WO2017100759A1 - Recombinant respiratory syncytial virus strains with mutations in the m2-2 orf providing a range of attenuation phenotypes - Google Patents

Recombinant respiratory syncytial virus strains with mutations in the m2-2 orf providing a range of attenuation phenotypes Download PDF

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Publication number
WO2017100759A1
WO2017100759A1 PCT/US2016/066146 US2016066146W WO2017100759A1 WO 2017100759 A1 WO2017100759 A1 WO 2017100759A1 US 2016066146 W US2016066146 W US 2016066146W WO 2017100759 A1 WO2017100759 A1 WO 2017100759A1
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rsv
seq
mutations
recombinant rsv
genome
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PCT/US2016/066146
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English (en)
French (fr)
Inventor
Peter L. Collins
Ursula J. Buchholz
Cindy LUONGO
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US Department of Health and Human Services
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US Department of Health and Human Services
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Priority to JP2018530548A priority Critical patent/JP7079197B2/ja
Priority to EP16822321.2A priority patent/EP3386539A1/en
Priority to CA3007408A priority patent/CA3007408A1/en
Priority to CN201680081646.4A priority patent/CN109310752B/zh
Priority to BR112018011674-2A priority patent/BR112018011674A2/pt
Priority to RU2018125246A priority patent/RU2773746C2/ru
Priority to AU2016366771A priority patent/AU2016366771B2/en
Priority to KR1020187019759A priority patent/KR102854980B1/ko
Application filed by US Department of Health and Human Services filed Critical US Department of Health and Human Services
Priority to KR1020257029082A priority patent/KR20250134719A/ko
Priority to US16/061,314 priority patent/US10655109B2/en
Publication of WO2017100759A1 publication Critical patent/WO2017100759A1/en
Anticipated expiration legal-status Critical
Priority to US16/877,277 priority patent/US11332721B2/en
Priority to JP2022030778A priority patent/JP7357709B2/ja
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A61K39/155—Paramyxoviridae, e.g. parainfluenza virus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
    • A61K2039/522—Bacterial cells; Fungal cells; Protozoal cells avirulent or attenuated
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5254—Virus avirulent or attenuated
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A61K2039/541—Mucosal route
    • A61K2039/543—Mucosal route intranasal
    • C—CHEMISTRY; METALLURGY
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    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
    • C12N2760/18521—Viruses as such, e.g. new isolates, mutants or their genomic sequences
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
    • C12N2760/18522—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
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    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
    • C12N2760/18534—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
    • C12N2760/18561—Methods of inactivation or attenuation
    • C12N2760/18562—Methods of inactivation or attenuation by genetic engineering

Definitions

  • the one or more modifications to the genome of the recombinant RSV further comprise nucleotide mutations encoding amino acid substitution K51R in the NS2 protein of the RSV ("NS2"). In some embodiments, the one or more modifications to the genome of the recombinant RSV further comprise nucleotide mutations encoding amino acid substitution T24A in the N protein of the RSV ("N"). In some embodiments, the one or more modifications to the genome of the recombinant RSV further comprise nucleotide mutations encoding amino acid substitution K51R in the NS2 protein and T24A in the N protein of the RSV ("NS2/N").
  • the genome of the recombinant RSV comprises the 6120, ⁇ 2-2, and 1030s mutations, and a nucleotide sequence corresponding to a positive-sense sequence at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 16 (LID/AM2- 2/1030s sequence).
  • the genome of the recombinant RSV comprises the 6120, cp, and ⁇ 2-2 mutations, and a nucleotide sequence corresponding to a positive-sense sequence at least 90% (such as at least 95% or at least 99%) identical to SEQ ID NO: 17 (LID/cp/AM2-2 sequence).
  • FIG. 5 Schematic diagrams of the genomes of four examples of derivatives of RSV LID/AM2-2 that each contains one or more additional attenuating mutations.
  • the "LID” backbone is a D46-based genome containing the "6120" mutation.
  • the ⁇ 2-2 mutation and the 6120 mutation are indicated.
  • the other attenuating mutations include the set of "cp” mutations (five amino acid substitutions in the N, F, and L proteins: N (V267I), F (E218A and T523I), and L (C319Y and H1690Y)), deletion of the SH gene (see FIG. 6), and the "1030s" mutation in the L protein. Note that viruses from which the entire SH gene has been deleted (RSV ASH/AM2-2 and RSV cp/ASH/AM2-2) are not referred to as "LID" because the SH deletion removes the 6120 mutation.
  • FIGs. 9A and 9B Peak titers of exemplary recombinant RSV in seronegative infants and children. Peak titers of RSV MEDIMM2-2 and RSV rA2cp248/404/1030ASH (FIG. 9A) or RSV LID/AM2-2 (FIG. 9B) in nasal washes of seronegative infants and children (6-24 months of age) following a single IN inoculation are shown. The results for RSV MEDI/AM2-2 and
  • SEQ ID NO: 11 is an exemplary polynucleotide sequence encoding F001BB.
  • deletion or other mutations of the SH, NS2, or NS 1 genes, or parts of their ORFs may be combined with a disclosed M2-2 mutation (such as a ⁇ 2-2, AM2-2-Acll, or AM2-2-Hin(MI mutation).
  • the recombinant strains may comprise one or more changes in the SH protein, including an ablation or elimination of the SH protein.
  • the viral strains comprise a deletion in the SH gene.
  • the viral strains comprise a 419 nucleotide deletion at position 4197-4615 (4198-4616 of SEQ ID NO: 1), denoted herein as the "ASH" mutation.
  • the recombinant RSV strain comprises a genome comprising the NS2, N, and ⁇ 2-2- ⁇ : ⁇ mutations as described herein, the following nucleotide mutations with positions relative to SEQ ID NO: 1 : 404C, 779G, deletion of C1099, 1139A, 1140G, 1182G, 1210G, 5612A, 5616A, 5640G, 6216C, 6222C, 6387T, 7215C, 7482T, 7560 A, 7702G, 10515T, and 13634A; and a nucleotide sequence corresponding to an antigenomic cDNA sequence at least 90% identical, at least 95% identical, and/or at least 99% identical to SEQ ID NO: 19 (276 sequence).
  • Counterpart domains and their encoding gene segments embrace an assemblage of species having a range of size and amino acid (or nucleotide) sequence variations, which range is defined by a common biological activity among the domain or gene segment variants.
  • two selected protein domains encoded by counterpart gene segments within the invention may share substantially the same qualitative activity, such as providing a membrane spanning function, a specific binding activity, an immunological recognition site, etc.
  • a specific biological activity shared between counterparts e.g., between selected protein segments or proteins, will be substantially similar in quantitative terms, i.e. , they will not vary in respective quantitative activity profiles by more than 30%, preferably by no more than 20%, more preferably by no more than 5-10%.
  • immune responses can be detected by assay of cytokines in nasal washes or sera, ELISPOT of immune cells from either source, quantitative RT-PCR or microarray analysis of nasal wash or serum samples, and restimulation of immune cells from nasal washes or serum by re-exposure to viral antigen in vitro and analysis for the production or display of cytokines, surface markers, or other immune correlates measured by flow cytometry or for cytotoxic activity against indicator target cells displaying RSV antigens.
  • individuals are also monitored for signs and symptoms of upper respiratory illness.
  • RSV respiratory syncytial virus
  • Clause 17 A pharmaceutical composition comprising an immunologically effective amount of the recombinant RSV variant encoded by the isolated polynucleotide molecule of any one of clauses 1- 13.
  • Antigenomic cDNA sequence of LID/AM2-2 (SEQ ID NO: 5)
  • the same four AM2-2-containing viruses were investigated for replication in the respiratory tract of AGMs, namely: RSV LID/AM2-2, RSV ASH/AM2-2, RSV LID/AM2-2/1030s, and RSV
  • AGMs in groups of four were inoculated by the combined IN and IT routes with 6 logio PFU per ml per each of the two sites (IN and IT).
  • NP swabs were taken daily on days 1-10 and 12, and tracheal lavages were taken on days 2, 4, 6, 8, 10, and 12 (Tables 1 and 2). This showed that all three viruses that contained one or more additional attenuating mutations were more attenuated than RSV LID/AM2-2. In particular, the RSV AM2-2/1030s virus appeared to be the most attenuated.
  • RSV 6120/G/FBBcpHEKMM2-2 contains the native A2 G gene and codon- optimized A2F gene (FBB) that also has the two HEK mutations, K66E and Q101P and the two cp mutations contained in the F gene, namely E218A and T523I.
  • This example illustrates evaluation of additional RSV ⁇ 2-2 constructs.
  • D46 is a second, recombinantly-derived version of strain A2 that differs in nucleotide length due to a single nucleotide insert at position 1099 (as indicated), resulting in a genome nucleotide length of 15,223. This insertion was removed in RSV 276 and the assignment at that position became T.

