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Human Respiratory Syncytial Virus

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
  2. Vaccine Related Pathogen Genes
    1. N protein (Defense factor)
    2. P protein (Other)
    3. F protein (Protective antigen)
    4. G (Protective antigen)
    5. HN (Protective antigen)
    6. L protein (Protective antigen)
    7. M2-1 (Protective antigen)
    8. NS1 Protein (Protective antigen)
    9. NS2 (Protective antigen)
    10. RSV Prefusion F protein based (Protective antigen)
    11. SH (Protective antigen)
    12. M protein (Virmugen)
    13. M2-2 (Virmugen)
    14. RSV strain A2 (Virmugen)
  3. Vaccine Information
    1. (rBCG-N-hRSV) Recombinant Mycobacterium bovis BCG vaccine
    2. Ad26/protein preF RSV Vaccine Coadministered With an Influenza Vaccine
    3. Ad5-RSV-F
    4. D46/NS2/N/ΔM2-2-HindIII
    5. HDAd-sFsyn
    6. HRSV DNA vaccine DRF-412
    7. HRSV DNA vaccine pND-G
    8. Human Respiratory Syncytial Virus M2-2 mutant vaccine
    9. LID/ΔM2-2/1030s
    10. MEDI-534
    11. Mnull RSV
    12. MVA - RSV
    13. rB-HPIV3-F1
    14. rB-HPIV3-G1
    15. rB/HPIV3- RSV-F
    16. rBPIV3-RSV-G
    17. Respiratory syncytal virus bivalent prefusion F vaccine
    18. rPIV3-RSV-hMPV
    19. RSV/ΔNS2/Δ1313/I1314
    20. rVSV-Gstem-RSV-F
    21. VSV-RSV(F/G)
  4. References
I. General Information
1. NCBI Taxonomy ID:
11250
2. Disease:
Respiratory tract disease
3. Introduction
Human Respiratory Syncytial Virus consists of two antigenic subtypes, A and B. Subtype B is more common and is considered the asymptomatic strain. More severe outbreaks are attributed to subtype A. The severity of the disease ranges from mild to life-threatening. It can cause mortality or morbidity in the elderly or immunosuppressed individuals. It is the most common pathogen leading to hospitalization in young children (Wiki: Human respiratory syncytial virus).
1. F protein
2. G
  • Gene Name : G
  • Sequence Strain (Species/Organism) : Human respiratory syncytial virus A strain Long
  • NCBI Protein GI : 1353203
  • Other Database IDs : CDD:144411
    CDD:224196
  • Taxonomy ID : 11260
  • Gene Strand (Orientation) : ?
  • Protein Name : Major surface glycoprotein G
  • Protein pI : 10.72
  • Protein Weight : 34785.98
  • Protein Length : 465
  • Protein Note : Attachment glycoprotein G; Membrane-bound glycoprotein; mG
  • Protein Sequence : Show Sequence
    >sp|P20895.2|GLYC_HRSVL RecName: Full=Major surface glycoprotein G; AltName: Full=Attachment glycoprotein G; AltName: Full=Membrane-bound glycoprotein; Short=mG
    MSKNKDQRTAKTLEKTWDTLNHLLFISSGLYKLNLKSIAQITLSILAMIISTSLIITAIIFIASANHKVT
    LTTAIIQDATSQIKNTTPTYLTQDPQLGISFSNLSEITSQTTTILASTTPGVKSNLQPTTVKTKNTTTTQ
    TQPSKPTTKQRQNKPPNKPNNDFHFEVFNFVPCSICSNNPTCWAICKRIPNKKPGKKTTTKPTKKPTFKT
    TKKDHKPQTTKPKEVPTTKPTEEPTINTTKTNIITTLLTNNTTGNPKLTSQMETFHSTSSEGNLSPSQVS
    TTSEHPSQPSSPPNTTRQ
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (Tripp et al., 2018)The G protein modulates neonatal regulatory B lymphocytes (nBreg cells) to produce immunosuppressive interleukin-10 (IL-10).
  • Related Vaccine(s): HRSV DNA vaccine pND-G , MVA - RSV , rB-HPIV3-F1 , rB-HPIV3-G1 , rBPIV3-RSV-G , rVSV-Gstem-RSV-F , VSV-RSV(F/G)
3. HN
  • Gene Name : HN
  • Sequence Strain (Species/Organism) : Human respirovirus 1
  • NCBI Gene ID : 935266
  • NCBI Protein GI : 19718372
  • Locus Tag : Hpv1gp09
  • Protein Accession : NP_604441
  • Taxonomy ID : 12730
  • Gene Starting Position : 6846
  • Gene Ending Position : 8739
  • Gene Strand (Orientation) : +
  • Protein Name : mRNA
  • Protein pI : 7.96
  • Protein Weight : 61174.65
  • Protein Length : 575
  • DNA Sequence : Show Sequence
    >NC_003461.1:6846-8739 Human parainfluenza virus 1, complete genome
    TAGGGTTAAAGACAATCCAGTCAACCTATAAGGCAACAGCATCCGATTATACAAACGATGGCTGAAAAAG
    GGAAAACAAATAGTTCATATTGGTCTACAACCCGAAATGACAATTCCACGGTAAACACACACATTAATAC
    ACCAGCAGGAAGGACACACATCTGGCTACTGATTGCAACAACAATGCATACAGTATTGTCCTTCATTATC
    ATGATCCTATGCATTGACCTAATTATAAAACAAGACACTTGTATGAAGACAAACATCATGACAGTATCCT
    CCATGAACGAAAGTGCCAAAATAATCAAAGAGACAATCACAGAATTAATCAGACAAGAAGTAATATCAAG
    GACCATAAACATACAAAGTTCAGTACAAAGCGGGATCCCAATATTGTTAAACAAGCAAAGCAGAGATCTC
    ACACAATTAATAGAGAAGTCATGCAACAGACAGGAATTGGCTCAGATATGCGAAAACACCATTGCTATTC
    ACCATGCAGACGGCATATCTCCTCTGGACCCACACGATTTCTGGAGATGTCCCGTAGGGGAACCCCTACT
    GAGCAACAACCCCAATATCTCATTATTACCTGGACCAAGTCTACTTTCTGGATCCACCACAATTTCAGGA
    TGTGTTAGACTACCTTCATTATCAATTGGTGATGCAATATATGCGTATTCATCAAACTTAATCACTCAAG
    GATGTGCAGATATAGGGAAGTCATATCAGGTTTTACAATTAGGTTACATATCCTTAAATTCAGATATGTA
    TCCTGATTTAAACCCGGTAATTTCTCATACCTATGACATCAACGACAACAGGAAATCATGTTCTGTAATA
    GCTGCAGGAACAAGGGGTTATCAGTTATGCTCCTTGCCCACTGTGAATGAGACTACAGACTACTCGAGTG
    AAGGTATAGAAGATTTAGTATTTGACATATTAGATCTCAAGGGAAAGACCAAATCTCATCGATACAAAAA
    TGAAGATATAACTTTTGACCATCCTTTTTCTGCAATGTATCCGAGTGTAGGAAGTGGGATAAAAATTGAA
    AATACACTCATTTTCCTAGGGTACGGTGGCTTAACAACTCCGCTCCAAGGCGACACTAAGTGTGTGATAA
    ACAGATGTACCAATGTTAATCAGAGTGTTTGCAATGATGCTCTTAAGATAACTTGGCTAAAGAAAAGACA
    AGTTGTCAATGTCTTAATTCGTATCAATAATTATTTATCTGATAGGCCAAAGATTGTTGTCGAGACAATT
    CCAATAACTCAAAATTACTTAGGTGCCGAAGGTAGGCTACTTAAACTAGGTAAAAAGATCTACATATATA
    CTAGATCTTCAGGTTGGCACTCCAACCTGCAAATAGGATCATTAGATATCAACAACCCCATGACCATTAA
    ATGGGCGCCTCATGAAGTCCTGTCTCGACCAGGAAACCAAGACTGCAACTGGTACAACAGATGTCCGAGA
    GAATGCATATCAGGTGTATATACTGATGCATATCCACTATCTCCTGATGCAGTCAATGTTGCTACAACCA
    CACTGTACGCAAACACATCACGTGTTAATCCCACCATAATGTACTCAAATACCTCAGAAATTATCAACAT
    GCTAAGACTCAAGAATGTACAACTAGAGGCAGCATACACTACTACATCATGTATCACTCATTTCGGGAAG
    GGCTACTGCTTCCACATTGTTGAAATCAACCAAGCCAGCCTTAATACCTTACAACCTATGTTGTTCAAGA
    CAAGTATCCCTAAAATATGTAAAATCACATCTTGAGCAGATCAAGACCCAACACTATATCAATTATGTGA
    AAACCAGATATGATGTATAAAAATTTAAAAACAAAGCATGAATAGACATTTATATGACAAATAGAATAAG
    AAAA
  • Protein Sequence : Show Sequence
    >NP_604441.1 HN glycoprotein [Human respirovirus 1]
    MAEKGKTNSSYWSTTRNDNSTVNTHINTPAGRTHIWLLIATTMHTVLSFIIMILCIDLIIKQDTCMKTNI
    MTVSSMNESAKIIKETITELIRQEVISRTINIQSSVQSGIPILLNKQSRDLTQLIEKSCNRQELAQICEN
    TIAIHHADGISPLDPHDFWRCPVGEPLLSNNPNISLLPGPSLLSGSTTISGCVRLPSLSIGDAIYAYSSN
    LITQGCADIGKSYQVLQLGYISLNSDMYPDLNPVISHTYDINDNRKSCSVIAAGTRGYQLCSLPTVNETT
    DYSSEGIEDLVFDILDLKGKTKSHRYKNEDITFDHPFSAMYPSVGSGIKIENTLIFLGYGGLTTPLQGDT
    KCVINRCTNVNQSVCNDALKITWLKKRQVVNVLIRINNYLSDRPKIVVETIPITQNYLGAEGRLLKLGKK
    IYIYTRSSGWHSNLQIGSLDINNPMTIKWAPHEVLSRPGNQDCNWYNRCPRECISGVYTDAYPLSPDAVN
    VATTTLYANTSRVNPTIMYSNTSEIINMLRLKNVQLEAAYTTTSCITHFGKGYCFHIVEINQASLNTLQP
    MLFKTSIPKICKITS
  • Molecule Role : Protective antigen
  • Related Vaccine(s): MEDI-534
4. L protein
  • Gene Name : L protein
  • NCBI Protein GI : AYC76673
  • Other Database IDs : CDD:395756
    CDD:275046
  • Taxonomy ID : 11250
  • Gene Strand (Orientation) : ?
  • Protein Name : L
  • Protein pI : 8.89
  • Protein Weight : 240331.02
  • Protein Length : 2166
  • Protein Note : Mononegavirales RNA dependent RNA polymerase; pfam00946
  • Protein Annotation : (Tiong-Yip et al., 2014)L protein is a viral RNA-dependent RNA polymerase that contains multiple enzyme activities required for RSV replication.
  • Protein Sequence : Show Sequence
    >AYC76673.1 L [Human orthopneumovirus]
    MDPIINGSSANVYLTDSYLKGVISFSECNALGSYLFNGPYLKNDYTNLISRQSPLLEHMNLKKLTITQSL
    ISRYHKGELKLEEPTYFQSLLMTYKSMSSSEQIATTNLLKKIIRRAIEISDVKVYAILNKLGLKEKDRVK
    PNNNSGDENSVLTTIIKDDILSAVENNQSYTNSDKNYSVNQNINIKTTLLKKLMCSMQHPPSWLIHWFNL
    YTKLNNILTQYRSNEVKSHGFILIDNQTLSGFQFILNQYGCIVYHKGLKRITTTTYNQFLTWKDISLSRL
    NVCLITWISNCLNTLNKSLGLRCGFNNVVLSQLFLYGDCILKLFHNEGFYIIKEVEGFIMSLILNITEED
    QFRKRFYNSMLNNITDAAIKAQKDLLSRVCHTLLDKTVSDNIINGKWIILLSKFLKLIKLAGDNNLNNLS
    ELYFLFRIFGHPMVDERQAMDAVRVNCNETKFYLLSSLSTLRGAFIYRIIKGFVNTYNRWPTLRNAIVLP
    LRWLNYYKLNTYPSLLEITGNDLIILSGLRFYREFHLPKKVDLEMIINDKAISPPKDLIWTSFPRNYMPS
    HIQNYIEHEKLKFSESDRSRRVLEYYLRDNKFNECDLYNCVVNQSYLNNSNHVVSLTGKERELSVGRMFA
    MQPGMFRQIQILAEKMIAENILQFFPESLTRYGDLELQKILELKAGISNKSNRYNDNYNNYISKCSIITD
    LSKFNQAFRYETSCICSDVLDELHGVQSLFSWLHLTIPLVTIICTYRHAPPFIKDHVVNLNEVDEQSGLY
    RYHMGGIEGWCQKLWTIEAISLLDLISLKGKFSITALINGDNQSIDISKPVRLIEGQTHAQADYLLALNS
    LKLLYKEYAGIGHKLKGTETYISRDMQFMSKTIQHNGVYYPASIKKVLRVGPWINTILDDFKVSLESIGS
    LTQELEYRGESLLCSLIFRNIWLYNQIALQLRNHALCNNKLYLDILKVLKHLKTFFNLDSIDTALSLYMN
    LPMLFGGGDPNLLYRSFYRRTPDFLTEAIVHSVFVLSYYTGHDLQDKLQDLPDDRLNKFLTCVITFDKNP
    NAEFVTLMRDPQALGSERQAKITSEINRLAVTEVLSIAPNKIFSKSAQHYTTTEIDLNDIMQNIEPTYPH
    GLRVVYESLPFYKAEKIVNLISGTKSITNILEKTSAIDTTDINRATDMMRKNITLLIRILPLDCNKDKRE
    LLSLENLSITELSKYVRERSWSLSNIVGVTSPSIMFTMDIKYTTSTIASGIIIEKYNVNGLTRGERGPTK
    PWVGSSTQEKKTMPVYNRQVLTKKQRDQIDLLAKLDWVYASIDNKDEFMEELSTGTLGLSYEKAKKLFPQ
    YLSVNYLHRLTVSSRPCEFPASIPAYRTTNYHFDTSPINHVLTEKYGDEDIDIVFQNCISFGLSLMSVVE
    QFTNICPNRIILIPKLNEIHLMKPPIFTGDVDIIKLKQVIQKQHMFLPDKISLTQYVELFLSNKALKSGS
    HINSNLILVHKMSDYFHNAYILSTNLAGHWILIIQLMKDSKGIFEKDWGEGYITDHMFINLNVFFNAYKT
    YLLCFHRGYGKAKLECDMNTSDLLCVLELIDSSYWKSMSKVFLEQKVIKYIVNQDTSLHRIKGCHSFKLW
    FLKRLNNAKFTVCPWVVNIDYHPTHMKAILSYIDLVRMGLINVDKLTIKNKNKFNDEFYTSNLFYISYNF
    SDNTHLLTKQIRIANSELEDNYNKLYHPTPETLENISLIPVKSNNRNKPKFCISGNTESMMTSTFSNKMH
    IKSSTVTTRFNYSRQDLYNLFPIVVIDRIIDHSGNTEKSNQLYTTTSHQTSLVRNSASLYCMLPWHHVNR
    FNFVFSSTGCKISIEYILKDLKIKDPNCIAFIGEGAGNLLLRTVVELHPDIRYIYRSLKDCNDHSLPIEF
    LRLYNGHINIDYGENLTIPATDATNNIHWSYLHIKFAEPISIFVCDAELPVTANWSKIIIEWSKHVRKCK
    YCSSVNRCILIAKYHAQDDIDFKLDNITILKTYVCLGSKLKGSEVYLVLTIGPANILPVFDVVQNAKLIL
    SRTKNFIMPKKIDKESIDANIKSLIPFLCYPITKNGIKISLSKLKSVVNGDILSYSIAGRNEVFSNKLIN
    HKHMNILKWLDHVLNFRSAELNYNHLYMIESTYPYLSELLNSLTTNELKKLIKITGSVLYNLPNEQ
  • Molecule Role : Protective antigen
5. M protein
  • Gene Name : M protein
  • NCBI Protein GI : AHB33452
  • Taxonomy ID : 11250
  • Gene Strand (Orientation) : ?
  • Protein Name : M
  • Protein pI : 8.57
  • Protein Weight : 27189.22
  • Protein Length : 256
  • Protein Note : subgroup: B; genotype: BA
  • Protein Annotation : (Shahriari et al., 2018)The M protein is a non-glycosylated phosphorylated protein located external to the nucleocapsid layer, where it acts as a bridge between the lipid bilayer envelope and the nucleocapsid.
