IP Library › Granted Patent US 12,280,108
Granted Patent B2
US 12,280,108 · App. 17/231,534 · Granted Apr 22, 2025

Vaccines having an antigen and interleukin-21 as an adjuvant

Inventors: David B. Weiner (Merion, PA); Matthew P. Morrow (Bala Cynwyd, PA)
Assignees: The Trustees of the University of Pennsylvania; Inovio Pharmaceuticals, Inc.
A61K39/39A61K39/08A61K39/12A61K39/21A61K41/0047A61N1/327C07K14/54A61K2039/53A61K2039/55527A61K48/00C12N2740/16134Y02A50/30
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Quick Facts
Patent No.
US 12,280,108
App. No.
17/231,534
Granted
Apr 22, 2025
Kind
B2
Abstract

The invention includes a vaccine comprising an antigen and IL-21. The invention also includes methods for increasing an immune response in a subject. The methods may comprise administering the vaccine to the subject in need thereof.

Claims (22)

1. An immunogenic composition comprising:

a) at least one selected from the group consisting of an antigen and a nucleic acid molecule encoding an antigen,

wherein the antigen is selected from the group consisting of: a human papilloma virus (HPV) antigen or a fragment thereof, an Human Immunodeficiency Virus (HIV) antigen or a fragment thereof, an influenza antigen or a fragment thereof, a Plasmodium falciparum antigen or a fragment thereof, and a C. difficle antigen or a fragment thereof; and

b) a nucleic acid molecule comprising a nucleotide sequence encoding IL-21, wherein IL-21 comprises an amino acid sequence selected from the group consisting of: an amino acid sequence as set forth in SEQ ID NO: 4 and an amino acid sequence that is at least about 90% identical to the entire length of the amino acid sequence as set forth in SEQ ID NO: 4.

2. The immunogenic composition of claim 1 , wherein IL-21 comprises an amino acid sequence selected from the group consisting of: an amino acid sequence as set forth in SEQ ID NO: 4 and an amino acid sequence that is at least about 95% identical to the entire length of the amino acid sequence as set forth in SEQ ID NO: 4.

3. The immunogenic composition of claim 2 , wherein IL-21 comprises an amino acid as set forth in SEQ ID NO: 4.

4. The immunogenic composition of claim 1 , wherein the antigen is encoded by a first nucleic acid and IL-21 is encoded by a second nucleic acid.

5. The immunogenic composition of claim 4 , further comprising an antigen peptide with the same encoded nucleic acid sequence as the antigen of claim 4 , and an IL-21 peptide with the same encoded nucleic acid sequence as IL-21 of claim 4 .

6. The immunogenic composition of claim 4 , wherein the second nucleic acid further comprises an expression vector.

7. The immunogenic composition of claim 1 , wherein the HPV antigen is selected from the group consisting of: HPV16 E6 antigen, HPV16 E7 antigen, and a combination thereof.

8. The immunogenic composition of claim 1 , wherein the HIV antigen is selected from the group consisting of: Env A, Env B, Env C, Env D, B Nef-Rev, Gag, and any combination thereof.

9. The immunogenic composition of claim 1 , wherein the influenza antigen is selected from the group consisting of: H1 HA, H2 HA, H3 HA, H5 HA, BHA antigen, and any combination thereof.

10. The immunogenic composition of claim 1 , wherein the Plasmodium falciparum antigen includes a circumsporozoite (CS) antigen.

11. The immunogenic composition of claim 1 , wherein the C. difficle antigen is selected from the group consisting of: Toxin A, Toxin B, and a combination thereof.

12. The immunogenic composition of claim 1 , further comprising a pharmaceutically acceptable excipient.

13. A method for inducing an immune response in a subject in need thereof, the method comprising administering the immunogenic composition of claim 1 to the subject.

14. The method of claim 13 , wherein administering the immunogenic composition includes electroporation.

15. The method of claim 13 , wherein inducing the immune response in the subject includes inducing a cellular immune response, a humoral immune response, or both a cellular and humoral immune response in subject.

16. A protein comprising one or more amino acid sequences selected from the group consisting of: an amino acid sequence as set forth in SEQ ID NO: 4 and an amino acid sequence that is at least about 90% identical to the entire length of the amino acid sequence as set forth in SEQ ID NO: 4.

17. The protein of claim 16 , wherein the amino acid sequence is selected from the group consisting of: an amino acid sequence as set forth in SEQ ID NO: 4 and an amino acid sequence that is at least about 95% identical to the entire length of the amino acid sequence as set forth in SEQ ID NO: 4.

