# US 11,020,473 B2 · Compositions and methods comprising measles virus defective interfering particles for the prevention of infectious diseases > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,020,473 B2 - Document ID: US11020473B2 - Status: Granted - Kind: B2 - Application number: 16/311,457 - Filed: 2017-06-23 - Published: 2019-06-20 - Granted: 2021-06-01 - Earliest claimed: 2016-06-24 - Assignees: Institut Pasteur; Centre National De La Recherche Scientifique; MINISTÈRE DES ARMÉES—Direction Centrale du Service de Sante des Armée - Applicants: Institut Pasteur; Centre National De La Recherche Scientifique; MINISTÈRE DES ARMÉES—Direction Centrale du Service de Santé des Armées - Inventors: Frederic Tangy; Anastassia Komarova; Marie Mura; Chantal Combredet - Web page: https://patentgrep.com/patent/US11020473B2 ## CPC - A61K 39/12: Viral antigens - A61K 39/015: Hemosporidia antigens, e.g. Plasmodium antigens - A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 33/00: Antiparasitic agents - A61K 2039/51: {comprising whole cells, viruses or DNA/RNA} - A61K 2039/5254: {avirulent or attenuated} - A61K 2039/5256: {expressing foreign proteins} - A61K 2039/5258: {Virus-like particles} - A61K 2039/545: {characterised by the dose, timing or administration schedule} - A61K 2039/555: {characterised by a specific combination antigen/adjuvant} - A61K 2039/55588: {Adjuvants of undefined constitution} - A61K 2039/70: {Multivalent vaccine} - C12N 2740/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2740/16234: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2760/18434: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - C12N 2760/18443: viral genome or elements thereof as genetic vector - C12N 2760/18444: Chimeric viral vector comprising heterologous viral elements for production of another viral vector - C12N 2770/36134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract The invention is in the field of prevention or treatment of diseases, in particular infectious diseases, and more particularly in the field of multivalent vaccines. The inventors characterized 5′ copy-back DI-RNAs produced by recombinant MV strains, including rMV-based vaccines and wild-type MV (wt-MV). The efficiency of these DI-RNAs productions in different cell types was compared. For the first time 5′ copy-back DI-RNAs specific binding to RIG-I, MDA5 and LGP2 was assessed and linked to functional outcome in type-I IFN signalling. The inventors provide a composition of products comprising at least (i) a mixture of particles of a rescued recombinant MV-derived virus encoding at least one antigen (ii) a recombinant and/or purified protein, comprising at least one antigen. Regardless of the presentation of the products, and in particular regardless of whether the products are separated or readily separable or presented as a mixture. ## Claims ### Claim 1 A composition of products comprising: a mixture of particles of a rescued recombinant Measles virus (MV) encoding at least one antigen (the “vectored antigen”) or of a rescued modified recombinant MV lacking expression of virulence factors and encoding at least one antigen (the “vectored antigen”), said mixture comprising infectious replicating viral particles and defective interfering (DI) particles; and a protein antigen. ### Claim 2 A composition of products comprising: a mixture of particles of a rescued recombinant MV encoding at least one antigen (the “vectored antigen”) or of a rescued modified recombinant MV lacking expression of virulence factors and encoding at least one antigen (the “vectored antigen”), said mixture comprising infectious replicating viral particles and a defective interfering (DI) genome as DI-RNA in RNA form; and a protein antigen. ### Claim 3 (depends on 1) The composition of claim 1, wherein the rescued recombinant MV particles encode at least one antigen which is not from MV. ### Claim 4 (depends on 1) The composition of claim 1, wherein the vectored antigen and the protein antigen are from at least two distinct infectious species, in particular from two distinct viruses. ### Claim 5 (depends on 1) The composition of claim 1, wherein the vectored antigen and the protein antigen are the same, or wherein at least one vectored antigen is the same as at least one protein antigen. ### Claim 6 (depends on 1) The composition of claim 1, wherein the DI genomes (i.e. the genomes of the DI particles) represent at least 0.00001% of the full-length MV genomic RNA in the composition. ### Claim 7 (depends on 1) The composition of claim 1, wherein at least one vectored antigen and/or protein antigen is from an arbovirus. ### Claim 8 (depends on 7) The composition of claim 7, wherein the arbovirus is selected from the group consisting of Chikungunya Virus (CHIKV), Dengue Virus (DV), West-Nile Virus (WNV), Yellow Fever Virus (YFV), and ZIKA virus (ZV). ### Claim 9 (depends on 1) The composition of claim 1, wherein the at least one vectored antigen and/or protein antigen is from Plasmodium falciparum. ### Claim 10 (depends on 7) The composition of claim 7, wherein the vectored antigens and/or protein antigens are from at least two distinct arboviruses and/or are from at least Plasmodium falciparum and an arbovirus or from Plasmodium falciparum. ### Claim 11 (depends on 10) The composition of claim 10, wherein at least one vectored antigen is from CHIKV and at least one protein antigen is from Plasmodium falciparum, or wherein at least one vectored antigen is from Plasmodium falciparum and at least one protein antigen is from CHIKV. ### Claim 12 (depends on 9) The composition of claim 9, wherein the antigen from Plasmodium falciparum is a CS (circumsporozoite) protein, in particular a recombinant CS protein. ### Claim 13 (depends on 8) The composition of claim 8, wherein the antigen from CHIKV comprises structural proteins of the Chikungunya virus, in particular one or several CHIKV structural proteins E1, E2, E3, C and 6K. ### Claim 14 (depends on 1) The composition of claim 1, wherein the mixture of particles encode at least two distinct vectored antigens. ### Claim 15 (depends on 1) The composition of claim 1, wherein the recombinant MV particles have at least one of the following modifications relatively to the wild-type MV: deletion of the C protein or of a portion thereof; deletion of the V protein or of a portion thereof; duplication of the N gene or of a portion thereof. ### Claim 16 (depends on 1) The composition of claim 1, wherein the recombinant MV particles or the modified recombinant Measles viral particles are obtained from a strain selected from the group consisting of Schwarz, Moraten, Edmonston-Zagreb or from the group consisting of CAM-70, TD 97, Leningrad-16, and Shanghai 191 (Ji-191). ### Claim 17 (depends on 1) A method comprising administering the composition of products according to claim 1 to a patient, wherein said vectored antigen is administered and then said protein antigen is administered later to boost the immune response to said vectored antigen. ### Claim 18 A method of producing modified recombinant MV particles comprising DI particles, comprising the steps of: a) rescuing recombinant MV particles encoding at least one antigen (the “vectored antigen”) or modified MV particles lacking expression of virulence factors and encoding at least one antigen (the “vectored antigen”) from helper cells transfected with cDNA comprising the antigenome of a recombinant MV particle or respectively of a modified recombinant MV particle, wherein said cells express the N, P and L protein of an MV and an RNA polymerase; b) recovering the viral particles from the culture of helper cells, or from a co-culture of helper cells with passage cells, i.e. cells suitable for the passage of the recombinant MV or the modified recombinant MV; c) infecting passage cells with the recombinant MV or the modified recombinant MV, with an MOI of at least 0.09 and in particular at least 0.1 such as a MOI of 0.09 to 1; and d) recovering the recombinant MV particles or the modified recombinant MV particles from the culture of passage cells of c). ### Claim 19 (depends on 1) A viral stock which contains rescued recombinant MV particles or rescued modified recombinant MV particles as defined in claim 1.