  • Protein Sequence : Show Sequence
    >AHB33452.1 M [Human orthopneumovirus]
    METYVNKLHEGSTYTAAVQYNVLEKDDDPASLTIWVPMFQSSVPADLLIKELASINILVKQISTPKGPSL
    RVTINSRSAVLAQMPSNFTISANVSLDERSKLAYDVTTPCEIKACSLTCLKVKSMLTTVKDLTMKTFNPT
    HEIIALCEFENIMTSKRVIIPTYLRSISVKNKDLNSLENIATTEFKNAITNAKIIPYAGLVLVITVTDNK
    GAFKYIKPQSQFIVDLGAYLEKESIYYVTTNWKHTATRFSIKPLED
  • Molecule Role : Virmugen
  • Related Vaccine(s): Mnull RSV
6. M2-1
  • Gene Name : M2-1
  • NCBI Protein GI : AIO08080
  • Other Database IDs : CDD:214632
    CDD:399442
  • Taxonomy ID : 1545857
  • Gene Strand (Orientation) : ?
  • Protein Name : M2-1
  • Protein pI : 9.21
  • Protein Weight : 22207.54
  • Protein Length : 258
  • Protein Note : zinc finger; smart00356
  • Protein Sequence : Show Sequence
    >AIO08080.1 M2-1 [Human respiratory syncytial virus MinFLC]
    MSRRNPCKFEIRGHCLNGKRCHFSHNYFEWPPHALLVRQNFMLNRILKSMDKSIDTLSEISGAAELDRTE
    EYALGVVGVLESYIGSINNITKQSACVAMSKLLTELNSDDIKKLRDNEELNSPKIRVYNTVISYIESNRK
    NNKQTIHLLKRLPADVLKKTIKNTLDIHKSITINNPKESTVSDTNDHAKNNDTT
  • Molecule Role : Protective antigen
  • Related Vaccine(s): MVA - RSV
7. M2-2
  • Gene Name : M2-2
  • Sequence Strain (Species/Organism) : Human respiratory syncytial virus A2
  • NCBI Protein GI : 81925031
  • Other Database IDs : CDD:116003
  • Taxonomy ID : 11259
  • Gene Strand (Orientation) : ?
  • Protein Name : Matrix M2-2
  • Protein Length : 90
  • Protein Note : Matrix M2-2. /FTId=PRO_0000356857.
  • Protein Sequence : Show Sequence
    >gi|81925031|sp|P88812.1|M22_HRSVA RecName: Full=Matrix M2-2
    MTMPKIMILPDKYPCSITSILITSRCRVTMYNQKNTLYFNQNNPNNHMYSPNQTFNEIHWTSQELIDTIQ
    NFLQHLGIIEDIYTIYILVS
  • Molecule Role : Virmugen
  • Molecule Role Annotation : An M2-2 mutant of human respiratory syncytial virus A2 is attenuated in African green monkeys. When challenged with wild type RSV, two doses provided complete protection against challenge in the lower respiratory tract and a significant reduction of the challenge virus in the upper respiratory tract (Jin et al., 2003).
  • Related Vaccine(s): D46/NS2/N/ΔM2-2-HindIII , Human Respiratory Syncytial Virus M2-2 mutant vaccine , LID/ΔM2-2/1030s
8. N protein
  • Gene Name : N protein
  • Sequence Strain (Species/Organism) : 18537/Human orthopneumovirus
  • NCBI Protein GI : BAA00637
  • Other Database IDs : CDD:397378
  • Taxonomy ID : 11250
  • Gene Strand (Orientation) : ?
  • Protein Name : N protein
  • Protein pI : 7.12
  • Protein Weight : 41228.94
  • Protein Length : 391
  • Protein Note : clones C9, G15, B53, E41, R4, F5, D35, C85, AA75, and 7N30;
    subgroup B
  • Protein Annotation : Protective antigen
  • Protein Sequence : Show Sequence
    >BAA00637.1 N protein [Human orthopneumovirus]
    MALSKVKLNDTLNKDQLLSSSKYTIQRSTGDNIDTPNYDVQKHLNKLCGMLLITEDANHKFTGLIGMLYA
    MSRLGREDTIKILKDAGYHVKANGVDITTYRQDINGKEMKFEVLTLSSLTSEIQVNIEIESRKSYKKLLK
    EMGEVAPEYRHDSPDCGMIILCIAALVITKLAAGDRSGLTAVIRRANNVLKNEIKRYKGLIPKDIANSFY
    EVFEKHPHLIDVFVHFGIAQSSTRGGSRVEGIFAGLFMNAYGSGQVMLRWGVLAKSVKNIMLGHASVQAE
    MEQVVEVYEYAQKLGGEAGFYHILNNPKASLLSLTQFPNFSSVVLGNAAGLGIMGEYRGTPRNQDLYDAA
    KAYAEQLKENGVINYSVLDLTAEELEAIKHQLNPKEDDVEL
  • Molecule Role : Defense factor
  • Molecule Role Annotation : (Oliveira et al., 2013)N protein interacts with viral RNA, generating a helicoidal nucleocapsid, responsible for genome and antigenome resistance to RNAse. RSV nucleoprotein (N) is essential for virus assembly and replication as part of the viral ribonucleoprotein (RNP) complex.
