Malaria vaccines: multiple targets.
Malaria vaccines: multiple targets.
复制标题
疟疾疫苗：多个目标。
DOI：
10.1126/science.8073276
复制
发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Long,CA
中科院分区：
文献类型：
--
作者：
Nussenzweig,RS;Long,CA
1381 selected on the basis of their preferential recognition by sera from immune individuals from endemic areas. In some cases the targets of monoclonal antibodies that inhibit P. falciparum development in vitro have been used as vaccine candidates. The identification of homologous proteins in simian and rodent malarias has greatly facilitated investigation of potential antigens and their immune mechanisms. However, a biological function has been identified for only a few of these molecules, such as the CS protein, which binds to a hepatocyte receptor and mediates parasite adherence and hepatocyte invasion (7). Most studies of these antigens have been with partial or full-length polypeptides produced in recombinant expression systems. Synthetic peptides have also been used, selected either empirically or on the basis of the amino acid sequence of defined T and B cell epitopes. The first synthetic vaccine to undergo clinical trials in humans contained the immunodominant B cell epitope of the CS protein (NANP) 3 and tetanus toxoid as carrier (8). Because this synthetic vaccine as well as a recombinant CS vaccine (9) were only partially effective, a new genera-tion of CS-based vaccines is being tested. One candidate is based on multiple antigen peptides, a synthetic construct that contains multiple copies of parasite-derived T and B cell epitopes (10). MAPs can deliver larger doses of immunogen and incorporate T and B cell epitopes from more than one parasite antigen, including" universal" T cell epitopes.Another approach is derived from an immune mechanism directed toward infected hepatocytes in rodent malaria. Deletion of CD8'T cells from sporozoite-immunized mice abrogates their resistance to infection (1 1), and transfer of CD8'T cellclones, specific for the CS protein or another sporozoite antigen (SSP-2), confers resistance to sporozoite challenge (12). Because cytotoxic T cells are most efficiently in-duced by intracellular expression of proteins, recombinant bacteria and virusesare being engineered to expresskey malarial antigens or their epitopes. Recombinant Salmonella as well as recombinant influenza and vaccinia viruses expressing these CS sequences induce cytotoxic T cells, inhibit liver stages of P. falciparum, and induce resistance to malaria infections (13). The erythrocytic stages of the parasite are responsible for the pathology induced by malaria, presenting a particular challenge for vaccine development. Blood-stage para-sites are surrounded by several membrane systems and develop within erythrocytes, which lack class I and class II major histocompatibility antigens. However, bloodstage antigens can potentially protect pri-mates against P. falciparum challenge. Short
