Immunogenicity of Well-Characterized Synthetic Plasmodium ...
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Immunogenicity of Well-Characterized Synthetic Plasmodium ...

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8 Pages
English

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REPORT DOCUMENTATION PAGE. A‚… ... à Tr…‰vpr† à 9v…rp‡‚…h‡rà s‚…à D s‚… .... II ELISA plates (Dynatech Laboratories, Chantilly, Va.) ..... M.B.J. was supported by a postdoctoral fellowship from the Oak ..... http://www.who.int. 52.

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ecific (10, 22). This stage-specific nisms are operative at different stages of the parasite life cycle gene expression actually presents an opportunity to target an- (4, 10), so the ideal vaccine should combine epitopes identified tigens in several stages as potential vaccine candidates. The as strong inducers of immunity. circumsporozoite (CS) protein (5) on the surface of early sporo- Over the past several years, considerable progress has been zoites, liver-stage antigen-1 (LSA-1) (17, 23, 52), expressed made toward the development and structural design of com- when sporozoites invade liver cells, and merozoite surface pro- plex polypeptides to be used as antigens. Multiple antigen tein-1 (MSP-1) (21), expressed by late liver- and blood-stage peptide (MAP) conjugates provide a means to include differ- parasites, are among the handful of antigens that have been ent stage-specific peptides on one molecule, resulting in a shown to have stage-specific activity to target different devel- multiepitope, multistage vaccine molecule that can potentially opmental stages of the parasite and potentially lead to better lead to better protection. MAPs (11, 46) offer a very attractive protection. alternative to the conventional linear peptide approach based on a small immunologically inert core molecule of radial branching lysine residues onto which a number of peptide an- * Corresponding author. Mailing address: IOMAI Corporation, 20 tigens can be anchored. This results in a large macromoleculeFirstfield Rd., Suite 250, Gaithersburg, MD 20878. Phone: (301) 556- with a unique three-dimensional configuration which has a4521. Fax: (301) 556-4501. E-mail: rkenney@iomai.com. † Present address: NIH/NIAID/LPD, Bethesda, MD 20892. high molar ratio of peptide antigen to core molecule and does 4884 5(3257 ’2&80(17$7,21 3$*( UHGXFLQJDZDUH)RUP$SSURYHG5HSRUWV20%1R'$7(6&29(5('5(3257'$7(+HDGTXDUWHUV ''00<<<< $UOLQJWRQ5(32577<3(ODZ7,7/($1'68%7,7/(180%(5 6 D&2175$&7180%(5'HSDUWPHQW$87+25 6 IRU3(5)250,1*25*$1,=$7,211$0( 6 $1'$''5(66 (6 'DYLV6321625,1*021,725,1*$*(1&<1$0( 6 $1'$''5(66 (6