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Protein copolymer malaria vaccine
| Details |
Inventors: Patarroyo, Manuel E.;
Assignee:
Primary Examiner: Schain; Howard E.
Assistant Examiner: Perkins; Susan M.
Attorney, Agent or Firm: Abelman Frayne Rezac & Schwab
A mixture of the synthetic peptide compounds of the formulas: Formula (I) Tyr-Gly-Gly-Pro-Ala-Asn-Lys-Lys-Asn-Ala-Gly-OH, Formula (II) Asp-Glu-Leu-Glu-Ala-Glu-Thr-Gln-Asn-Val-Tyr-Ala-Ala-NH.sub.2, and Formula (III) Tyr-Ser-Leu-Phe-Gln-Lys-Glu-Lys-Met-Val-Leu-NH.sub.2, and compositions thereof, induces antibodies against the late stages of Plasmodium faciparum malaria and provides protection against infection with this parasite, thus providing a synthetic malaria vaccine for Plasmodium falciparum induced malaria. A synthetic protein copolymer vaccine, polymerized from a monomer which is a hybrid of formulas (II), (III) and (I), and which also includes the (Asn-Ala-Asn-Pro) sequence of the CS protein between formulas (II) and (III) and Formulas (III) and (I) of the monomer, has been shown to provide safe and complete self-limiting protection in human volunteers against the asexual blood stages of P. faciparum induced malaria. |
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DETAILED DESCRIPTION OF THE INVENTION It has been established that a mixture of the following novel peptide compounds represents a preferred embodiment of the present invention, namely, Formula (I) Tyr-Gly-Gly-Pro-Ala-Asn-Lys-Lys-Asn-Ala-Gly-OH, Formula (II) Asp-Glu-Leu-Glu-Ala-Glu-Thr-Gln-Asn-Val-Tyr-Ala-Ala-NH.
sub.
2, and Formula (III) Tyr-Ser-Leu-Phe-Gln-Lys-Glu-Lys-Met-Val-Leu-NH.
sub.
2, when employed in about a 1:1:1 mixture, weight-by-weight, up to about a 10:10:10 mixture, weight-by-weight, provide a synthetic vaccine which has been found to provide complete protective immunity against P.
falciparum induced malaria.
The protein copolymer of the present invention is comprised of: (1) the peptide SPf 55.
1, which consists of a chain of 13 amino acids, which is the same as Formula (II) above; (2) the (Asn-Ala-Asn-Pro) epitope of the P.
falciparum circumsporozoite protein; (3) the peptide SPf 83.
1, which consists of a chain of 11 amino acids, which is the same as Formula (III) above; (4) the (Asn-Ala-Asn-Pro) epitope of the P.
falciparum circumsporozoite protein, and (5) the peptide SPf 35.
1, which consists of a chain of 8 amino acids, which is the same as Formula (I) above except for the absence Tyr-Gly-Gly at the beginning of the peptide.
During the synthesis of the protein copolymer the amino acids Tyr-Gly-Gly were omitted to allow the molecule to assume an appropriate steric configuration to provide it with the same immunogenic properties possessed by the parasite.
Additionally, cysteines (CS) were added at the amino and carboxy terminal ends, with Gly and Pro employed as spacers, as indicated in Formula (VII).
The molecular mass of Formula (VI) is about 5000 Daltons.
When polymerized via the cysteine bridges, or bonds, it is preferred that it be polymerized to about 150 Kilodaltons, namely, about thirty (30) times its monomeric mass.
While it has been found that when x equals 30 in Formula (VII) the protein copolymer has optimum stability and immunogenicity, based on the combination of solubility and size of the molecule, x can vary from 2 to about 50 without any significant sacrifice or loss in its immunogenic response
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