Heterotypic dengue infection with live attenuated monotypic dengue virus vaccines: Implications for vaccination of populations in areas where dengue is endemic

Anna P Durbin, Alexander Schmidt, Dan Elwood, Kimberli A. Wanionek, Janece Lovchik, Bhagvanji Thumar, Brian R. Murphy, Stephen S. Whitehead

Research output: Contribution to journalArticle

Abstract

Background. Because infection with any of the 4 Dengue virus serotypes may elicit both protective neutralizing antibodies and nonneutralizing antibodies capable of enhancing subsequent heterotypic Dengue virus infections, the greatest risk for severe dengue occurs during a second, heterotypic Dengue virus infection. It remains unclear whether the replication of live attenuated vaccine viruses will be similarly enhanced when administered to Dengue-immune individuals. Methods. We recruited 36 healthy adults who had previously received a monovalent live Dengue virus vaccine 0.6-7.4 years earlier. Participants were assigned to 1 of 4 cohorts and were randomly chosen to receive placebo or a heterotypic vaccine. The level of replication, safety, and immunogenicity of the heterotypic vaccine virus was compared with that of Dengue virus immunologically naive vaccinees. Results. Vaccine virus replication and reactogenicity after monovalent Dengue virus vaccination in naive and heterotypically immune vaccinees was similar. In contrast to naive vaccinees, the antibody response in heterotypically immune vaccinees was broadly neutralizing and mimicked the response observed by natural secondary Dengue virus infection. Conclusions. Enhanced replication of these live attenuated Dengue virus vaccines was minimal in heterotypically immune vaccinees and suggests that the further evaluation of these candidate vaccines in populations with preexisting DENV immunity can proceed safely. Clinical trials registration: NCT00458120 (http://www.clinicaltrials.gov/ct2/show/NCT00458120).

Original languageEnglish (US)
Pages (from-to)327-334
Number of pages8
JournalJournal of Infectious Diseases
Volume203
Issue number3
DOIs
StatePublished - Feb 1 2011

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Dengue Vaccines
Dengue Virus
Dengue
Vaccination
Infection
Population
Virus Diseases
Attenuated Vaccines
Vaccines
Viruses
Severe Dengue
Blocking Antibodies
Virus Replication
Neutralizing Antibodies
Antibody Formation
Immunity
Placebos
Clinical Trials
Safety

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Heterotypic dengue infection with live attenuated monotypic dengue virus vaccines : Implications for vaccination of populations in areas where dengue is endemic. / Durbin, Anna P; Schmidt, Alexander; Elwood, Dan; Wanionek, Kimberli A.; Lovchik, Janece; Thumar, Bhagvanji; Murphy, Brian R.; Whitehead, Stephen S.

In: Journal of Infectious Diseases, Vol. 203, No. 3, 01.02.2011, p. 327-334.

Research output: Contribution to journalArticle

Durbin, Anna P ; Schmidt, Alexander ; Elwood, Dan ; Wanionek, Kimberli A. ; Lovchik, Janece ; Thumar, Bhagvanji ; Murphy, Brian R. ; Whitehead, Stephen S. / Heterotypic dengue infection with live attenuated monotypic dengue virus vaccines : Implications for vaccination of populations in areas where dengue is endemic. In: Journal of Infectious Diseases. 2011 ; Vol. 203, No. 3. pp. 327-334.
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