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-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 log(10) plaque forming units). No serious adverse reactions occurred in volunteers followed for 6 months after vaccination. Five vaccine recipients developed fever (T > or = 38.0 degrees 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.
Kanesa-thasan
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N
Walter Reed Army Institute of Research, Washington, DC, USA. niranjan.kanesa-thasan@na.amedd.army.mil
Sun
W
W
Kim-Ahn
G
G
Van Albert
S
S
Putnak
J R
JR
King
A
A
Raengsakulsrach
B
B
Christ-Schmidt
H
H
Gilson
K
K
Zahradnik
J M
JM
Vaughn
D W
DW
Innis
B L
BL
Saluzzo
J F
JF
Hoke
C H
CH
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D003715:Dengue / Q000276:immunology / Q000517:prevention & control; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D012449:Safety; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology*; D014766:Viremia / Q000209:etiology
D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines