TY - JOUR
T1 - A single dose of any of four different live attenuated tetravalent dengue vaccines is safe and immunogenic in flavivirus-naive adults
T2 - A randomized, double-blind clinical trial
AU - Durbin, Anna P.
AU - Kirkpatrick, Beth D.
AU - Pierce, Kristen K.
AU - Elwood, Daniel
AU - Larsson, Catherine J.
AU - Lindow, Janet C.
AU - Tibery, Cecilia
AU - Sabundayo, Beulah P.
AU - Shaffer, Donna
AU - Talaat, Kawsar R.
AU - Hynes, Noreen A.
AU - Wanionek, Kimberli
AU - Carmolli, Marya P.
AU - Luke, Catherine J.
AU - Murphy, Brian R.
AU - Subbarao, Kanta
AU - Whitehead, Stephen S.
N1 - Funding Information:
The trial was funded by the NIAID Intramural Research Program, National Institutes of Health. The Regulatory Compliance Human Subjects Protection Branch (RCHSPB) of the National Institutes of Health acted as the Sponsor of the trial. RCHSPB was not involved in the study design; however, they did review the clinical protocol and consent form prior to submission of the Investigational New Drug Application to ensure compliance with the Code of Federal Regulations (21 CFR 50). RCHSPB was not involved in the data analysis or in generation of this paper.
Funding Information:
Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID) Intramural Research Program, National Institutes of Health (contract HHSN272200900010C). Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
PY - 2013
Y1 - 2013
N2 - Background. Dengue virus (DENV) causes hundreds of millions of infections annually. Four dengue serotypes exist, and previous infection with one serotype increases the likelihood of severe disease with a second, heterotypic DENV infection.Methods. In a randomized, placebo-controlled study, the safety and immunogenicity of 4 different admixtures of a live attenuated tetravalent (LATV) dengue vaccine were evaluated in 113 flavivirus-naive adults. Serum neutralizing antibody levels to all 4 dengue viruses were measured on days 0, 28, 42, and 180.Results. A single dose of each LATV admixture induced a trivalent or better neutralizing antibody response in 75%-90% of vaccinees. There was no significant difference in the incidence of adverse events between vaccinees and placebo-recipients other than rash. A trivalent or better response correlated with rash and with non-black race (P <. 0001). Black race was significantly associated with a reduced incidence of vaccine viremia.Conclusions. TV003 induced a trivalent or greater antibody response in 90% of flavivirus-naive vaccinees and is a promising candidate for the prevention of dengue. Race was identified as a factor influencing the infectivity of the LATV viruses, reflecting observations of the effect of race on disease severity in natural dengue infection.Clinical Trials Registration NCT01072786.
AB - Background. Dengue virus (DENV) causes hundreds of millions of infections annually. Four dengue serotypes exist, and previous infection with one serotype increases the likelihood of severe disease with a second, heterotypic DENV infection.Methods. In a randomized, placebo-controlled study, the safety and immunogenicity of 4 different admixtures of a live attenuated tetravalent (LATV) dengue vaccine were evaluated in 113 flavivirus-naive adults. Serum neutralizing antibody levels to all 4 dengue viruses were measured on days 0, 28, 42, and 180.Results. A single dose of each LATV admixture induced a trivalent or better neutralizing antibody response in 75%-90% of vaccinees. There was no significant difference in the incidence of adverse events between vaccinees and placebo-recipients other than rash. A trivalent or better response correlated with rash and with non-black race (P <. 0001). Black race was significantly associated with a reduced incidence of vaccine viremia.Conclusions. TV003 induced a trivalent or greater antibody response in 90% of flavivirus-naive vaccinees and is a promising candidate for the prevention of dengue. Race was identified as a factor influencing the infectivity of the LATV viruses, reflecting observations of the effect of race on disease severity in natural dengue infection.Clinical Trials Registration NCT01072786.
KW - clinical trial
KW - dengue vaccine
KW - live attenuated tetravalent
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U2 - 10.1093/infdis/jis936
DO - 10.1093/infdis/jis936
M3 - Article
C2 - 23329850
AN - SCOPUS:84874264885
SN - 0022-1899
VL - 207
SP - 957
EP - 965
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -