Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers

A randomized, controlled, double-blinded study was conducted to determine s afety and immunogenicity of five live attenuated dengue vaccines produced b y Aventis pasteur (AvP). The study was completed with 40 flavivirus non-imm une volunteers: five recipients of each monovalent (dengue-l, dengue-2, den gue-3, or dengue-3) vaccine, ten recipients of tetravalent (dengue-l. dengu e-2, dengue-3, and dengue-3) vaccine, and ten recipients of vaccine vehicle alone. All vaccines were administered in a single subcutaneous dose (range , 3.6-4.4 log(10) plaque forming units). No serious adverse reactions occur red in volunteers followed for 6 months after vaccination. Five vaccine rec ipients developed fever ( T greater than or equal to 38.0 degreesC), includ ing four tetravalent vaccinees between days 8 and 10 after vaccination. Den gue-l, dengue-2, dengue-3, or dengue-4 vaccine recipients reported similar frequency of mild symptoms of headache, malaise, and eye pain. Tetravalent vaccinees noted more moderate symptoms with onset from study days 8-11 and developed maculopapular rashes distributed over trunk and extremities. Tran sient neutropenia (white blood cells < 4000/mm(3)) was noted after vaccinat ion but not thrombocytopenia (platelets < 100000/mm(3)). All dengue-3, deng ue-4, and tetravalent vaccine recipients were viremic between days 7 and 12 but viremia was rarely detected in dengue-l or dengue-2 vaccinees. All den gue-2, dengue-3, and dengue-4, and 60% of dengue-l vaccine recipients devel oped neutralizing and/or immunoglobulin M antibodies. AH tetravalent vaccin e recipients were viremic with dengue-3 virus and developed neutralizing an tibodies to dengue-3 virus. Seven volunteers also had multivalent antibody responses, yet the highest antibody titers were against dengue-3 virus. The AvP live attenuated dengue virus vaccines are safe and tolerable in humans . The live attenuated tetravalent dengue vaccine was most reactogenic, and preferential replication of dengue-3 virus may have affected its infectivit y and immunogenicity. Published by Elsevier Science Ltd.