This study will evaluate 3 doses of a new vaccine for rotavirus infection in healthy adult volunteers to determine if it is safe and if the immune systems of healthy adults respond to this vaccine.
The trial will be a double-blinded, randomized, placebo-controlled dose-escalation study in which three dose-levels of vaccine will be tested in adults. Cohorts of 16 individuals (12 vaccine recipients and 4 placebo recipients) per dose level will receive three intramuscular injections four weeks apart. The three dose levels of vaccine to test will be 10 microgram (μg), 30 μg and 60 μg.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
48
P2-VP8 subunit rotavirus vaccine was made by inserting a codon optimized synthetic gene for the VP8 region of rotavirus VP4 fused to the P2 T-cell epitope of tetanus toxin into the Pj411 proprietary cloning vector developed by DNA 2.0, Menlo Park, CA. The vector carries a kanamycin resistance gene as a selection marker. The vector was transfected into the BL21 strain of E. coli. The fusion protein was purified from Isopropyl β-D-1-thiogalactopyranoside (IPTG)-induced and physically lysed cultures using standard column chromatographic techniques employing Q-Sepharose and Butyl 650 as resins in addition to ultrafiltration and diafiltration.
Sodium Chloride 0.9%, USP for Injection was used to dilute the active P2-VP8 vaccine to final dosing concentration and was used for the Placebo for the study.
Center for Immunization Research
Baltimore, Maryland, United States
Maximum Severity of Adverse Events After Any Vaccination
Adverse events were collected through 28 days following the final study injection and were graded for severity. Unsolicited adverse events were also assessed for relationship to vaccine. A final follow-up contact was attempted 6 months following the final study injection to inquire about new chronic health conditions, serious health events, and hospitalizations.
Time frame: 6 months after final vaccination (224 days)
Maximum Local or Systemic Reactogenicity After Any Vaccination
For all cohorts, local and systemic reactogenicity data for all vaccinations were collected by subjects via diary card up to 7 days post each vaccination. Solicited systemic reactogenicity events included headache, muscle pain, fever, nausea, vomiting, fatigue, joint aches, and chills. Solicited local systemic reactogenicity events included injection site pain, tenderness, redness, swelling, itching, and local lymphadenopathy.
Time frame: 7 days after each vaccination (Day 7, 35, 63)
Maximum Local or Systemic Reactogenicity After the First Vaccination
For all cohorts, local and systemic reactogenicity data for all vaccinations were collected by subjects via diary card up to 7 days post each vaccination. Solicited systemic reactogenicity events included headache, muscle pain, fever, nausea, vomiting, fatigue, joint aches, and chills. Solicited local systemic reactogenicity events included injection site pain, tenderness, redness, swelling, itching, and local lymphadenopathy.
Time frame: 7 days post Vaccination #1 on Day 0
Maximum Local or Systemic Reactogenicity After the Second Vaccination
For all cohorts, local and systemic reactogenicity data for all vaccinations were collected by subjects via diary card up to 7 days post each vaccination. Solicited systemic reactogenicity events included headache, muscle pain, fever, nausea, vomiting, fatigue, joint aches, and chills. Solicited local systemic reactogenicity events included injection site pain, tenderness, redness, swelling, itching, and local lymphadenopathy.
Time frame: 7 days post Vaccination #2 on Day 35
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Maximum Local or Systemic Reactogenicity After the Third Vaccination
For all cohorts, local and systemic reactogenicity data for all vaccinations were collected by subjects via diary card up to 7 days post each vaccination. Solicited systemic reactogenicity events included headache, muscle pain, fever, nausea, vomiting, fatigue, joint aches, and chills. Solicited local systemic reactogenicity events included injection site pain, tenderness, redness, swelling, itching, and local lymphadenopathy.
Time frame: 7 days post Vaccination #3 on Day 56
Number and Percentage of Subjects With Anti-P2-VP8 Immunoglobulin G (IgG) and Immunoglobulin A (IgA) Seroresponses
Seroresponse was defined as as a four-fold increase in antibody titers between baseline and 4-weeks post-third injection.
Time frame: 4 weeks post 3rd immunization (84 days)
Geometric Mean Titer (GMT) of Anti-P2-VP8 Immunoglobulin G (IgG)
Measured from sera taken on Days 0, 28, 56 and 84 (before the first injection and 4 weeks after each injection).
Time frame: Days 0, 28, 56 and 84 (before the first injection and 4 weeks after each injection)
Geometric Mean Titer (GMT) of Anti-P2-VP8 Immunoglobulin A (IgA)
Measured from sera taken on Days 0, 28, 56 and 84 (before the first injection and 4 weeks after each injection).
Time frame: Days 0, 28, 56 and 84 (before the first injection and 4 weeks after each injection)
Number and Percentage of Subjects With Serum Neutralizing Antibody Seroresponse, by Rotavirus Strain
Seroresponse was defined as as a four-fold increase in antibody titers between baseline and 4-weeks post-third injection.
Time frame: 4 weeks post 3rd immunization (84 days)