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PCT/US2016/066146 2015-12-11 2016-12-12 Recombinant respiratory syncytial virus strains with mutations in the m2-2 orf providing a range of attenuation phenotypes Ceased WO2017100759A1 (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
AU2016366771A AU2016366771B2 (en) 2015-12-11 2016-12-12 Recombinant respiratory syncytial virus strains with mutations in the M2-2 ORF providing a range of attenuation phenotypes
CA3007408A CA3007408A1 (en) 2015-12-11 2016-12-12 Recombinant respiratory syncytial virus strains with mutations in the m2-2 orf providing a range of attenuation phenotypes
CN201680081646.4A CN109310752B (zh) 2015-12-11 2016-12-12 提供一系列减毒表型的在m2-2 orf中具有突变的重组呼吸道合胞病毒株
BR112018011674-2A BR112018011674A2 (pt) 2015-12-11 2016-12-12 cepas do vírus sincicial respiratório recombinante com mutações na orf de m2-2 fornecendo uma faixa de fenótipos de atenuação
RU2018125246A RU2773746C2 (ru) 2015-12-11 2016-12-12 Рекомбинантные штаммы респираторно-синцитиального вируса с мутациями в м2-2 orf, обеспечивающими диапазон аттенуирующих фенотипов
KR1020187019759A KR102854980B1 (ko) 2015-12-11 2016-12-12 약독화 표현형의 범위를 제공하는 m2-2 orf 변이를 가지는 재조합 호흡기 세포융합 바이러스 균주
KR1020257029082A KR20250134719A (ko) 2015-12-11 2016-12-12 약독화 표현형의 범위를 제공하는 m2-2 orf 변이를 가지는 재조합 호흡기 세포융합 바이러스 균주
JP2018530548A JP7079197B2 (ja) 2015-12-11 2016-12-12 さまざまな弱毒化表現型をもたらすｍ２－２ ｏｒｆにおける突然変異を含む組換えｒｓウイルス株
EP16822321.2A EP3386539A1 (en) 2015-12-11 2016-12-12 Recombinant respiratory syncytial virus strains with mutations in the m2-2 orf providing a range of attenuation phenotypes
US16/061,314 US10655109B2 (en) 2015-12-11 2016-12-12 Recombinant respiratory syncytial virus stains with mutations in the M2-2 ORF providing a range of attenuation phenotypes
US16/877,277 US11332721B2 (en) 2015-12-11 2020-05-18 Recombinant respiratory syncytial virus strains with mutations in the M2-2 ORF providing a range of attenuation phenotypes
JP2022030778A JP7357709B2 (ja) 2015-12-11 2022-03-01 さまざまな弱毒化表現型をもたらすｍ２－２ ｏｒｆにおける突然変異を含む組換えｒｓウイルス株

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US201562266199P 2015-12-11 2015-12-11
US62/266,199 2015-12-11

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US16/061,314 A-371-Of-International US10655109B2 (en) 2015-12-11 2016-12-12 Recombinant respiratory syncytial virus stains with mutations in the M2-2 ORF providing a range of attenuation phenotypes
US16/877,277 Continuation US11332721B2 (en) 2015-12-11 2020-05-18 Recombinant respiratory syncytial virus strains with mutations in the M2-2 ORF providing a range of attenuation phenotypes

