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US 12,109,258 B2Granted
Synthetic malaria immunogens, combinations thereof, and their use to prevent and treat malaria infections
AssigneesThe Trustees of the University of Pennsylvania, Ahmed S.I. Aly, Inovio Pharmaceuticals, Inc., The Wistar Institute of Anatomy and Biology
InventorsDavid Weiner, Emma Reuschel, Bernadette Ferraro, Ahmed S. I. Aly
Life of this patent
Estimating the term…
Abstract
Provided herein are sequences of Plasmodium spp. liver stage exported proteins as well as expression constructs expressing the sequences. Also provided herein are methods for generating an immune response against malaria using the expression constructs provided herein.
Claims12
A nucleic acid molecule comprising one or more nucleic acid sequence that encodes one or more consensus Plasmodium spp. liver stage (LS) immunogen selected from the group consisting of EXP1 (export protein 1), EXP2 (export protein 2), EXP23 (export protein 23), ICP (inhibitor of cysteine protease), TMP21 (transmembrane protein 21), UIS3 (upregulated in infective sporozoites-3), UIS10 (upregulated in infective sporozoites-10), SPECT1 (sporozoite microneme protein essential for cell traversal 1), SPECT2 (sporozoite microneme protein essential for cell traversal 2) and RON2 (rhoptry neck protein 2), wherein the nucleic acid sequence is selected from the group consisting of:
- a) a nucleotide sequence encoding an amino acid sequence selected from the group consisting of SEQ ID NO:
- 1, SEQ ID NO:
- 4, SEQ ID NO:
- 7, SEQ ID NO:
- 10, SEQ ID NO:
- 13, SEQ ID NO:17, SEQ ID NO:
- 20, SEQ ID NO:
- 23, SEQ ID NO:
- 29, SEQ ID NO:
- 32, SEQ ID NO:
- 35, SEQ ID NO:
- 38, and SEQ ID NO:
- 50;
- b) a nucleic acid sequence that encodes an amino acid sequence comprising a fragment comprising at least 90% of the full length of the amino acid sequence selected from the group consisting of SEQ ID NO:
- 1, SEQ ID NO:
- 4, SEQ ID NO:
- 7, SEQ ID NO:
- 10, SEQ ID NO:
- 13, SEQ ID NO:
- 17, SEQ ID NO:
- 20, SEQ ID NO:
- 23, SEQ ID NO:
- 29, SEQ ID NO:
- 32, SEQ ID NO:
- 35, SEQ ID NO:
- 38, and SEQ ID NO:
- 50;
- c) a nucleic acid sequence that encodes the amino acid sequence comprising at least 90% homology to the amino acid sequence selected from the group consisting of SEQ ID NO:
- 1, SEQ ID NO:
- 4, SEQ ID NO:
- 7, SEQ ID NO:
- 10, SEQ ID NO:
- 13, SEQ ID NO:
- 17, SEQ ID NO:
- 20, SEQ ID NO:
- 23, SEQ ID NO:
- 29, SEQ ID NO:
- 32, SEQ ID NO:
- NO:
- 35, SEQ ID NO:
- 38, and SEQ ID NO:
- 50;
- d) the nucleotide sequence selected from the group consisting of SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 5, SEQ ID NO:
- 6, SEQ ID NO:
- 8, SEQ ID NO:
- 9, SEQ ID NO:
- 11, SEQ ID NO:
- 12, SEQ ID NO:
- 14, SEQ ID NO:
- 15, SEQ ID NO:
- 18, SEQ ID NO:
- 19, SEQ ID NO:
- 21, SEQ ID NO:
- 22, SEQ ID NO:
- 24, SEQ ID NO:
- 25, SEQ ID NO:
- 27, SEQ ID NO:
- 28, SEQ ID NO:
- 30, SEQ ID NO:
- 31, SEQ ID NO:
- 33, SEQ ID NO:
- 34, SEQ ID NO:
- 36, SEQ ID NO:
- 37, SEQ ID NO:
- 39, SEQ ID NO:
- 40, SEQ ID NO:
- 42, SEQ ID NO:
- 43, SEQ ID NO:
- 45, SEQ ID NO:
- 46, SEQ ID NO:
- 48, SEQ ID NO:
- 49, SEQ ID NO:
- 51, SEQ ID NO:
- 52, SEQ ID NO:
- 54, and SEQ ID NO:
- 55;
- e) a nucleotide sequence comprising a fragment comprising at least 90% of the full length of the nucleotide sequence selected from the group consisting of SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 5, SEQ ID NO:
- 6, SEQ ID NO:
- 8, SEQ ID NO:
- 9, SEQ ID NO:
- 11, SEQ ID NO:
- 12, SEQ ID NO:
- 14, SEQ ID NO:
- 15, SEQ ID NO:
- 18, SEQ ID NO:
- 19, SEQ ID NO:
- 21, SEQ ID NO:
- 22, SEQ ID NO:
- 24, SEQ ID NO:
