Investigating the efficacy of monovalent and tetravalent dengue vaccine formulations against DENV-4 challenge in AG129 mice

Jeremy Fuchs, Haiyan Chu, Peter O'Day, Richard Pyles, Nigel Bourne, Subash C. Das, Gregg Milligan, Alan Barrett, Charalambos D. Partidos, Jorge E. Osorio

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Dengue (DEN) is the most important mosquito-borne viral disease, with a major impact on global health and economics, caused by four serologically and distinct viruses termed DENV-1 to DENV-4. Currently, there is no licensed vaccine to prevent DEN. We have developed a live attenuated tetravalent DENV vaccine candidate (TDV) (formally known as DENVax) that has shown promise in preclinical and clinical studies and elicits neutralizing antibody responses to all four DENVs. As these responses are lowest to DENV-4 we have used the AG129 mouse model to investigate the immunogenicity of monovalent TDV-4 or tetravalent TDV vaccines, and their efficacy against lethal DENV-4 challenge. Since the common backbone of TDV is based on an attenuated DENV-2 strain (TDV-2) we also tested the efficacy of TDV-2 against DENV-4 challenge. Single doses of the tetravalent or monovalent vaccines elicited neutralizing antibodies, anti-NS1 antibodies, and cellular responses to both envelope and nonstructural proteins. All vaccinated animals were protected against challenge at 60 days post-immunization, whereas all control animals died. Investigation of DENV-4 viremias post-challenge showed that only the control animals had high viremias on day 3 post-challenge, whereas vaccinated mice had no detectable viremia. Overall, these data highlight the excellent immunogenicity and efficacy profile of our candidate dengue vaccine in AG129 mice.

Original languageEnglish (US)
Pages (from-to)6537-6543
Number of pages7
JournalVaccine
Volume32
Issue number48
DOIs
StatePublished - Nov 12 2014

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Dengue Vaccines
Dengue virus
dengue
Vaccines
vaccines
mice
Viremia
viremia
Dengue
Neutralizing Antibodies
Antibody Formation
neutralizing antibodies
immune response
animals
Virus Diseases
Culicidae
Anti-Idiotypic Antibodies
Immunization
clinical trials
immunization

Keywords

  • AG129 mice
  • Dengue
  • Dengue 4
  • Immune protection
  • Vaccines

ASJC Scopus subject areas

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

Cite this

Investigating the efficacy of monovalent and tetravalent dengue vaccine formulations against DENV-4 challenge in AG129 mice. / Fuchs, Jeremy; Chu, Haiyan; O'Day, Peter; Pyles, Richard; Bourne, Nigel; Das, Subash C.; Milligan, Gregg; Barrett, Alan; Partidos, Charalambos D.; Osorio, Jorge E.

In: Vaccine, Vol. 32, No. 48, 12.11.2014, p. 6537-6543.

Research output: Contribution to journalArticle

Fuchs, Jeremy ; Chu, Haiyan ; O'Day, Peter ; Pyles, Richard ; Bourne, Nigel ; Das, Subash C. ; Milligan, Gregg ; Barrett, Alan ; Partidos, Charalambos D. ; Osorio, Jorge E. / Investigating the efficacy of monovalent and tetravalent dengue vaccine formulations against DENV-4 challenge in AG129 mice. In: Vaccine. 2014 ; Vol. 32, No. 48. pp. 6537-6543.
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