Evaluating the Safety and Protective Efficacy of a Single Dose of the Live Attenuated Tetravalent Dengue Vaccine TV005 to Protect Against Infection With rDEN3Δ30

Females Only: Currently pregnant, as determined by positive β-human choriogonadotropin (HCG) test, breast-feeding.

Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies.

Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the requirements of the study protocol.

Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in this protocol.

Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a subject participating in the trial or would render the subject unable to comply with the protocol.

Any significant alcohol or drug abuse in the past 12 months that has caused medical, occupational, or family problems, as indicated by subject history.

History of a severe allergic reaction or anaphylaxis.

Severe asthma (emergency room visit or hospitalization within the last 6 months).

HIV infection, by screening and confirmatory assays.

Hepatitis C virus (HCV) infection, by screening and confirmatory assays.

Hepatitis B virus (HBV) infection, by hepatitis B surface antigen (HBsAg) screening.

Any known immunodeficiency syndrome.

Current use of anticoagulant medications (this does not include anti-platelet medication such as aspirin or non-steroidal anti-inflammatory medications).

Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 28 days prior to or following vaccination. Immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg prednisone equivalent per day for greater than or equal to 14 days.

Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to vaccination or anticipated receipt of any vaccine during the 28 days following vaccination.

Asplenia.

Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination.

History or serologic evidence of previous dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis virus, West Nile virus). Subjects will also be screened for Zika virus if they have traveled in the past 18 months to areas of South \& Central America that have reported Zika-virus transmission (per Centers for Disease Control and Prevention \[CDC\] Zika travel information).

Previous receipt of a flavivirus vaccine (licensed or experimental).

Anticipated receipt of any investigational agent in the 28 days before or after vaccination.

Subject has definite plans to travel to a dengue endemic area during the study.

Refusal to allow storage of specimens for future research.

Anaphylaxis or angioedema following the TV005 administration.

Females Only: Currently pregnant, as determined by positive β- HCG test, breast-feeding.

Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies.

Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the requirements of the study protocol.

Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a subject participating in the trial or would render the subject unable to comply with the protocol.

Any significant alcohol or drug abuse in the past 12 months that has caused medical, occupational, or family problems, as indicated by subject history.

History of a severe allergic reaction or anaphylaxis.

Severe asthma (emergency room visit or hospitalization within the last 6 months).

HIV infection, by screening and confirmatory assays.

HCV infection, by screening and confirmatory assays.

HBV infection, by HBsAg screening.

Any known immunodeficiency syndrome.

Current use of anticoagulant medications (this does not include anti-platelet medication such as aspirin or non-steroidal anti-inflammatory medications).

Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 42 days prior to or following vaccination. Immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg prednisone equivalent per day for greater than or equal to 14 days.

Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to vaccination or anticipated receipt of any vaccine during the 28 days following vaccination.

Asplenia.

Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination.

Anticipated receipt of any other investigational agent in the 28 days before or after vaccination.

Subject has definite plans to travel to a dengue endemic area during the study.

Refusal to allow storage of specimens for future research.

The following criteria will be reviewed on Study Days 28 and 56 following each vaccination. If any become applicable during the study, the subject will not be included in per-protocol immunogenicity evaluations, as of the exclusionary visit. The subject will, however, be encouraged to remain in the study for safety evaluations until 6 months following the last vaccination (or challenge) received. The subject will have samples obtained at the protocol-defined time-points for immunogenicity and will be included in intention-to-treat immunogenicity analysis.

Use of any investigational drug or investigational vaccine other than the study vaccine during the 28-day period post-vaccination.

Chronic administration (greater than or equal to 14 days) of steroids (defined as prednisone equivalent of greater than or equal to 10 mg per day), immunosuppressants, or other immune-modifying drugs initiated during the 28-day period post-vaccination (topical and nasal steroids are allowed).

Receipt of a licensed vaccine during the 21-day period post vaccination.

Receipt of immunoglobulins and/or any blood products during the 28-day period post-vaccination.

Pregnancy -see clarifying language in the protocol. If the pregnancy is terminated spontaneously or by therapeutic abortion, immunogenicity assessments will be done on blood samples obtained after the termination of the pregnancy.

What this study is about