  • Related Vaccine(s): (rBCG-N-hRSV) Recombinant Mycobacterium bovis BCG vaccine , MVA - RSV
9. NS1 Protein
  • Gene Name : NS1 Protein
  • Sequence Strain (Species/Organism) : Human respiratory syncytial virus B
  • NCBI Protein GI : CBW47561
  • Protein Accession : CBW47561
  • Other Database IDs : CDD:367500
    InterPro: IPR005099
    UniProtKB/TrEMBL: E0WMQ1
  • Taxonomy ID : 208895
  • Gene Strand (Orientation) : ?
  • Protein Name : NS1 protein
  • Protein pI : 5.07
  • Protein Weight : 15471.47
  • Protein Length : 139
  • Protein Note : Pneumovirus NS1 protein; pfam03438
  • Protein Annotation : Protective Antigen
  • Protein Sequence : Show Sequence
    >CBW47561.1 NS1 protein [Human respiratory syncytial virus B]
    MGCNSLSMIKVRLQNLFDNDEVALLKITCYTDKLILLTNALAKATIHTIKLNGIVFIHVITSSEACPDNN
    IVVKSNFTTMPILQNGGYIWELIELTHCSQLNGLMDDNCEIKFSKRLSDSVMTDYMNQISDLLGLDLNP
  • Molecule Role : Protective antigen
  • Additional Molecule Role Annotation : (Chatterjee et al., 2017)The NS1 protein (139 amino acids) is encoded by a very abundant mRNA transcribed from the promoter proximal RSV gene. NS1 proteins are important immune antagonists, but there is still more research being done on the role of the proteins in viral pathogenesis.
10. NS2
  • Gene Name : NS2
  • NCBI Protein GI : AIO08073
  • Other Database IDs : CDD:427145
  • Taxonomy ID : 1545857
  • Gene Strand (Orientation) : ?
  • Protein Name : NS2
  • Protein pI : 8.78
  • Protein Weight : 15420.92
  • Protein Length : 186
  • Protein Note : Respiratory synctial virus non-structural protein NS2; pfam03113
  • Protein Annotation : (Pei et al., 2021)NS2 inhibits host interferon (IFN) responses stimulated by RSV infection by targeting early steps in the IFN-signaling pathway.
  • Protein Sequence : Show Sequence
    >AIO08073.1 NS2 [Human respiratory syncytial virus MinFLC]
    MDTTHNDNTPQRLMITDMRPLSLETIITSLTRDIITHKFIYLINHECIVRKLDERQATFTFLVNYEMKLL
    HKVGSTKYKKYTEYNTKYGTFPMPIFINHDGFLECIGIKPTKHTPIIYKYDLNP
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (Pei et al., 2021)NS2 binding prevents RLR ubiquitination, a process critical for prolonged activation of downstream signaling. N terminus of NS2 is essential for binding to the RIG-I caspase activation and recruitment domains.
11. P protein
  • Gene Name : P protein
  • NCBI Protein GI : BAA00638
  • Other Database IDs : CDD:280615
  • Taxonomy ID : 11250
  • Gene Strand (Orientation) : ?
  • Protein Name : P protein
  • Protein pI : 4.29
  • Protein Weight : 26758.47
  • Protein Length : 241
  • Protein Note : clones C9, G15, B53, E41, R4, F5, D35, C85, AA75, and 7N30;
    subgroup B
  • Protein Annotation : (Simabuco et al., 2011)One of the P protein functions is to allow specificity of the N protein to the vRNA encapsulation and another is to confer stability of the L protein in the ribonucleop-complex. P proteins are also able to oligomerize in tetramers.
