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Methods for vaccinating against malaria

A technology against malaria and vaccines, applied in botany equipment and methods, against vector-borne diseases, animal repellants, etc.

Inactive Publication Date: 2005-12-28
GLAXOSMITHKLINE BIOLOGICALS SA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Specifically, based on the results of clinical trials using the PfCSP vaccine or the RTS,S vaccine, neither vaccine alone was able to establish a sustainable immune response that elicited CD8+ T cells, CD4+ T cells, and antibodies against CSP

Method used

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  • Methods for vaccinating against malaria
  • Methods for vaccinating against malaria
  • Methods for vaccinating against malaria

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0095] Boosting of primed anti-PfCSP responses with RTS,S vaccine

[0096] Twenty-four HLA-A*0201 positive volunteers were recruited for this study. To allow intergroup comparisons of genetically restricted T cell responses, volunteers' HLA diversity was restricted to the most common class I HLA subtype in the population. None of these volunteers had previous exposure to malaria. Among the 24 subjects, 10 participated in the above-mentioned second PfCSP vaccine clinical trial. During this trial, these volunteers had received a total of three doses of PfCSP DNA vaccine (VCL-2510, prepared by Vical, Inc (SanDiego, CA) as previously described (62)) at a dose of 2500 μg / dose with intervals between doses. 4 weeks (62). Therefore, in this trial, these 10 volunteers received their last dose of DNA vaccine 12-14 months before receiving the booster RTS,S vaccine. The remaining 14 volunteers had not previously received PfCSP DNA vaccine and thus served as unprimed controls. All 2...

Embodiment 2

[0102] CTL response

[0103] As noted above, immunization with the RTS,S vaccine alone induced antibodies and CD4 + T cell-dependent IFN-γ responses, but have not been reported to elicit antigen-specific CTLs in humans (61). To determine whether DNA-induced memory CTLs could be recalled by boosting with the RTS,S vaccine and whether the boosted response was broader than the initial DNA-induced response, the cytotoxic activity of antigen-specific CTLs was tested in different volunteers. Peripheral blood mononuclear cells (PBMCs) were collected from the blood of DNA-primed or non-primed volunteers 1–2 weeks before immunization with RTS,S and 1 or 2 weeks after the first and / or second dose of RTS,S immunization. ). These PBMCs were then used in a chromium release assay to detect lysis of antigen-presenting target cells (105).

[0104] In vitro chromium release assays were performed as previously described (105). Specifically, to generate effector cells, 20% of the total PBM...

Embodiment 3

[0116] T cell IFN-γ response to PfCSp

[0117] IFN-γ responses were assessed using a standard ELISPOT assay as follows. The number of IFN-γ producing PfCSP-specific cells was determined by ELISPOT after 36 hours of in vitro stimulation in the presence of 10 μg / ml peptide as previously described (107). The number of spots corresponding to cytokine-producing cells (spot-forming cells; SFC) in the wells was counted using an automated spot counting system (Scanalytics, Fairfax, VA). The reaction is expressed as SFC / 10 6 The average number of PMBCs was considered significant if the following conditions were met: 1) the average number of cells in the wells containing the experimental peptide was significantly greater than that in the wells containing the control peptide (p<0.05, student's T test); 2) the net SFCs / Wells (average number of SFCs in test peptide wells minus mean number of SFCs in control peptide wells) ≥ 5 SFCs / well; and 3) stimulation index (average number of SFCs...

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Abstract

The present invention relates to methods of combating malaria infection by vaccination. The methods of the present invention involve the use of a DNA-based vaccine to elicit an anti-malarial immune response and the use of a protein-based vaccine to boost that response. The methods of the invention also involve broadening the resulting immune response by boosting with a protein-based vaccine.

Description

[0001] Cross References to Related Applications [0002] This application is based on U.S. Provisional Application S.N.60 / 420,265 (Attorney Docket No. 4012.6001) filed on October 23, 2002 and U.S. Provisional Application S.N.60 / 447,026 (Attorney Docket No. 4012.6002) filed on February 13, 2003, and claim its rights. This application is based on the entire disclosure of these provisional applications, which are hereby incorporated by reference. Background technique [0003] Malaria is one of the most serious public health problems in the tropics and subtropics. In the developing world, 3 to 5 million people are newly infected with Plasmodium each year, and up to 2.7 million people die from malaria (110). Plasmodium falciparum is the Plasmodium species responsible for most deaths caused by malaria. [0004] The life cycle of Plasmodium falciparum has four distinct stages, three of which are present in the human body. See 115 generally. In the first stage, mosquitoes carryin...

Claims

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Application Information

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IPC IPC(8): A01N43/04
CPCY02A50/30
Inventor S·L·霍夫曼R·王J·E·爱泼斯坦J·D·科恩
Owner GLAXOSMITHKLINE BIOLOGICALS SA
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