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3 Malaria Vaccines
Pages 21-40

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From page 21... ... While both types of vaccine would also reduce transmission, it is also theoretically feasible to protect communities by high coverage with vaccines that would generate immune responses to sexual stages in the blood of humans and that would then interfere with completion of the life cycle when anophelines consume the blood of such vaccinated humans. However, the latter type of vaccine is not immediately useful for individual protection as would be required by the Department of Defense (DoD) Read the entire page →
From page 23... ... 23 by the ) , .The the host release sexual blood a release inoculates and relapses cells into (ookinetes) Read the entire page →
From page 24... ... falciparum vaccine program, as it is the most severe and urgent problem. However, prevention of the clinical debilitation of P Read the entire page →
From page 25... ... bThe level of protection required has been estimated by the Malaria Vaccine Technology Working Group, a recently formed consensus group (Roadmap, 2006) Read the entire page →
From page 26... ... Malaria Vaccine Program researchers. The following information illustrates the depth of experience in the MIDRP Malaria Vaccine Program and their collaborators as well as the fact that current promising candidates have emerged from a long and sustained effort over the last 30 years (Appendix A) Read the entire page →
From page 27... ... . CSP remains a primary vaccine candidate, either alone or in combination with other preerythrocytic- or erythrocytic-stage antigens, in vaccine development programs of the Walter Reed Army Institute of Research (WRAIR) Read the entire page →
From page 28... ... Subsequent clinical trials by WRAIR examined CSP repeats using various conjugates including fusion with 81 amino acids from a nonstructural protein of influenza (R32NS1) , adjuvanted with monophosphoryl lipid A(MPL) Read the entire page →
From page 29... ... . However, clinical trials of these candidate vaccines when used alone or in repeated homologous boosting regimes have been disappointing, with low levels of antibody and minimal protection (Le et al., 2000; Wang et al., 1998) Read the entire page →
From page 30... ... . More recently, phase 2 clinical trials of a combination vaccine composed of MSP-1, MSP-2, and RESA, a ring-infected erythrocyte surface antigen expressed on erythrocytes, demonstrated a 62 percent reduction in parasite density with a lower prevalence of parasites expressing the MSP-2 allele found in the vaccine (Genton et al., 2002) Read the entire page →
From page 31... ... . However, in the experimental challenge model, RTS,S protective efficacy was not increased by a combination of RTS,S + MSP-1, and immunization with RTS,S + SSP2/TRAP resulted in reduced vaccine efficacy (Heppner et al., 2005; Heppner, 2006) Read the entire page →
From page 32... ... Understanding parasite population structure and antigenic variation in nature requires lengthy and difficult field and laboratory studies, some of which are currently underway by other groups. Lack of Understanding of Protective Immunity A second major problem is the lack of understanding of the mechanisms of immune protection from malaria (Good, 2001) Read the entire page →
From page 33... ... . The MIDRP Malaria Vaccine Program could contribute significantly by developing jointly agreed criteria about the appropriateness of different animal models and outcome measurements in order to assist the global community in defining joint go/no-go criteria for vaccine candidates. Read the entire page →
From page 34... ... Producing points comparable field metrics can extend the value of clinical trials beyond the efficacy of a particular vaccine candidate. Improving 6. Read the entire page →
From page 35... ... The MIDRP Malaria Vaccine Program researchers also demonstrated the importance of the CSP central repeats in generating protective antibodies as well as the necessity for cell-mediated immune responses in protection, with target epitopes in the CSP C-terminal region (Aggarwal et al., 1990; Malik et al., 1991; Sadoff et al., 1988) Read the entire page →
From page 36... ... . In addition to the ability to conduct human clinical trial challenges, the MIDRP Malaria Vaccine Program labs have contributed immensely to standardizing animal models of malaria, including the P Read the entire page →
From page 37... ... 37 MIDRP of extent 2005. Read the entire page →
From page 38... ... . It can also be seen from Figure 3-2 that the MIDRP Malaria Vaccine Program is involved in the development of about half of the vaccine candidates that have not yet reached phase 2 trials but are under active development. Read the entire page →
From page 39... ... 39 malaria, et 18 clinical 2005 to Alonso al., (up months) malaria et 6 infection, 2004 to Alonso al., (up months) Read the entire page →
From page 40... ... . It was encouraging that RTS,S also showed significant protection against severe malaria in children, estimated at 58 percent (95 percent CI: 16�81 percent) Read the entire page →

From page 21...

... While both types of vaccine would also reduce transmission, it is also theoretically feasible to protect communities by high coverage with vaccines that would generate immune responses to sexual stages in the blood of humans and that would then interfere with completion of the life cycle when anophelines consume the blood of such vaccinated humans. However, the latter type of vaccine is not immediately useful for individual protection as would be required by the Department of Defense (DoD)

3 Malaria Vaccines Pages 21-40

3 Malaria Vaccines
Pages 21-40