 conjugate) (CJCV1)
Walter Reed Army Institute of Research
Silver Spring, Maryland, United States
Safety: Presence of Related/Not Related Local and/or Systemic Reactogenicity (Adverse Events)
Vaccine safety will be assessed by evaluating post-vaccination local and systemic reactions through targeted physical exams, symptom surveys, and other adverse event (AE) monitoring. All subjects will be observed in the clinic for at least 30 minutes after receipt of the investigational product. Approximately 48 hours after vaccination, subjects will return to the Clinical Trials Center for observation and reporting of any local and/or systemic AEs. Seven days after vaccine administration, subjects will return to the Clinical Trials Center to review their memory aids with study personnel and to report any AEs. In addition to planned visits, if a subject experiences any unanticipated AE, the subject will be seen by one of the study investigators. All AEs will be coded for onset date, duration, severity, and potential relationship to the investigational product.
Time frame: up to 7 days
Frequency (%) of Vaccine-specific Immune Responses by Assay and Antigen Using Enzyme-linked Immunosorbent Assay (ELISA)
Primary immunologic parameters, serum samples were assessed for the antibody titers against Campylobacter jejuni conjugate vaccine1 (CJCV1) using ELISA (enzyme-linked immunosorbent assay) based methods. Antibody-secreting cell(s) (ASCs): \>0.5 per 10(6) Peripheral blood mononuclear cell (PBMCs) in the baseline sample. When the number of baseline ASCs is less than 0.5 per 10(6) PBMCs, a subject was considered a responder if the post-vaccination value was greater than 1.0 per 10(6) PBMCs. ((6) is superscript). 1. = Seroconversion was defined as \>4fold increase in endpoint titer between pre- and post-vaccine samples and a post-vaccine reciprocal titer \>10. 2. = Response is defined as a \>2fold increase over the baseline value of ASC per 10(6) PBMCs, when the number of ASCs is \>0.5 per 10(6) PBMCs in the baseline sample. When the number of baseline ASCs is less than 0.5 per 10(6) PBMCs, a subject was considered a responder if the post-vaccine value was greater than 1.0 per 10(6) PBMCs.
Time frame: Study Days 0-56
Vaccine-specific Geometric Mean Titers (GMT) of Anti-CPS IgG Antibody-secreting Cells
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Anti-CPS IgG ASC Responses - GMTs with 95% CI. A positive immunoglobulin A (IgA)-ASC response will be defined as a \> twofold increase over the baseline value of the ASCs per 10\^6 peripheral blood mononuclear cells (PBMCs). A subject will be considered a responder if the post-vaccination value is greater than 2.0 per 10\^6 PBMCs. Blood samples will also be utilized to explore in vitro production of interferon (IFN)-(gamma).
Time frame: Study Days 0-56
Vaccine-specific Anti-CRM^197 IgA Antibody-secreting Cell (ASC) Responses
Anti-CRM\^197 IgG ASC Responses - GMTs with 95% CI. A positive immunoglobulin A (IgA)-ASC response will be defined as a \> twofold increase over the baseline value of the ASCs per 10\^6 peripheral blood mononuclear cells (PBMCs). A subject will be considered a responder if the post-vaccination value is greater than 2.0 per 10\^6 PBMCs. Blood samples will also be utilized to explore in vitro production of interferon (IFN)-(gamma).
Time frame: Study Days 0-56
Interferon Titers Among All Cohorts
CRM197-specific interferon-y (IFNy) responses measured from PBMC on day0, 28 and 56
Time frame: Day 0, 28 and 56