HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wright, P. F. Articles by Schmidt, A. C. PubMed Articles by Wright, P. F. Articles by Schmidt, A. C.

Phase 1 Trial of the Dengue Virus Type 4 Vaccine Candidate rDEN430-4995 in Healthy Adult Volunteers

rDEN430-4995 is a live attenuated dengue virus type 4 (DENV4) vaccine candidate specifically designed as a further attenuated derivative of the rDEN430 parent virus. In a previous study, 5 of 20 vaccinees who received 10⁵ plaque-forming units (PFU) of rDEN430 developed a transient elevation of the serum alanine aminotransferase (ALT) level and an asymptomatic maculopapular rash developed in 10 of 20. In the current study, 28 healthy adult volunteers were randomized to receive 10⁵ PFU of rDEN430-4995 (20) or placebo (8) as a single subcutaneous injection. The vaccine was safe, well-tolerated, and immunogenic. An asymptomatic generalized maculopapular rash and elevations in ALT levels were observed in 10% of the rDEN430-4995 vaccinees. None of the rDEN430-4995 vaccinees became viremic, yet 95% developed a four-fold or greater increase in neutralizing antibody titers. Thus, rDEN430-4995 was demonstrated to be safe, highly attenuated, and immunogenic. However, an asymptomatic localized erythematous rash at the injection site was seen in 17/20 rDEN430-4995 vaccinees. Therefore, alternative DENV4 vaccine strains were selected for further clinical development.

Received March 13, 2009. Accepted for publication July 28, 2009.

Acknowledgments: We thank Sandra M. Yoder for excellent technical support with the cytokine bead assays; the National Institute of Allergy and Infectious Diseases Office of Clinical Research, particularly the Regulatory Compliance and Human Subjects Protection Branch, for support; and Alexander Pletnev for performing the TBEV serologic assay. This study was registered under identifier NCT00322946 at clinicaltrials.gov.

Financial support: This study was supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases, National Institutes of Health, in part through a contract with the Johns Hopkins Bloomberg School of Public Health and a subcontract with Vanderbilt University Medical Center.

^* Address correspondence to Alexander C. Schmidt, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Room 6511, Bethesda, MD 20892. E-mail: as337y{at}nih.gov

Authors’ addresses: Peter F. Wright, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756, E-mail: peter.f.wright{at}dartmouth.edu. Stephen S. Whitehead, Joseph E. Blaney, Brian R. Murphy, and Alexander C. Schmidt, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Room 6511, Bethesda, MD 20892, E-mails: swhitehead{at}niaid.nih.gov, jblaney{at}niaid.nih.gov, bmurphy{at}niaid.nih.gov, and as337y{at}nih.gov. Anna P. Durbin and Bhavin Thumar, Center for Immunization Research, Johns Hopkins School of Pulbic Health, 615 North Wolfe Street, Room E5601, Baltimore, MD 21205, E-mails: adurbin{at}jhsph.edu and bthumar{at}jhsph.edu. Mine R. Ikizler, Susan Henderson, Sharon Ankrah, and Michael T. Rock, Division of Pediatric Infectious Disease, Vanderbilt University, Nashville, TN 37232, E-mails: mine.ikizler{at}vanderbilt.edu, shende8{at}emory.edu, sharon.n.ankrah{at}vanderbilt.edu, and michael.rock{at}vanderbilt.edu. Brett A. McKinney, Department of Genetics, University of Alabama School of Medicine, 1918 University Boulevard, Birmingham, AL 35294, E-mail: brett.mckinney{at}gmail.com.