The primary objective of this study is to evaluate the antibody response to the cholera vaccine, Vaxchora®, in healthy subjects. Investigators also seek to evaluate additional markers of the adaptive immune response including plasmablasts, activated B cells, memory B cells, and T cell responses in healthy subjects receiving cholera vaccine, produce monoclonal antibodies against cholera, and evaluate the safety and reactogenicity in healthy subjects receiving cholera vaccine.
Vibrio cholerae causes an acute diarrheal disease responsible for more than 100,000 deaths and affects an estimated 3 to 5 million people annually. Recent epidemics in Haiti and Africa illustrate the continued reach of this pathogen. Across the globe, one billion people lack access to safe drinking water and are vulnerable to cholera. The increasing disease burden, and emergence of more virulent strains, suggest that more aggressive approaches to preventing cholera are needed. This includes renewed efforts to understand the mechanism of protective immunity against cholera and to improve the protective efficacy of current cholera vaccines. Vaxchora is a live attenuated cholera vaccine that protects against some cholera strains. It has been approved by the FDA since June 2016. Since October, 2016, this vaccine has been recommended for certain travelers 18 through 64 years of age going to cholera-affected areas. The purpose of this study is to look at the immune responses to the FDA approved cholera vaccine (Vaxchora®). This study aims to enroll 50 participants who will receive the Vaxchora live cholera vaccine, of whom 30 will undergo two procedures for small intestinal biopsies: one at screening and the other post vaccination (25 participants at Day 29 and 5 participants at day 90) by an upper endoscopy biopsy (EGD).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
34
Vaxchora is a live attenuated cholera vaccine that provides immunity against V. cholerae serogroup O1. Participants will receive one single oral dose of 100 mL.
The Hope Clinic of Emory University
Atlanta, Georgia, United States
Level of Antibody Titers in Serum
Antibody response is evaluated as the level of antibody titers in serum. Higher vibriocidal antibody titers indicate greater protection against cholera.
Time frame: Day 1 (pre-vaccination), Day 29
Plasmablast Levels
Plasmablasts are collected via blood draw and isolated and assessed for counts by the study team.
Time frame: Day 1 (pre-vaccination), Day 8, Day 29
Activated B Cell Levels
Activated B cells are collected via blood draw and isolated and assessed for counts by the study team.
Time frame: Day 1 (pre-vaccination), Day 8, Day 29
Memory B Cell Levels
Memory B cells are collected via blood draw and isolated and assessed for counts by the study team. The level of memory B cells is evaluated as the percentage of antigen specific immunoglobulin (Ig) secreting cells divided by the total Ig secreting cells.
Time frame: Day 1 (pre-vaccination), Day 29
Number of Monoclonal Antibodies Produced Per Participant
The number of antigen-specific monoclonal antibodies (mAbs) was assessed in a subset of participants on Day 8 post-vaccination. Peripheral blood mononuclear cells (PBMCs) were isolated, and antigen-specific plasmablasts were single-cell sorted using fluorescently labeled V. cholerae antigens (e.g., CTB and LPS). Paired immunoglobulin heavy and light chain variable regions were amplified by RT-PCR, cloned into expression vectors, and expressed in mammalian cells. The number of unique antigen-specific monoclonal antibodies was determined by binding assays (e.g., ELISA).
Time frame: Day 8
Number of Cholera Toxin B (CTB) Specific Monoclonals and Lipopolysaccharide (LPS) Specific Monoclonal Antibodies Per Participant
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The monoclonal antibodies obtained were characterized as cholera toxin B (CTB) specific monoclonals and lipopolysaccharide (LPS) specific monoclonals. The characterization of monoclonal antibodies against V. cholerae is assessed in a subset of participants.
Time frame: Day 8
Number of Adverse Events
The number of solicited and unsolicited adverse events were collected.
Time frame: Up to Day 8, Up to Day 29
Number of Serious Adverse Events
The number of serious adverse events were collected during the duration of the study.
Time frame: Up to Day 365