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J Infect Dis. 2017 Feb 1;215(3):351-358. doi: 10.1093/infdis/jiw576.

Dissecting Antibodies Induced by a Chimeric Yellow Fever-Dengue, Live-Attenuated, Tetravalent Dengue Vaccine (CYD-TDV) in Naive and Dengue-Exposed Individuals.

Author information

1
Department of Microbiology and Immunology and.
2
Department of Epidemiology, Gillings School of Public Health, University of North Carolina, Chapel Hill.
3
Sanofi Pasteur, Orlando, Florida.
4
Sanofi Pasteur, Swiftwater, Pennsylvania.
5
Sanofi Pasteur, Lyon, France.

Abstract

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.

KEYWORDS:

Dengue vaccine; flavivirus; live attenuated vaccine.; neutralizing antibody

PMID:
27932620
PMCID:
PMC6392503
DOI:
10.1093/infdis/jiw576
[Indexed for MEDLINE]
Free PMC Article

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