Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 215, Issue 3, Pages 351-358Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiw576
Keywords
Dengue vaccine; flavivirus; neutralizing antibody; live attenuated vaccine
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Funding
- Sanofi Pasteur, Lyon, France
- National Institute of Allergy and Infectious Diseases [01-AI125198-01]
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Sanofi Pasteur has developed a chimeric yellow fever-dengue, live-attenuated, tetravalent dengue vaccine (CYD-TDV) that is currently approved for use in several countries. In clinical trials, CYD-TDV was efficacious at reducing laboratory-confirmed cases of dengue disease. Efficacy varied by dengue virus (DENV) serotype and prevaccination dengue immune status. We compared the properties of antibodies in naive and DENV-exposed individuals who received CYD-TDV. We depleted specific populations of DENV-reactive antibodies from immune serum samples to estimate the contribution of serotype-cross-reactive and type-specific antibodies to neutralization. Subjects with no preexisting immunity to DENV developed neutralizing antibodies to all 4 serotypes of DENV. Further analysis demonstrated that DENV4 was mainly neutralized by type-specific antibodies whereas DENV1, DENV2, and DENV3 were mainly neutralized by serotype cross-reactive antibodies. When subjects with preexisting immunity to DENV were vaccinated, they developed higher levels of neutralizing antibodies than naive subjects who were vaccinated. In preimmune subjects, CYD-TDV boosted cross-reactive neutralizing antibodies while maintaining type-specific neutralizing antibodies acquired before vaccination. Our results demonstrate that the quality of neutralizing antibodies induced by CYD-TDV varies depending on DENV serotype and previous immune status. We discuss the implications of these results for understanding vaccine efficacy.
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