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US (2) US10655109B2 (enExample)
EP (1) EP3386539A1 (enExample)
JP (2) JP7079197B2 (enExample)
KR (2) KR20250134719A (enExample)
CN (1) CN109310752B (enExample)
AR (1) AR106956A1 (enExample)
AU (1) AU2016366771B2 (enExample)
BR (1) BR112018011674A2 (enExample)
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021248086A3 (en) * 2020-06-05 2022-01-13 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Live attenuated respiratory syncytial virus
US11273214B2 (en) * 2017-05-29 2022-03-15 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Recombinant chimeric bovine/human parainfluenza virus 3 expressing RSV G and its use
WO2025106787A1 (en) 2023-11-17 2025-05-22 Sanofi Pasteur Inc. Trehalose vaccine formulation

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4757597A (en) 1982-06-30 1988-07-19 Luk Lamellen Und Kupplungsbau Gmbh Method of assembling a friction clutch
WO2002044334A2 (en) * 2000-11-28 2002-06-06 Aviron, Inc. Recombinant rsv virus expression systems and vaccines
US20040005542A1 (en) * 2001-06-22 2004-01-08 Krempl Christine D Respiratory syncytial virus vaccines expressing protective antigens from promotor- proximal genes
US6790449B2 (en) 1995-09-27 2004-09-14 The United States Of America As Represented By The Department Of Health And Human Services Methods for producing self-replicating infectious RSV particles comprising recombinant RSV genomes or antigenomes and the N, P, L, and M2 proteins
US20150118732A1 (en) * 2012-04-13 2015-04-30 The United States Of America, As Rep. By The Sec. Dept. Of Health And Human Services Genetically stable live attenuated respiratory syncytial virus vaccine and its production

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7465574B2 (en) 1994-09-30 2008-12-16 Medimmune, Llc Recombinant RSV virus expression systems and vaccines
US6713066B1 (en) 1996-07-15 2004-03-30 The United States Of America As Represented By The Department Of Health And Human Services Production of attenuated respiratory syncytial virus vaccines involving modification of M2 ORF2
DE10118446A1 (de) 2001-04-12 2002-10-17 Thomas Hartung Prüfverfahren zur Untersuchung fließfähiger Medien auf Gehalte an mikrobiellen Toxinen
US20160228536A1 (en) * 2013-09-18 2016-08-11 Medimmune, Llc Recombinant respiratory syncytial virus (rsv) and vaccines
WO2017030997A1 (en) 2015-08-14 2017-02-23 Research Institute At Nationwide Children's Hospital Respiratory syncytial virus having altered ns1 protein function and related materials and methods

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4757597A (en) 1982-06-30 1988-07-19 Luk Lamellen Und Kupplungsbau Gmbh Method of assembling a friction clutch
US6790449B2 (en) 1995-09-27 2004-09-14 The United States Of America As Represented By The Department Of Health And Human Services Methods for producing self-replicating infectious RSV particles comprising recombinant RSV genomes or antigenomes and the N, P, L, and M2 proteins
WO2002044334A2 (en) * 2000-11-28 2002-06-06 Aviron, Inc. Recombinant rsv virus expression systems and vaccines
US20040005542A1 (en) * 2001-06-22 2004-01-08 Krempl Christine D Respiratory syncytial virus vaccines expressing protective antigens from promotor- proximal genes
US20150118732A1 (en) * 2012-04-13 2015-04-30 The United States Of America, As Rep. By The Sec. Dept. Of Health And Human Services Genetically stable live attenuated respiratory syncytial virus vaccine and its production

Non-Patent Citations (56)

