Skip to main content

Currently Skimming:


Pages 169-210

The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.


From page 169...
... 9Vaccines WHERE WE WANT TO BE IN THE YEAR 2010 After years of research, several different malaria vaccines will be available and licensed for use in humans. For infants and children in highly endemic regions of the world, an inexpensive, safe, and stable vaccine that gives long-lasting protection from death and severe clinical illness will be integrated into existing immunization programs.
From page 170...
... with irradiated sporozoites can protect humans against malaria, suggesting that immunization with appropriate sporozoite and liver-stage antigens can prevent infection in individuals bitten by malaria-infected mosquitos. In addition, repeated natural infections with the malaria parasite induce immune responses that can prevent disease and death in infected individuals, and the administration of serum antibodies obtained from repeatedly infected adults can control malaria infections in children who have not yet acquired protective immunity.
From page 171...
... the result of many studies done in animals with what happens in human malaria infection. The promises of modern vaccinology, while potentially revolutionary, have so far proved elusive.
From page 172...
... cytes and free in the circulation prior to invading other erythrocytes; the asexual parasite that develop within red blood cells; exogenous parasite material released from infected erytrocytes; and the sexual-stage parasite, which occurs both inside erythrocytes and in mosquitoes. The optimal vaccine would include antigens from the sporozoites, asexual, and sexual stages of the parasite, thus providing multiple levels of control, but vaccines effective against individual stages could also prove highly useful.
From page 173...
... (attenuated) confers protection against subsequent sporozoite-induced malaria infection in mice, monkeys, and humans (Nussenzweig et al., 1967; Clyde et al., 1973a,b,1975; Rieckmann et al., 1974, 1979; Gwadz et al., 1979)
From page 174...
... The mechanisms by which antibodies confer protection are not certain. Antibodies can prevent the invasion of sporozoites into liver cells in culture (Hollingdale et al., 1984; Mazier et al., 1986)
From page 175...
... 1968a,b) , or administration of purified gamma-interferon (Maheshwari et al., 1986; Schofield et al., 1987a)
From page 176...
... parasites (Chulay, 1989) , which facilitates the testing of vaccines in various animal model systems.
From page 177...
... Other Sporozoite Proteins Antibodies directed against other sporozoite antigens can inhibit sporozoite invasion into liver cells in culture, and when administered to mice can protect them from sporozoite-induced malaria (Hollingdale et al., 1990)
From page 178...
... insertion of the CS protein gene into attenuated strains of Salmonella creates a vaccine that can protect mice from sporozoite-induced malaria (Sadoff et al., 1988; Aggarwal et al., 1990)
From page 179...
... nine amino acids of the CS repeat section that contained only the repetitive amino acids of the CS protein induced high levels of antisporozoite antibodies in monkeys and humans (Collins et al., 1989: Gordon et al., 1990) , but these antibodies were not directed against the four-amino-acid B-cell epitope recognized by the protective monoclonal antibody (Charoenvit et al., 1991b)
From page 180...
... coupled to a lipid structure (Deres et al., 1989)
From page 181...
... protein that binds to T-cell epitopes. This means that only the T lymphocytes of some individuals (those with suitable MHC proteins)
From page 182...
... include the use of adjuvants that increase the antibody response, so that protective levels of antibody are maintained for longer periods; the addition of helper T-cell epitopes from malaria antigens to boost antibody levels after natural exposure to sporozoites; and the use of new vaccine formulations that provide prolonged release of antigen, thereby providing their own booster doses over time. It must be acknowledged that such formulations have not been developed for any vaccine and represent a considerable technological challenge.
From page 183...
... Figure 9-2 Hypothetical course of Plasmodium falciparum infection in a nonimmune individual (A) and the effect of various levels of host immunity to sporozoites (B)
From page 184...
... in older children and adults, illness and death caused by malaria decrease with increasing exposure. This immunity is mediated primarily by antibodies against blood-stage parasites, and children with P
From page 185...
... Chulay et al., 1981) , by blocking the binding of merozoites to erythrocytes (Thomas et al., 1984; Sim et al., 1990)
From page 186...
... Antibodies also could react with parasite antigens, released from infected erythrocytes, that mediate the disease process (Playfair et al., 1990)
From page 187...
... to the glycophorins (Mitchell et al., 1986)
From page 188...
... Plasmodium species can invade by binding to one of several erythrocyte receptors, a multivalent vaccine will be required to completely inhibit merozoite invasion of red blood cells. Rhoptries and micronemes are organelles located near the anterior end of the merozoite.
From page 189...
... Antigens That Induce Protective Immunity in Animal Models A number of animal malarias, such as those caused by P chabaudi and P
From page 190...
... Preclinical and Clinical Trials To date, the only reported human trials of asexual-stage malaria vaccines have been performed by Dr. Patarroyo and his colleagues in Colombia (Patarroyo et al., 1988)
From page 191...
... may increase 10- or 20-fold during the next cycle of asexual development, and parasitemias of about 1 percent may be associated with severe disease and some risk of death, despite appropriate treatment. Vaccines that control infection only after higher levels of parasitemia are reached would not be recognized in such a trial, even though such vaccines might be beneficial in partially immune individuals who were tolerant to modest levels of parasitemia.
From page 192...
... There is considerable evidence that MSA-1 is the target of a protective immune response. Two groups have reported that human monoclonal antibodies against P
From page 193...
... Mechanisms of Immunity Antibodies Sera from animals immunized with gametocyte-rich blood develop antibodies that, when mixed with gametocytes before ingestion by mosquitoes, will inhibit parasite development and maturation to oocysts within the mosquito (Carter and Chen, 1976; Gwadz, 1976)
From page 194...
... by zygotes (Kaslow et al., 1988)
From page 195...
... be able to rely on natural boosting after primary immunization with a transmission-blocking vaccine. The use of novel adjuvants, carrier proteins, and slow-release vaccine formulations may overcome this problem.
From page 196...
... midgut extracts (Alger and Cabrera, 1972)
From page 197...
... RESEARCH FOCUS: Expanded studies in humans, including further immunization trials with radiation-attenuated sporozoites, to characterize the mechanisms of protective immunity. Identification of antigens that are targets of protective immunity is incomplete.
From page 198...
... RESEARCH FOCUS: Better methods of assessing vaccine efficacy, with consideration given to conducting well-designed human vaccine trials at an early stage of antigen assessment. In Vitro Assays There is an immediate need for validated, reproducible, quantitative in vitro assays that correlate with and are predictive of protective immunity in humans.
From page 199...
... Alger, N
From page 200...
... Carter, R., P
From page 201...
... Cohen, S., I
From page 202...
... exoerythrocytic forms of malaria parasites by gamma-interferon. Science 232:881–884.
From page 203...
... Gwadz, R
From page 204...
... Holder, A
From page 205...
... Keister.
From page 206...
... Trosper, C
From page 207...
... Peiris, J
From page 209...
... S.P. Chang, E

Key Terms



This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More information on Chapter Skim is available.