- 25, SEQ ID NO:
- 27, SEQ ID NO:
- 28, SEQ ID NO:
- 30, SEQ ID NO:
- 31, SEQ ID NO:
- 33, SEQ ID NO:
- 34, SEQ ID NO:
- 36, SEQ ID NO:
- 37, SEQ ID NO:
- 39, SEQ ID NO:
- 40, SEQ ID NO:
- 42, SEQ ID NO:
- 43, SEQ ID NO:
- 45, SEQ ID NO:
- 46, SEQ ID NO:
- 48, SEQ ID NO:
- 49, SEQ ID NO:
- 51, SEQ ID NO:
- 52, SEQ ID NO:
- 54, and SEQ ID NO:
- 55;
- and
- f) a nucleotide sequence comprising at least 90% identity to the nucleotide sequence selected from the group consisting of SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 5, SEQ ID NO:
- 6, SEQ ID NO:
- 8, SEQ ID NO:
- 9, SEQ ID NO:
- 11, SEQ ID NO:
- 12, SEQ ID NO:
- 14, SEQ ID NO:
- 15, SEQ ID NO:
- 18, SEQ ID NO:
- 19, SEQ ID NO:
- 21, SEQ ID NO:
- 22, SEQ ID NO:
- 24, SEQ ID NO:
- 25, SEQ ID NO:
- 27, SEQ ID NO:
- 28, SEQ ID NO:
- 30, SEQ ID NO:
- 31, SEQ ID NO:
- 33, SEQ ID NO:
- 34, SEQ ID NO:
- 36, SEQ ID NO:
- 37, SEQ ID NO:
- 39, SEQ ID NO:
- 40, SEQ ID NO:
- 42, SEQ ID NO:
- 43, SEQ ID NO:
- 45, SEQ ID NO:
- 46, SEQ ID NO:
- 48, SEQ ID NO:
- 49, SEQ ID NO:
- 51, SEQ ID NO:
- 52, SEQ ID NO:
- 54, and SEQ ID NO:
- 55.
151 more elements
A method of immunizing a mammal against malaria comprising the step of administering an immunogenic composition comprising at least one nucleic acid molecule comprising one or more nucleic acid sequence that encodes one or more consensus Plasmodium spp. liver stage (LS) immunogen selected from the group consisting of:
- EXP1 (export protein 1), EXP2 (export protein 2), EXP23 (export protein 23), ICP (inhibitor of cysteine protease), TMP21 (transmembrane protein 21), UIS3 (upregulated in infective sporozoites-3), UIS10 (upregulated in infective sporozoites-10), SPECT1 (sporozoite microneme protein essential for cell traversal 1), SPECT2 (sporozoite microneme protein essential for cell traversal 2) and RON2 (rhoptry neck protein 2) wherein the nucleic acid sequence is selected from the group consisting of:
- a) a nucleotide sequence encoding the amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:41, SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:38, SEQ ID NO:44, SEQ ID NO:47, SEQ ID NO:50, and SEQ ID NO:53,
- b) a nucleic acid sequence that encodes an amino acid sequence comprising a fragment comprising at least 90% of the full length of the amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:41, SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:38, SEQ ID NO:44, SEQ ID NO:47, SEQ ID NO:50, and SEQ ID NO:53,
- c) a nucleic acid sequence that encodes the amino acid sequence comprising at least 90% homology to the amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:7, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:17, SEQ ID NO:20, SEQ ID NO:23, SEQ ID NO:26, SEQ ID NO:29, SEQ ID NO:41, SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:38, SEQ ID NO:44, SEQ ID NO:47, SEQ ID NO:50, and SEQ ID NO:53:
- d) the nucleotide sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:
- 18, SEQ ID NO:
- 19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:54, and SEQ ID NO:55,
- e) a nucleotide sequence comprising a fragment comprising at least 90% of the full length of the nucleotide sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:
- 18, SEQ ID NO:
- 19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:54, and SEQ ID NO:55, and
- f) a nucleotide sequence comprising at least 90% identity to the nucleotide sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:
- 18, SEQ ID NO:
- 19, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:54, and SEQ ID NO:55 to the tissue of the mammal.
10 more elements
Dependencies are inferred from the claim text.