Clinical trial NCT00094718: Safety of and Immune Response to a West Nile Virus Vaccine (WN/DEN4-3'delta30) in Healthy Adults
Official title: Phase 1 Study of the Safety and Immunogenicity of West Nile/Dengue-4 3'delta30 Chimeric Virus Vaccine (WN/DEN4-3'delta30), a Live Attenuated Vaccine for West Nile Encephalitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: West Nile Fever Encephalitis
Keywords: Chimeric Virus Vaccine
West Nile Virus
Dengue Virus
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Johns Hopkins Bloomberg School of Public Health
First posted: 2004-10-22
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: West Nile (WN) virus infection is an emerging disease; WN infection may lead to paralysis, coma, and death. The purpose of this study is to test the safety of and immune response to a WN vaccine in healthy adults. The vaccine is based on a live attenuated vaccine developed against dengue virus.

Detailed description: WN is widely distributed in Africa and Europe, where it is usually associated with mild illness. In the United States, WN is considered a public health threat because severe illness caused by WN infection has caused paralysis, coma, and death, especially in the elderly. This study will evaluate the safety and immunogenicity of a live attenuated chimeric virus, WN/DEN4-3'delta30, which is derived from the DEN4 dengue virus and wild-type WN serotypes.

This study will last 180 days. Participants in Cohort 1 will be randomly assigned to receive the lowest dose of WN/DEN4-3'delta30 or placebo at study entry. Cohort 2 will begin only after safety review of all participants in Cohort 1. Participants in Cohort 2 will receive a higher dose of WN/DEN4-3'delta30 or placebo. Cohort 3 will begin only after safety review of all participants in Cohort 2. Participants in Cohort 3 will receive the highest dose of WN/DEN4-3'delta30 or placebo. Immediately after receiving their injections, participants will be observed for 30 minutes for immediate adverse reactions.

After vaccination, participants will be asked to monitor their temperatures every day for 16 days and on Day 19. Study visits will occur every other day after vaccination until Day 16, followed by 5 additional visits at selected days through Day 180. Blood collection and a targeted physical exam will occur at each study visit. Some participants will be asked to undergo a skin biopsy or additional blood collection at selected visits.

Eligibility criteria: Inclusion Criteria:

* Willing to be followed for the duration of the study
* Willing to use acceptable methods of contraception
* Good general health

Exclusion Criteria:

* Clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease
* Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the ability of the volunteer to understand and cooperate with the study
* Hematologic disease
* History of migraine headaches
* History of encephalitis
* Alcohol or drug abuse within 12 months prior to study entry
* History of severe allergic reaction or anaphylaxis
* Emergency room visit or hospitalization for severe asthma within 6 months prior to study entry
* HIV-1 infected
* Hepatitis C virus infected
* Hepatitis B surface antigen positive
* Known immunodeficiency syndrome
* Use of corticosteroids or immunosuppressive drugs within 30 days of study entry. Participants who have used topical or nasal corticosteroids are not excluded.
* Live vaccine within 4 weeks prior to study entry
* Killed vaccine within 2 weeks prior to study entry
* Blood products within 6 months prior to study entry
* Participation in another investigational vaccine or drug trial within 60 days of starting this study, or while participating in this study
* Previously received a licensed or experimental yellow fever, tick-borne encephalitis, or dengue vaccine
* Surgical removal of spleen
* History of West Nile encephalitis
* History of dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus)
* Other condition that, in the opinion of the investigator, would affect the participant's participation in the study
* Pregnancy or breastfeeding

Primary outcomes:
measure: Frequency of vaccine-related adverse effects, graded by severity, for each dose
timeFrame: Throughout study
measure: Immunogenicity of vaccine against WN virus
timeFrame: Throughout study
Secondary outcomes:
measure: To assess the durability of the antibody response
timeFrame: At Day 180
measure: To assess the frequency, quantity, and duration of viremia in each dose cohort studied
timeFrame: Throughout study
measure: To assess the immunogenicity of the WN/DEN4-3'delta30 vaccine against WN wild-type virus
timeFrame: Throughout study
measure: To compare the T cell medicated immune response against West Nile virus of those volunteers infected with the WN/DEN4-3'delta30 vaccine virus with that of uninfected volunteers and placebo recipients
timeFrame: At study completion
measure: To evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy
timeFrame: Throughout study
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins School of Public Health
state: Maryland
city: Nashville
country: United States
facility: Vanderbilt University School of Medicine
state: Tennessee
Study officials:
affiliation: Center for Immunization Research, Johns Hopkins School of Public Health
name: Anna Durbin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chang GJ, Kuno G, Purdy DE, Davis BS. Recent advancement in flavivirus vaccine development. Expert Rev Vaccines. 2004 Apr;3(2):199-220. doi: 10.1586/14760584.3.2.199.
citation: Lai CJ, Monath TP. Chimeric flaviviruses: novel vaccines against dengue fever, tick-borne encephalitis, and Japanese encephalitis. Adv Virus Res. 2003;61:469-509. doi: 10.1016/s0065-3527(03)61013-4.
citation: Monath TP, McCarthy K, Bedford P, Johnson CT, Nichols R, Yoksan S, Marchesani R, Knauber M, Wells KH, Arroyo J, Guirakhoo F. Clinical proof of principle for ChimeriVax: recombinant live, attenuated vaccines against flavivirus infections. Vaccine. 2002 Jan 15;20(7-8):1004-18. doi: 10.1016/s0264-410x(01)00457-1.
citation: Pletnev AG, Claire MS, Elkins R, Speicher J, Murphy BR, Chanock RM. Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus. Virology. 2003 Sep 15;314(1):190-5. doi: 10.1016/s0042-6822(03)00450-1.
citation: Pugachev KV, Guirakhoo F, Trent DW, Monath TP. Traditional and novel approaches to flavivirus vaccines. Int J Parasitol. 2003 May;33(5-6):567-82. doi: 10.1016/s0020-7519(03)00063-8.