Analyzing the Human Serum Antibody Responses to a Live Attenuated Tetravalent Dengue Vaccine Candidate

Jesica A. Swanstrom, Sandra Henein, Jessica Plante, Boyd L. Yount, Douglas G. Widman, Emily N. Gallichotte, Hansi J. Dean, Jorge E. Osorio, Charalambos D. Partidos, Aravinda M. De Silva, Ralph S. Baric

Research output: Contribution to journalArticle

Abstract

Background Dengue virus serotypes 1-4 (DENV-1-4) are the most common vector-borne viral pathogens of humans and the etiological agents of dengue fever and dengue hemorrhagic syndrome. A live-attenuated tetravalent dengue vaccine (TDV) developed by Takeda Vaccines has recently progressed to phase 3 safety and efficacy evaluation. Methods We analyzed the qualitative features of the neutralizing antibody (nAb) response induced in naive and DENV-immune individuals after TDV administration. Using DENV-specific human monoclonal antibodies (mAbs) and recombinant DENV displaying different serotype-specific Ab epitopes, we mapped the specificity of TDV-induced nAbs against DENV-1-3. Results Nearly all subjects had high levels of DENV-2-specific nAbs directed to epitopes centered on domain III of the envelope protein. In some individuals, the vaccine induced nAbs that tracked with a DENV-1-specific neutralizing epitope centered on domain I of the envelope protein. The vaccine induced binding Abs directed to a DENV-3 type-specific neutralizing epitope, but findings of mapping of DENV-3 type-specific nAbs were inconclusive. Conclusion Here we provide qualitative measures of the magnitude and epitope specificity of the nAb responses to TDV. This information will be useful for understanding the performance of TDV in clinical trials and for identifying correlates of protective immunity.

LanguageEnglish (US)
Pages1932-1941
Number of pages10
JournalJournal of Infectious Diseases
Volume217
Issue number12
DOIs
StatePublished - May 25 2018
Externally publishedYes

Fingerprint

Dengue Vaccines
Antibody Formation
Epitopes
Serum
Vaccines
Neutralizing Antibodies
Severe Dengue
Epitope Mapping
Dengue Virus
Dengue
Immunity
Proteins
Monoclonal Antibodies
Clinical Trials
Safety

Keywords

  • antibody
  • dengue
  • Flavivirus
  • immunity
  • live-attenuated vaccine
  • vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Swanstrom, J. A., Henein, S., Plante, J., Yount, B. L., Widman, D. G., Gallichotte, E. N., ... Baric, R. S. (2018). Analyzing the Human Serum Antibody Responses to a Live Attenuated Tetravalent Dengue Vaccine Candidate. Journal of Infectious Diseases, 217(12), 1932-1941. https://doi.org/10.1093/infdis/jiy063

Analyzing the Human Serum Antibody Responses to a Live Attenuated Tetravalent Dengue Vaccine Candidate. / Swanstrom, Jesica A.; Henein, Sandra; Plante, Jessica; Yount, Boyd L.; Widman, Douglas G.; Gallichotte, Emily N.; Dean, Hansi J.; Osorio, Jorge E.; Partidos, Charalambos D.; De Silva, Aravinda M.; Baric, Ralph S.

In: Journal of Infectious Diseases, Vol. 217, No. 12, 25.05.2018, p. 1932-1941.

Research output: Contribution to journalArticle

Swanstrom, JA, Henein, S, Plante, J, Yount, BL, Widman, DG, Gallichotte, EN, Dean, HJ, Osorio, JE, Partidos, CD, De Silva, AM & Baric, RS 2018, 'Analyzing the Human Serum Antibody Responses to a Live Attenuated Tetravalent Dengue Vaccine Candidate' Journal of Infectious Diseases, vol. 217, no. 12, pp. 1932-1941. https://doi.org/10.1093/infdis/jiy063
Swanstrom, Jesica A. ; Henein, Sandra ; Plante, Jessica ; Yount, Boyd L. ; Widman, Douglas G. ; Gallichotte, Emily N. ; Dean, Hansi J. ; Osorio, Jorge E. ; Partidos, Charalambos D. ; De Silva, Aravinda M. ; Baric, Ralph S. / Analyzing the Human Serum Antibody Responses to a Live Attenuated Tetravalent Dengue Vaccine Candidate. In: Journal of Infectious Diseases. 2018 ; Vol. 217, No. 12. pp. 1932-1941.
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