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

Abstract

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.

• Authors: N Kanesa-thasan, W Sun, G Kim-Ahn, S Van Albert, J R Putnak, A King, B Raengsakulsrach, H Christ-Schmidt, K Gilson, J M Zahradnik, D W Vaughn, B L Innis, J F Saluzzo, C H Hoke Jr
• Journal: Vaccine (Vaccine) Vol. 19 Issue 23-24 Pg. 3179-88 (Apr 30 2001) ISSN: 0264-410X [Print] Netherlands
• PMID: 11312014 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Viral
• Vaccines, Attenuated
• Viral Vaccines

Topics

• Adolescent
• Adult
• Antibodies, Viral (blood)
• Dengue (immunology, prevention & control)
• Dengue Virus (classification, immunology)
• Double-Blind Method
• Female
• Humans
• Leukocyte Count
• Male
• Middle Aged
• Platelet Count
• Safety
• Vaccines, Attenuated (adverse effects, immunology, pharmacology)
• Viral Vaccines (adverse effects, immunology, pharmacology)
• Viremia (etiology)