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

A randomized, controlled, double-blinded study was conducted to determine safety and immunogenicity of five live attenuated dengue vaccines produced by Aventis pasteur (AvP). The study was completed with 40 flavivirus non-immune volunteers: five recipients of each monovalent (dengue-l, dengue-2, dengue-3, or dengue-3) vaccine, ten recipients of tetravalent (dengue-l. dengue-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 occurred in volunteers followed for 6 months after vaccination. Five vaccine recipients developed fever ( T greater than or equal to 38.0 degreesC), including four tetravalent vaccinees between days 8 and 10 after vaccination. Dengue-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. Transient neutropenia (white blood cells < 4000/mm(3)) was noted after vaccination but not thrombocytopenia (platelets < 100000/mm(3)). All dengue-3, dengue-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 dengue-2, dengue-3, and dengue-4, and 60% of dengue-l vaccine recipients developed neutralizing and/or immunoglobulin M antibodies. AH tetravalent vaccine recipients were viremic with dengue-3 virus and developed neutralizing antibodies 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 infectivity and immunogenicity. Published by Elsevier Science Ltd.