Strategy for development of a pre-erythrocytic Plasmodium falciparum DNA vaccine for human use

被引：38

作者：

Hoffman, SL ^{[1
]}

Doolan, DL ^{[1
]}

Sedegah, M ^{[1
]}

Aguiar, JC ^{[1
]}

Wang, RB ^{[1
]}

Malik, A ^{[1
]}

Gramzinski, RA ^{[1
]}

Weiss, WR ^{[1
]}

Hobart, P ^{[1
]}

Norman, JA ^{[1
]}

Margalith, M ^{[1
]}

Hedstrom, RC ^{[1
]}

机构：

[1] VICAL INC,SAN DIEGO,CA 92121

来源：

VACCINE | 1997年 / 15卷 / 08期

关键词：

DNA vaccine; malaria; pre-erythrocytic stage;

D O I：

10.1016/S0264-410X(96)00273-3

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Data generated in the Plasmodium yoelii rodent model indicated that plasmid DNA vaccines encoding the P. yoelii circumsporozoite protein (PyCSP) or 17 kDa hepatocyte erythrocyte protein (PyHEP17) were potent inducers of protective CD8(+) T cell responses directed against infected hepatocytes. Immunization with a mixture of these plasmids circumvented the genetic restriction of protective immunity and induced additive protection. A third DNA vaccine encoding the P. yoelii sporozoite surface protein 2 (PySSP2) also induced protection. The P. falciparum genes encoding the homologues of these three protective P. yoelii antigens as well as another P. falciparum gene encoding a protein that is expressed in infected hepatocytes have been chosen for the development of a human vaccine. The optimal plasmid constructs for human use will be selected on the basis of immunogenicity data generated in mice and nonhuman primates. We anticipate that optimization of multi-gene P. falciparum DNA vaccines designed to protect against malaria by inducing CD8(+) cells that target infected hepatocytes will require extensive clinical trials during the coming years. Published by Elsevier Science Ltd.

引用

页码：842 / 845

页数：4

共 10 条

[1] PLASMODIUM-YOELII - 17-KDA HEPATIC AND ERYTHROCYTIC STAGE PROTEIN IS THE TARGET OF AN INHIBITORY MONOCLONAL-ANTIBODY [J].