* Cited by examiner, † Cited by third party
Title
BELSHE ET AL., J. MED. VIROLOGY, vol. 1, 1977, pages 157 - 162
BERMINGHAM ALISON ET AL: "The M2-2 protein of human respiratory syncytial virus is a regulatory factor involved in the balance between RNA replication and transcription", PROCEEDINGS NATIONAL ACADEMY OF SCIENCES PNAS, NATIONAL ACADEMY OF SCIENCES, US, vol. 96, no. 20, 28 September 1999 (1999-09-28), pages 11259 - 11264, XP002154525, ISSN: 0027-8424, DOI: 10.1073/PNAS.96.20.11259 *
BERMINGHAM; COLLINS, PROC NATL ACAD SCI USA, vol. 96, 1999, pages 11259 - 11264
BUKREYEV A ET AL: "Granulocyte-macrophage colony-stimulating factor expressed by recombinant respiratory syncytial virus attenuates viral replication and increases the level of pulmonary antigen-presenting cells", JOURNAL OF VIROLOGY, THE AMERICAN SOCIETY FOR MICROBIOLOGY, US, vol. 75, no. 24, 1 December 2001 (2001-12-01), pages 12128 - 12140, XP002335337, ISSN: 0022-538X, DOI: 10.1128/JVI.75.24.12128-12140.2001 *
BUKREYEV ET AL., J VIROL, vol. 71, 1997, pages 8973 - 8982
BUKREYEV ET AL., J VIROL, vol. 75, 2001, pages 12128 - 12140
BUKREYEV; MURPHY; COLLINS, J VIROL, vol. 74, 2000, pages 11017 - 11026
C. LUONGO ET AL: "Increased Genetic and Phenotypic Stability of a Promising Live-Attenuated Respiratory Syncytial Virus Vaccine Candidate by Reverse Genetics", JOURNAL OF VIROLOGY, vol. 86, no. 19, 1 October 2012 (2012-10-01), pages 10792 - 10804, XP055066275, ISSN: 0022-538X, DOI: 10.1128/JVI.01227-12 *
CHIRKOVA ET AL., J VIROL, vol. 87, 2013, pages 13466 - 13479
COLLINS ET AL., ADV VIRUS RES, vol. 54, 1999, pages 423 - 451
COLLINS ET AL., PNAS, vol. 92, 1995, pages 11563 - 11567
COLLINS ET AL., PROC NATL ACAD SCI USA, vol. 92, 1995, pages 11563 - 11567
COLLINS ET AL., PROC. NATL. ACAD. SCI. USA, vol. 83, 1986, pages 4594 - 4598
COLLINS ET AL., PROC. NATL. ACAD. SCI. USA, vol. 84, 1987, pages 5134 - 5138
COLLINS; GRAHAM, J VIROL, vol. 82, 2008, pages 2040 - 2055
COLLINS; KARRON: "Fields Virology", 2013, pages: 1086 - 1123
CONNORS ET AL., VIROLOGY, vol. 208, 1995, pages 478 - 484
DEVINCENZO ET AL., AM J RESPIR CRIT CARE MED, vol. 182, 2010, pages 1305 - 1314
DURBIN ET AL., VIROLOGY, vol. 235, no. 2, 1997, pages 323 - 332
EL SALEEBY ET AL., J INFECT DIS, vol. 204, 2011, pages 996 - 1002
FIRESTONE ET AL., VIROLOGY, vol. 225, 1996, pages 419 - 422
FRIEDEWALD ET AL., J. AMER. MED. ASSOC., vol. 204, 1968, pages 690 - 694
GHARPURE ET AL., J. VIROL., vol. 3, 1969, pages 414 - 421
HOFFMAN ET AL., J. VIROL, vol. 71, 1997, pages 4272 - 4277
JIN ET AL., J VIROL, vol. 74, 2000, pages 74 - 82
JIN H ET AL: "Respiratory Syncytial Virus That Lacks Open Reading Frame 2 of the M2 Gene (M2-2) Has Altered Growth Characteristics and Is Attenuated in Rodents", JOURNAL OF VIROLOGY, THE AMERICAN SOCIETY FOR MICROBIOLOGY, US, vol. 74, no. 1, 1 January 2000 (2000-01-01), pages 74 - 82, XP002302691, ISSN: 0022-538X *
