TY - JOUR
T1 - A chimeric tetravalent dengue DNA vaccine elicits neutralizing antibody to all four virus serotypes in rhesus macaques
AU - Raviprakash, Kanakatte
AU - Apt, Doris
AU - Brinkman, Alice
AU - Skinner, Craig
AU - Yang, Shumin
AU - Dawes, Glenn
AU - Ewing, Dan
AU - Wu, Shuenn Jue
AU - Bass, Steve
AU - Punnonen, Juha
AU - Porter, Kevin
N1 - Funding Information:
We are grateful to Dr. Peter O'Hanley for his support and expert advice. This work was funded by a cooperative research and development agreement between the Naval Medical Research Center and Maxygen Inc., and by the Bill and Melinda Gates Foundation. The initial work to generate shuffled dengue antigens was supported by a grant from the Defense Advanced Research Projects Agency (DARPA). The experiments reported herein were conducted according to the principles set forth in the “Guide for the Care and Use of Laboratory Animals”, Institute of Laboratory Animals Resources, National Research Council, DHHS Publication No. (NIH) 86-23 (1985). The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position or the Department of the Navy, Department of Defense nor the U.S. Government.
PY - 2006/9/15
Y1 - 2006/9/15
N2 - DNA shuffling and screening technologies were used to produce chimeric DNA constructs expressing antigens that shared epitopes from all four dengue serotypes. Three shuffled constructs (sA, sB and sC) were evaluated in the rhesus macaque model. Constructs sA and sC expressed pre-membrane and envelope genes, whereas construct sB expressed only the ectodomain of envelope protein. Five of six, and four of six animals vaccinated with sA and sC, respectively, developed antibodies that neutralized all 4 dengue serotypes in vitro. Four of six animals vaccinated with construct sB developed neutralizing antibodies against 3 serotypes (den-1, -2 and -3). When challenged with live dengue-1 or dengue-2 virus, partial protection against dengue-1 was observed. These results demonstrate the utility of DNA shuffling as an attractive tool to create tetravalent chimeric dengue DNA vaccine constructs, as well as a need to find ways to improve the immune responses elicited by DNA vaccines in general.
AB - DNA shuffling and screening technologies were used to produce chimeric DNA constructs expressing antigens that shared epitopes from all four dengue serotypes. Three shuffled constructs (sA, sB and sC) were evaluated in the rhesus macaque model. Constructs sA and sC expressed pre-membrane and envelope genes, whereas construct sB expressed only the ectodomain of envelope protein. Five of six, and four of six animals vaccinated with sA and sC, respectively, developed antibodies that neutralized all 4 dengue serotypes in vitro. Four of six animals vaccinated with construct sB developed neutralizing antibodies against 3 serotypes (den-1, -2 and -3). When challenged with live dengue-1 or dengue-2 virus, partial protection against dengue-1 was observed. These results demonstrate the utility of DNA shuffling as an attractive tool to create tetravalent chimeric dengue DNA vaccine constructs, as well as a need to find ways to improve the immune responses elicited by DNA vaccines in general.
KW - Chimeric vaccines
KW - DNA vaccines
KW - Dengue vaccines
UR - http://www.scopus.com/inward/record.url?scp=33747881356&partnerID=8YFLogxK
U2 - 10.1016/j.virol.2006.05.005
DO - 10.1016/j.virol.2006.05.005
M3 - Article
C2 - 16814355
AN - SCOPUS:33747881356
SN - 0042-6822
VL - 353
SP - 166
EP - 173
JO - Virology
JF - Virology
IS - 1
ER -