The purpose of this research study is to test the protection of volunteers previously vaccinated with Tetravalent Dengue Virus (TDEN) Purified Inactivated Vaccine (PIV) with alum and boosted with TDEN live attenuated vaccine (LAV) formulation against a weakened form of an experimental dengue virus challenge. The Investigators will also include people that have not received the study vaccine. The Investigators are collecting information about how the vaccine protects against a dengue virus challenge as well as adding to knowledge about the safety of the challenge.
The purpose of this research study is to test the protection of volunteers previously vaccinated with Tetravalent Dengue Virus (TDEN) Purified Inactivated Vaccine (PIV) with alum and boosted with TDEN live attenuated vaccine (LAV) formulation against a weakened form of an experimental dengue virus challenge. The Investigators will also include people that have not received the study vaccine. The Investigators are collecting information about how the vaccine protects against a dengue virus challenge as well as adding to knowledge about the safety of the challenge. The information will help Investigators develop vaccines to protect people from dengue. Participation is voluntary. The duration of participation will last for 180 days (six months). After participants are exposed to the weakened dengue virus, the Investigators will follow them closely to measure their symptoms. Like the flu, participants might expect to have a headache, rash, body aches, fever and chills or they may experience no symptoms whatsoever. If a participant does develops symptoms, the Investigators will monitor him/her closely in a local hotel or a wing of our hospital to ensure safety and to treat symptoms if they occur. Participants will be compensated for their time.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
10
one subcutaneous injection of Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) at 0.5 mL of 6.5 x 10\^3 PFU/mL
University of Maryland, Baltimore, Center for Vaccine Development and Global Health
Baltimore, Maryland, United States
Number of Participants With Solicited Injection Site Adverse Events
Number of Participants with Solicited Injection Site Erythema - solicited injection site adverse event until 7 days post virus inoculation
Time frame: Days 2, 4, 5, 6, and 7
Number of Participants With Unsolicited Injection Site Adverse Events
Number of Participants with Injection site pain - unsolicited injection site adverse events until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Time frame: Days 2, 4, 5-16, 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)
Number of Participants With Solicited Systemic Adverse Events
Number of participants with solicited systemic adverse events until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Time frame: Days 2, 4-16, 19, 22, 25, and 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)
Number of Participants With Incidence of Abnormal Laboratory Measurements
Number of participants with incidence of abnormal laboratory measurements until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Time frame: Days 2, 4-16, 19, 22, 25, and 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)
Dengue-Related Illness Index
Scales: Clinical Symptoms: None=0, Mild=1, Moderate=2, Severe=3 (Min Score=0, Max=3) Laboratory Abnormalities: None=0, Mild=1, Moderate=2, Severe=3 based on modified FDA CBER laboratory scale (per protocol) (Min=0, Max=3) Symptoms (Clinical symptoms or Laboratory Abnormalities) duration: 1 point/day (Day 1-16) (Min=0, Max=16) Subscale A (Symptom Duration): 1 point/day (Day 1-16) across 10 Clinical/Laboratory findings (Min = 0, Max = 160) Subscale B (Symptom # per day): 1 point/ Clinical/Laboratory finding (n=10) per day across 16 days Min=0, Max=160 Subscale C (Max Severity Score/day): None=0, Mild=1, Moderate=2, Severe=3 across 16 days: Min=0, Max=48 Total Range in DII score (total scale) which equates to subscale (A + B + C)/3: Min=0, Max=122.7 https://doi.org/10.1016/s1473-3099(24)00100-2.
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Time frame: Days 1-16
Number of Participants With Unsolicited Systemic Adverse Events
Number of participants with unsolicited systemic adverse events until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Time frame: Days 2, 4-16, 19, 22, 25, and 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)
Number of Participants With Short-Term SAEs
Number of participants with SAEs until 28 days post virus inoculation or 7 days post hospitalization, whichever is later
Time frame: Days 2, 4-16, 19, 22, 25, and 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)
Number of Participants With Long-Term SAEs
Number of participants with SAEs until 6 months post virus inoculation
Time frame: Days 2-180
Number of Participants With Persistent Fever
Number of participants with persistent fever defined as greater than or equal to 38°C (100.4° F) measured at least 2 times at least 4 hours apart
Time frame: Days 2-28