JUHASZ ET AL., VACCINE, vol. 17, 1999, pages 1416 - 1424
KARRON ET AL., J INFECT DIS, vol. 176, 1997, pages 1428 - 1436
KARRON ET AL., J INFECT DIS, vol. 191, 2005, pages 1093 - 1104
KARRON ET AL., JID, vol. 191, 2005, pages 1093 - 1104
KARRON ET AL., PROC. NATL. ACAD. SCI. USA, vol. 94, 1997, pages 13961 - 13966
KARRON ET AL., SCIENCE TRANSL MED, vol. 7, no. 312, 2015, pages 312RAL75
KARRON RUTH A ET AL: "Live-attenuated respiratory syncytial virus vaccines", 1 January 2013, CHALLENGES AND OPPORTUNITIES FOR RESPIRATORY SYNCYTIAL VIRUS VACCINES IN: CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY; ISSN 0070-217X; VOL. 372; [CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY; ISSN 0070-217X; VOL. 372], SPRINGER BERLIN HEIDELBERG,, ISBN: 978-3-642-38918-4, XP009192925 *
KARRON; BUCHHOLZ; COLLINS, CURR TOP MICROBIOL IMMUNOL, vol. 372, 2013, pages 259 - 284
KATO ET AL., EMBO. J., vol. 16, 1997, pages 578 - 587
KREMPL ET AL., J VIROL, vol. 76, 2002, pages 11931 - 11942
LAWLOR; SCHICKLI; TANG, J GEN VIROL, vol. 94, 2013, pages 2627 - 2635
LIANG ET AL., J VIROL, vol. 88, 2014, pages 4237 - 4250
LIANG ET AL., J VIROL, vol. 89, 2015, pages 9499 - 9510
LUONGO ET AL., J VIROL, vol. 86, 2012, pages 10792 - 10804
LUONGO ET AL., J VIROL, vol. 87, 2013, pages 1985 - 1996
LUONGO ET AL., VACCINE, vol. 27, 2009, pages 5667 - 5676
MALKIN ET AL., PLOS ONE, vol. 8, 2013, pages E77104
MCLELLAN ET AL., SCIENCE, vol. 340, no. 6136, 2013, pages 1113 - 1117
R. A. KARRON ET AL: "A gene deletion that up-regulates viral gene expression yields an attenuated RSV vaccine with improved antibody responses in children", SCIENCE TRANSLATIONAL MEDICINE, vol. 7, no. 312, 4 November 2015 (2015-11-04), pages 312ra175 - 312ra175, XP055354701, ISSN: 1946-6234, DOI: 10.1126/scitranslmed.aac8463 *
SAKURAI ET AL., J VIROL, vol. 73, 1999, pages 2956 - 2962
SCIENCE, vol. 342, no. 6158, 2013, pages 592 - 598
SKIADOPOULOS ET AL., VIROLOGY, vol. 272, 2000, pages 225 - 234
TENG ET AL., J VIROL, vol. 74, 2000, pages 9317 - 9321
WHITEHEAD ET AL., J VIROL, vol. 72, 1998, pages 4467 - 4471
WHITEHEAD ET AL., J VIROL, vol. 72, 1999, pages 4467 - 4471
WHITEHEAD ET AL., J VIROL, vol. 73, 1999, pages 3438 - 3442
WHITEHEAD ET AL., J VIROL, vol. 73, 1999, pages 871 - 877
WHITEHEAD ET AL., VIROLOGY, vol. 247, 1998, pages 232 - 239
WHITHEAD ET AL: "Recombinant Respiratory Syncytial Virus (RSV) Bearing a Set of Mutations from Cold-Passaged RSV Is Attenuated in Chimpanzees", JOURNAL OF VIROLOGY, vol. 72, no. 5, 1 January 1998 (1998-01-01), pages 4467 - 4471, XP055147381 *
WRIGHT ET AL., ARCH. GES. VIRUSFORSCH., vol. 41, 1973, pages 238 - 247

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