Multi-component-multistage malaria vaccines

Patent metadata

Field	Value
Publication number	US-10183066-B2
Application number	US-201515129230-A
Country	US
Kind code	B2
Filing date	Mar 27, 2015
Priority date	Mar 28, 2014
Publication date	Jan 22, 2019
Grant date	Jan 22, 2019

Abstract

The present disclosure relates to novel malaria vaccines composed of different recombinant proteins, in particular recombinant fusion proteins comprising several different Plasmodium falciparum antigens from the pre-erythrocytic the blood, and the sexual parasite stages. The proteins and/or fusion proteins will be used in a mixture vaccine formulation to elicit protective immune responses in humans. Nucleic acid molecules encoding said recombinant proteins, vectors, host cells containing the nucleic acids and methods for preparation and producing such proteins; Antibodies induced or generated by the use of said malaria vaccines or said nucleic acid molecules encoding said proteins and/or fusion proteins and the use of such antibodies or recombinant derivatives for passive immunotherapy.

First claim

What is claimed is:

1. A mixture of recombinant proteins suitable as an immunogenic composition for inducing an immune response in a human against the parasite Plasmodium falciparum comprising antigens from Plasmodium falciparum surface proteins of the pre-erythrocytic, the blood-, and the sexual-stage of the parasite life cycle, the mixture comprising:
a) a fusion protein of the pre-erythrocytic antigens PfCelTOS, a TSR-domain of PfCSP (PfCSP_TSR) and a TSR-domain of PfTRAP (PfTRAP_TSR), wherein the fusion protein comprises an amino acid sequence of at least 90% sequence identity to SEQ ID NO. 1;
b) a blood stage antigen(s) comprising at least one variant of Apical membrane antigen 1 (PfAMA1), or fragments thereof; and
c) a sexual stage antigen(s) comprising the ookinete antigen Pfs25 and/or the gamete/gametocyte surface protein fragment Pf230C0.

2. The mixture according to claim 1 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO. 1.

3. The mixture according to claim 1 , wherein the sexual stage antigen comprises a fusion protein of Pfs25 and Pf230C0.

4. The mixture according to claim 1 , wherein the blood stage antigens comprise at least a further Plasmodium falciparum blood stage antigen.

5. The mixture according to claim 4 , wherein the further Plasmodium falciparum blood stage antigen is selected from the group consisting of PfMsp1, PfRIPR, PfRh2, PfMsp4, PfMsp8, PfRh5, and PfMsp3.

6. The mixture according to claim 4 , wherein the further Plasmodium falciparum blood stage antigen is selected from the group consisting of PfMsp1-19, PfRIPR_EGF7/8, PfRh2, PfRh5a (Peptide), PfRh5b (Peptide), and N-terminal fragment of PfMsp3.

7. The mixture according to claim 1 , wherein the blood stage antigens comprise PfAMA1-DICO1, PfAMA1-DICO2, and PfAMA1-DICO3.

8. The mixture according to claim 1 , wherein the blood stage antigens comprise:
i) PfAMA1-DICO1 and PfMsp1-19;
ii) PfAMA1-DICO2 and PfRh2; and
iii) PfAMA1-DICO3, PfRIPR_EGF7/8.

9. The mixture according to claim 1 , wherein the blood stage antigens comprise PfAMA1-DICO1, PfAMA1-DICO2, and PfAMA1-DICO3, and wherein the sexual stage antigens comprise Pfs25 and Pfs230C0.

10. A mixture of recombinant proteins suitable as an immunogenic composition for inducing an immune response in a human against the parasite Plasmodium falciparum comprising antigens from Plasmodium falciparum surface proteins of the pre-erythrocytic, the blood-, and the sexual-stage of the parasite life cycle, the mixture comprising:
a) a fusion protein of the pre-erythrocytic antigens PfCelTOS, a TSR-domain of PfCSP (PfCSP_TSR) and a TSR-domain of PfTRAP (PfTRAP_TSR), wherein the fusion protein comprises the amino acid sequence of SEQ ID NO. 26;
b) blood stage antigens comprising variants of Apical membrane antigen 1 (PfAMA1), wherein the blood stage antigens comprise a polypeptide comprising the amino acid sequence of SEQ ID NO. 11, a polypeptide comprising the amino acid sequence of SEQ ID NO. 12 and a polypeptide comprising the amino acid sequence of SEQ ID NO. 13; and
c) sexual stage antigens comprising the ookinete antigen Pfs25 and gamete/gametocyte surface protein fragment Pf230C0, wherein the sexual stage antigens comprise a polypeptide comprising the amino acid sequence of SEQ ID NO. 8.

11. The mixture according to claim 1 , wherein the blood stage antigens comprise PfAMA1-DICO1, PfAMA1-DICO2, and PfAMA1-DICO3, and wherein the sexual stage antigens comprise Pfs25, Pfs230C0 and PfRh5b.

12. A mixture of recombinant proteins suitable as an immunogenic composition for inducing an immune response in a human against the parasite Plasmodium falciparum comprising antigens from Plasmodium falciparum surface proteins of the pre-erythrocytic, the blood-, and the sexual-stage of the parasite life cycle, the mixture comprising:
a) a fusion protein of the pre-erythrocytic antigens PfCelTOS, a TSR-domain of PfCSP (PfCSP_TSR) and a TSR-domain of PfTRAP (PfTRAP_TSR), wherein the fusion protein comprises the amino acid sequence of SEQ ID NO. 9;
b) blood stage antigens comprising variants of Apical membrane antigen 1 (PfAMA1), wherein the blood stage antigens comprise a polypeptide comprising the amino acid sequence of SEQ ID NO. 11, a polypeptide comprising the amino acid sequence of SEQ ID NO. 12 and a polypeptide comprising the amino acid sequence of SEQ ID NO. 13; and
c) the sexual stage antigens comprising the ookinete antigen Pfs25 and gamete/gametocyte surface protein fragment Pf230C0, wherein the sexual stage antigens comprise a polypeptide comprising the amino acid sequence of SEQ ID NO. 28.

13. An immunogenic composition for inducing an immune response in human individuals against Plasmodium falciparum comprising as an active ingredient the mixture of claim 1 and a carrier in a physiologically acceptable medium.

14. The immunogenic composition according to claim 13 , wherein the composition further comprises an adjuvant in an amount sufficient to enhance an immune response.

Assignees

• Fraunhofer Ges Forschung
• Fraunhofer Ges Forschung

Inventors

• Boes Alexander
• Spiegel Holger
• Edgue Gueven
• Beiss Veronique
• Sack Markus
• Reimann Andreas
• Fischer Rainer

Classifications

• A61K2039/70

  Multivalent vaccine · CPC title

• A61K2039/575

  humoral response · CPC title

• A61P33/06

  Antimalarials · CPC title

• C07K2319/21

  containing a His-tag · CPC title

• C07K16/205

  Plasmodium · CPC title