Vaccination of volunteers with low-dose, live-attenuated, dengue viruses leads to serotype-specific immunologic and virologic profiles

Janet C. Lindow, Anna P. Durbin, Stephen S. Whitehead, Kristen K. Pierce, Marya P. Carmolli, Beth D. Kirkpatrick

Research output: Contribution to journalArticle

Abstract

There are currently no vaccines or therapeutics to prevent dengue disease which ranges in severity from asymptomatic infections to life-threatening illness. The National Institute of Allergy and Infectious Diseases (NIAID) Division of Intramural Research has developed live, attenuated vaccines to each of the four dengue serotypes (DENV-1-DENV-4). Two doses (10. PFU and 1000. PFU) of three monovalent vaccines were tested in human clinical trials to compare safety and immunogenicity profiles. DEN4δ30 had been tested previously at multiple doses. The three dengue vaccine candidates tested (DEN1δ30, DEN2/4δ30, and DEN3δ30/31) were very infectious, each with a human infectious dose 50%. ≤. 10. PFU. Further, infectivity rates ranged from 90 to 100% regardless of dose, excepting DEN2/4δ30 which dropped from 100% at the 1000. PFU dose to 60% at the 10. PFU dose. Mean geometric peak antibody titers did not differ significantly between doses for DEN1δ30 (92 ± 19 vs. 214 ± 97, p=. 0.08); however, significant differences were observed between the 10. PFU and 1000. PFU doses for DEN2/4δ30, 19 ± 9 vs. 102 ± 25 (p=. 0.001), and DEN3δ30/31, 119 ± 135 vs. 50 ± 50 (p=. 0.046). No differences in the incidences of rash, neutropenia, or viremia were observed between doses for any vaccines, though the mean peak titer of viremia for DEN1δ30 was higher at the 1000. PFU dose (0.5 ± 0 vs. 1.1 ± 0.1, p=. 0.007). These data demonstrate that a target dose of 1000. PFU for inclusion of each dengue serotype into a tetravalent vaccine is likely to be safe and generate a balanced immune response for all serotypes.

Original languageEnglish (US)
Pages (from-to)3347-3352
Number of pages6
JournalVaccine
Volume31
Issue number33
DOIs
StatePublished - Jul 18 2013

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Keywords

  • Dengue vaccine
  • Dengue virus
  • HID
  • Low dose
  • Neutralizing antibodies
  • Viremia

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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