18. The protein of claim 16 , wherein the amino acid sequence is an amino acid sequence as set forth in SEQ ID NO: 4.

19. A composition comprising one or more proteins of claim 16 .

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 7, 2025
From: WEINER, DAVID B.
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 069772/0781 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 7, 2025
From: MORROW, MATTHEW
To: INOVIO PHARMACEUTICALS, INC.
Reel/Frame 069772/0814 →
Continuity (4)
Continuation 16181594 · Nov 6, 2018
Continuation 15514948
Provisional Application 62058304 · Oct 1, 2014
Related Publication 20210236631A1 · Aug 5, 2021
References Cited (59)
US 20050054726A1 · Thomsen · 2005 [cited by applicant]
US 20050124044A1 · Cunningham · 2005 [cited by applicant]
US 20060034810A1 · Riley · 2006 [cited by examiner]
US 20060269973A1 · Yee · 2006 [cited by applicant]
US 20070041941A1 · Weiner · 2007 [cited by examiner]
US 20070212329A1 · Bruck · 2007 [cited by applicant]
US 20100135958A1 · Hwu · 2010 [cited by examiner]
US 20110002882A1 · Nelson · 2011 [cited by applicant]
US 20120213815A1 · Weiner · 2012 [cited by applicant]
US 20130052222A1 · Weiner · 2013 [cited by applicant]
US 20130195800A1 · Roeth · 2013 [cited by applicant]
US 20130259924A1 · Bancel · 2013 [cited by applicant]
US 20130316366A1 · Yu · 2013 [cited by examiner]
US 20150335726A1 · Weiner · 2015 [cited by examiner]
US 20210052647A1 · Hinrichs · 2021 [cited by examiner]
JP 2011037875A · 2011 [cited by applicant]
WO 0211748A1 · 2002 [cited by applicant]
WO 2003103589 · 2003 [cited by applicant]
WO 2010103038 · 2010 [cited by applicant]
WO 2011119773A1 · 2011 [cited by applicant]
WO 2012040266A2 · 2012 [cited by applicant]
WO 2013151666A3 · 2013 [cited by applicant]
WO WO2013155441A1 · 2013 [cited by examiner]
WO WO2014093894A2 · 2014 [cited by examiner]
WO WO2014150835A1 · 2014 [cited by examiner]
WO WO2015120792A1 · 2015 [cited by examiner]
Fioretti D, Iurescia S, Rinaldi M. Recent advances in design of immunogenic and effective naked DNA vaccines against cancer. Recent Pat Anticancer Drug Discov. Jan. 2014;9(1):66-82. doi: 10.2174/1574891x113089990037. PM… [cited by examiner]
Kumar S, Yan J, Muthumani K, Ramanathan MP, Yoon H, Pavlakis GN, Felber BK, Sidhu M, Boyer JD, Weiner DB. Immunogenicity testing of a novel engineered HIV-1 envelope gp140 DNA vaccine construct. DNA Cell Biol. Jul. 2006… [cited by examiner]
Ig heavy chain epsilon-1 (V-D-J region) [ [cited by examiner]
Parrish-Novak J, et al. Interleukin 21 [ [cited by examiner]
Bolesta E, Kowalczyk A, Wierzbicki A, et al. Increased level and longevity of protective immune responses induced by DNA vaccine expressing the HIV-1 Env glycoprotein when combined with IL-21 and IL-15 gene delivery. J … [cited by applicant]
Cho HJ, Oh BM, Kim JT, Lim J, Park SY, Hwang YS, Baek KE, Kim BY, Choi I, Lee HG. Efficient Interleukin-21 Production by Optimization of Codon and Signal Peptide in Chinese Hamster Ovarian Cells. J Microbial Biotechnol.… [cited by applicant]
Dou et al., “Comparision of Immue Responses Induced in Mice by Vaccination with DNA Vaccine Constructs Expressing Mycobacterial Antigen 85A and Interleukin-21 and Bacillus Galmette-Guerin,” Immunological Investigations,… [cited by applicant]
Dou J, Chen G, Wang J, Zhao F, Chen J, Fang X, Tang Q, Chu L. Preliminary study on mouse interleukin-21 application in tumor gene therapy. Cell Mol Immunol. Dec. 2004; 1(6):461-6. (Year: 2004). [cited by applicant]
Dou J, Tang Q, Zhao F, Chu L, Chen J, Cao M, Liu C, Wang Y, Li Y, Li JL. Comparison of immune responses induced in mice by vaccination with DNA vaccine constructs expressing mycobacterial antigen 85A and interleukin-21 … [cited by applicant]
Feng C, Jin J, Zou Q, Chen X, Zhou C, Wu B, Weiner DB, Wang B. Interleukin-21 inhibits humoral response to an HIV DNA vaccine by enhancing Bcl-6 and Pax-5 expression. Viral Immunol. Apr. 2012;25(2): 131-40. [cited by applicant]
