(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/201377 Al 15 December 2016 (15.12.2016) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 39/00 (2006.01) C12N 9/52 (2006.01) kind of national protection available): AE, AG, AL, AM, C07K 14/31 (2006.01) G01N 33/569 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) International Application Number: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US20 16/037095 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, 10 June 2016 (10.06.2016) MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (25) Filing Language: English SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (26) Publication Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 62/173,783 10 June 2015 (10.06.2015) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (71) Applicant: MODERNA THERAPEUTICS, INC. TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, [US/US]; 200 Technology Square, Cambridge, Massachu TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, setts 02139 (US). DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, (72) Inventors; and SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, (71) Applicants : YI-CHUN HUANG, Eric [US/US]; 90 GW, KM, ML, MR, NE, SN, TD, TG). Wareham Street, Unit 302, Boston, Massachusetts 02 118 (US). HOGE, Stephen [US/US]; 66 Summit Ave, Brook- Published: line, Massachusetts 02446 (US). — with international search report (Art. 21(3)) (74) Agents: LAHERTY, Carol D. et al; Cooley LLP, 1299 — with sequence listing part of description (Rule 5.2(a)) Pennsylvania Avenue, NW, Suite 700, Washington, Dis trict of Columbia 20004 (US). (54) Title: TARGETED ADAPTIVE VACCINES o- , :; v - (57) Abstract: The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynuc - leotide molecules encoding targeted adaptive vaccines (TAVs), such as PCSK9 TAVs, TNF alpha TAVs, IL-17A TAVs, or GDF8 TAVs. O TARGETED ADAPTIVE VACCINES CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. Provisional Application No. 62/173,783, filed on June 10, 2015; which is incorporated by reference herein in its entirety. STATEMENT REGARDING SEQUENCE LISTIN [0002] The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing is MRNA_012_01WO_ST25.txt. The text file is 1,333 KB, was created on June 10, 2016, and is being submitted electronically via EFS-Web. FIELD OF THE INVENTION [0003] The present invention relates to compositions, methods, processes, kits and devices for the design, preparation, manufacture, formulation and use of polynucleotides encoding targeted adaptive vaccines (TAVs). BACKGROUND OF THE INVENTION [0004] Vaccination is an effective way to provide prophylactic protection against infectious diseases, such as influenza, AIDS, hepatotisis virus infection, cholera, malaria and tuberculosis, and many other diseases. Vaccines may also be used to treat diseases, such as cancers. For example, the first cancer treatment vaccine, sipuleucel- T (Provenge®, manufactured by Dendreon) is used for certain men with metastatic prostate cancer. It is designed to stimulate an immune response to prostatic acid phosphatase (PAP), an antigen that is found on most prostate cancer cells. (Kantoff PW, et al, 2010, New England Journal of Medicine, 365, 411-422, which is incorporated herein by reference in its entirety). [0005] A typical vaccine contains an antigenic target molecule, e.g., an agent that resembles a weakened or dead form of the disease-causing agent, which could be a microorganism, such as bacteria, virus, fungi, parasite and prion, or the toxins or one or more surface proteins (often called antigens) of such a microorganism. The antigenic target molecule may alternatively be an endogenous polypeptide, e.g., an antigenic polypeptide or fragment thereof expressed or cancer cells or associated with a disease. The antigen or agent in the vaccine can stimulate the body's immune system to recognize the agent as a foreign invader, generate antibodies against it, destroy it and develop a memory of it. The vaccine-induced memory enables the immune system to act quickly to protect the body from any of these agents that it later encounters. [0006] Vaccine production used in the art has several stages, including the generation of antigens, antigen purification and inactivation, and vaccine formulation. First, the antigen is generated through culturing viruses in cell lines, growing bacteria in bioreactors, or producing recombinant proteins derived from viruses and bacteria in cell cultures, yeast or bacteria. Recombinant proteins are then purified and the viruses and bacteria are inactivated before they are formulated with adjuvants in vaccines. It has been a challenge to drastically reduce the time and expense associated with current technologies in vaccine development. [0007] It is of great interest to develop new approaches for developing new vaccines, not only for infectious agents and cancer but for other therapeutic indications. SUMMARY OF THE INVENTION [0008] Described herein are compositions, methods, processes, kits and devices for the design, preparation, manufacture and/or formulation of polynucleotides encoding targeted adaptive vaccines (TAVs). [0009] In one embodiment, the present invention comprises an mRNA comprising: (a) a first region comprising a sequence encoding one or more polypeptide (e.g., an immunogenic polypeptide); and, optionally, (b) a second region comprising a sequence encoding one or more immunomodulatory polypeptide, wherein the mRNA comprises a modified nucleobase. In particular embodiments, the mRNA comprises the second region. In particular embodiments, the mRNA further comprises a third region between the first region and the second region, wherein the third region comprises a sequence encoding a spacer or a cleavage site. In certain embodiments, the spacer or cleavage site is a 2A peptide or a cathepsin S cleavage site. In particular embodiments, first region comprises two or more sequences encoding polypeptides, which may comprise the same or different amino acid sequences. In particular embodiments, the first region further comprises a sequence encoding a linker or a cleavage site between the sequences encoding the two or more polypeptides. In certain embodiments, the linker or cleavage site is a 2A peptide or a cathepsin cleavage site. In particular embodiments, the one or more polypeptide comprises a human or murine polypeptide or fragment or variant thereof. In particular embodiments, the one or more polypeptides is proprotein convertase subtilisin/kexin type 9 (PCSK9), interleukin-17A (IL-17A), tumor necrosis factor alpha (TNF alpha) or growth differentiation factor 8 (GDF8). [00010] In particular embodiments, the second region of the mRNA comprises two or more sequences encoding immunomodulatory polypeptides, which may be the same or different. In some embodiments, the second region further comprises a sequence encoding a linker or a cleavage site between the sequences encoding the two or more immunomodulatory polypeptides. [00011] In particular embodiments, the linker or cleavage site is a 2A peptide or a cathepsin cleavage site. In certain embodiments, the immunomodulatory polypeptide is selected from the group consisting of: GM-CSF, IL2, IL12, IL15, IL21, IL23, soluble LAG3, agonist CD28, anti-PD1, anti-PDL1/2, anti-OX40/OX40L, anti- GITR/GITRL, and anti-TIM3. In particular embodiments, the one or more immunomodulatory polypeptide is an immune enhancing polypeptide. In particular embodiments, the immune enhancing polypeptide is selected from the group consisting of: mannose binding protein, flagellin derived immunogens, T cell epitopes from Tetanus toxin, T cell epitope of M2 protein of H1N1 Puerto Rico/8, epitope from influenza HA antigen, universal T helper epitope, and a chimeric MHC class II peptide with epitopes from tetanus toxoid and diphtheria toxoid. In particular embodiments, the immune enhancing polypeptide is T cell epitope of M2 protein of H1N1 Puerto Rico/8 or mannose binding protein. In certain embodiments, the mRNA encodes a fusion polypeptide comprising a scaffold polypeptide, the first region, and the second region, wherein the first region and the second region are inserted into the scaffold polypeptide. In certain embodiments, the mRNA further comprises a fourth region comprising a sequence encoding a dendritic cell targeting polypeptide. In particular embodiments, the dendritic cell targeting polypeptide is selected from the group consisting of a polypeptide encoding an antibody, a polypeptide encoding an antibody fragment, and a peptide that targets one or more dendritic cell surface markers. In certain embodiments, the dendritic cell surface marker is selected