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

N Kanesa-Thasan, W Sun, G Kim-Ahn, S Van Albert… - Vaccine, 2001 - Elsevier
N Kanesa-Thasan, W Sun, G Kim-Ahn, S Van Albert, JR Putnak, A King, B Raengsakulsrach…
Vaccine, 2001Elsevier
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-1, dengue-2, dengue-3, or dengue-4) vaccine, ten recipients of
tetravalent (dengue-1, dengue-2, dengue-3, and dengue-4) vaccine, and ten recipients of
vaccine vehicle alone. All vaccines were administered in a single subcutaneous dose …
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-1, dengue-2, dengue-3, or dengue-4) vaccine, ten recipients of tetravalent (dengue-1, dengue-2, dengue-3, and dengue-4) vaccine, and ten recipients of vaccine vehicle alone. All vaccines were administered in a single subcutaneous dose (range, 3.6–4.4 log10 plaque forming units). No serious adverse reactions occurred in volunteers followed for 6 months after vaccination. Five vaccine recipients developed fever (T≥38.0°C), including four tetravalent vaccinees between days 8 and 10 after vaccination. Dengue-1, 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/mm3) was noted after vaccination but not thrombocytopenia (platelets<100 000/mm3). All dengue-3, dengue-4, and tetravalent vaccine recipients were viremic between days 7 and 12 but viremia was rarely detected in dengue-1 or dengue-2 vaccinees. All dengue-2, dengue-3, and dengue-4, and 60% of dengue-1 vaccine recipients developed neutralizing and/or immunoglobulin M antibodies. All 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.
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