Frohlich A, Marsland BJ, Sonderegger I, Kurrer M, Hodge MR, Harris NL, Kopf M. IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo. Blood. Mar. 1, 2007; 109(5):2023-31. Epub Oct. 31… [cited by applicant]
GenBank: BC066262.1. [cited by applicant]
GenBank: NP _068575.1: interleukin-21 isoform 1 precursor [ [cited by applicant]
He X et al., “Antitumor efficacy 0 viable tumor vaccine modified by heterogenetic ESAT-6 antigen and cytokine IL-21 in melanomatous mouse”, Immunologic Research (2012) 52:240-249. [cited by applicant]
Hu K et al., 2011, “Immunization with DNA vaccine expressing herpes simplex virus type 1 gD and IL-21 protects against mouse herpes keratitis”, Immunological Investigations, 40:265-278. [cited by applicant]
International Search Report and Written Opinion issued in App. No. PCT/US15/52884, mailing date Jan. 6, 2016, 9 pages. [cited by applicant]
Japanese Office Action (with English language translation) for Application No. JP2017-517007, dated Jul. 17, 2019, 8 pages. [cited by applicant]
Kayamuro H, Yoshioka Y, Abe Y, et al. Interleukin-1 family cytokines as mucosal vaccine adjuvants for induction of protective immunity against influenza virus. J Viral. 2010;84(24):12703-12712. [cited by applicant]
Li ZY, Chen J, Petersen E, Zhou DH, Huang SY, Song HQ, Zhu XQ. Synergy of nnIL-21 and nnIL-15 in enhancing DNA vaccine efficacy against acute and chronic Toxoplasma gondii infection in mice. Vaccine. May 23, 2014;32 (25… [cited by applicant]
Lim KL, Jazayeri SD, Yeap SK, Alitheen NB, Bejo MH, Ideris A, Omar AR. Co-administration of avian influenza virus H5 plasmid DNA with chicken IL-15 and IL-18 enhanced chickens immune responses. BMC Vet Res. Aug. 6, 2012… [cited by applicant]
Mauro VP, Chappell Sa. A critical analysis of codon optimization in human therapeutics. Trends Mol Med. Nov. 2014;20(11):604-13. Epub Sep. 25, 2014. [cited by applicant]
Moroz A, Eppolito C, Li Q, Tao J, Clegg CH, Shrikant PA. IL-21 enhances and sustains CDS+ T cell responses to achieve durable tumor immunity: comparative evaluation of IL-2, IL-15, and IL-21. J Immunol. Jul. 15, 2004;17… [cited by applicant]
Muthumani et al., “HIV-1 Env DNA Vaccine plus Protein Boost Delivered by EP Expands B- and T-Cell Responses and Neutralizing Phenotype In Vivo.”, PloS On E, (Dec. 31, 2013), vol. 8, No. 12, p. e84234. [cited by applicant]
Notice of Allowance dated Aug. 6, 2018 for U.S. Appl. No. 15/514,948 (pp. 1-8). [cited by applicant]
Notice of Allowance dated Jan. 19, 2021 for U.S. Appl. No. 16/181,594 (pp. 1-12). [cited by applicant]
Office Action dated Mar. 14, 2018 for U.S. Appl. No. 15/514,948 (pp. 1-5). [cited by applicant]
Office Action dated May 19, 2020 for U.S. Appl. No. 16/181,594 (pp. 1-11). [cited by applicant]
Office Action dated Oct. 23, 2019 for U.S. Appl. No. 16/181,594 (pp. 1-23). [cited by applicant]
Ramanathan et al. “Coimmunization with an optimized IL15 plasmid adjuvant enhances humoral immunity via stimulating B cells induced by genetically engineered DNA vaccines expressing consensus JEV and WNV E Dill”. Vaccin… [cited by applicant]
Skak et al., “Interleukin 21: combination strategies for cancer theapy,” Nature Reviews, Drug Discovery, 7:231-240, 2008. [cited by applicant]
Varkey R, Du Q, Karnell JL, Xiao X, Casey KA, Woods R, Rosenthal K, Wilson S, Dall'Acqua WF, et al. Discovery and characterization of potent IL-21 neutralizing antibodies via a novel alternating antigen immunization and… [cited by applicant]
Yan J, Corbitt N, Pankhong P, Shin T, Khan A, Sardesai NY, Weiner DB. Innnnunogenicity of a novel engineered HIV-1 Glade C synthetic consensus-based envelope DNA vaccine. Vaccine. Sep. 22, 2011;29(41):7173-81. Epub Jun.… [cited by applicant]
Yi JS et al., 2010, “Interleukin-21: A multifunctional regulator of immunity to infections”, Microbes Infect., 12:1111-1119. [cited by applicant]