  • Protein Sequence : Show Sequence
    >BAA00638.1 P protein [Human orthopneumovirus]
    MEKFAPEFHGEDANNKATKFLESIKGKFASSKDPKKKDSIISVNSIDIEVTKESPITSGTNIINPISEAD
    STPEAKANYPRKPLDSFKEDLTPSDNPFSKLYKETIETFDNNEEESSYSYEEINDQTNDNITARLDRIDE
    KLSEILGMLHTLVVASAGPTSARDGIRDAMVGLREEMIEKIRAEALMTNDRLEAMARLRNEESEKMAKDT
    SDEVSLNPTSKKLSNLLEDNDSDNDLSLDDF
  • Molecule Role : Other
12. RSV Prefusion F protein based
  • Gene Name : RSV Prefusion F protein based
  • NCBI Protein GI : UED36857
  • Other Database IDs : CDD:395418
  • Taxonomy ID : 32630
  • Gene Strand (Orientation) : ?
  • Protein Name : prefusion RSV F protein
  • Protein pI : 9.11
  • Protein Weight : 59319.97
  • Protein Length : 574
  • Protein Note : derived from human respiratory syncytial virus A2
  • Protein Sequence : Show Sequence
    >UED36857.1 prefusion RSV F protein [synthetic construct]
    MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKKNKCN
    GTDAKVKLIKQELDKYKNAVTELQLLMQSTQATNNKAKKELPRFMNYTLNNAKKTNVTLSKKKKKKFLGF
    LLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQ
    SCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQI
    VRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVS
    FFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKT
    KCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDA
    SISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARSTPVTLS
    KDQLSGINNIAFSN
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The F protein exists in a metastable prefusion conformation (RSV Prefusion F protein) that is anchored in the viral membrane by a transmembrane domain. In this conformation the hydrophobic fusion peptide is buried within the central cavity of the protein(Gilman et al., 2019).
  • Related Vaccine(s): Ad26/protein preF RSV Vaccine Coadministered With an Influenza Vaccine
13. RSV strain A2
  • Gene Name : RSV strain A2
  • Gene Strand (Orientation) : ?
  • Molecule Role : Virmugen
  • Related Vaccine(s): RSV/ΔNS2/Δ1313/I1314
14. SH
  • Gene Name : SH
  • NCBI Protein GI : ASU47779
  • Locus Tag : ASU47779
  • Protein Accession : ASU47779
  • Other Database IDs : CDD:281565
  • Taxonomy ID : 208895
  • Gene Strand (Orientation) : ?
  • Protein Name : small hydrophobic protein
  • Protein pI : 8.51
  • Protein Weight : 7860.84
  • Protein Length : 64
  • Protein Note : J163;
    genotype: BA9
  • Protein Annotation : (Gan et al., 2012) SH protein has a single α-helical transmembrane domain and forms homopentamers in several detergents
  • Protein Sequence : Show Sequence
    >ASU47779.1 small hydrophobic protein [Human respiratory syncytial virus B]
    MGNTSITIEFTSKFWPYFTLIHMILTLISLLIIITIMIAILNKLSEHKTFCNKTLEQGQMYQINT
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (Gan et al., 2012) Without the SH protein, it leads to viral attenuation and it prevents apoptosis in infected cells.
III. Vaccine Information
1. (rBCG-N-hRSV) Recombinant Mycobacterium bovis BCG vaccine
a. Product Name:
rBCG-N-hRSV
b. Manufacturer:
IDT Biologika
c. Type:
Recombinant vector vaccine
d. Status:
Clinical trial
e. Location Licensed:
Pontifcia Universidad Catholics de Chile
f. Host Species for Licensed Use:
None
g. Antigen
(Abarca et al., 2020) N protein
h. Vector:
(Abarca et al., 2020) Bacillus Calmette-Guerin-Gudrun (BCG) is used as a vector.
i. Preservative:
(Abarca et al., 2020) Antigen T cells
j. Preparation
0.05 mL of a reconstituted vial (2-8*10^6 CFU of the bacteria per 0.1 mL) of this vaccine is administered. This results in 1-4*10^5 CFU to a newborn.
k. Immunization Route
Intradermal injection (i.d.)
l. Description
(Abarca et al., 2020) rBCG-N-hRSV is a live attenuated recombinant Mycobacterium bovis BCG based on the Danish strain 1331 that expresses the nucleoprotein (N) of RSV (rBCG-N-hRSV)(BCG) that expresses the nuclei protein (N) of RSV.
m. Human Response
  • Host Strain: Danish strain
  • Vaccination Protocol: In each cohort, participants were vaccinated with 0.1 mL of the vaccine, as follows: 6 volunteers in Cohort A were vaccinated with the lowest dose (5 × 10^3 CFU); 6 volunteers in Cohort B received the middle dose (5 × 10^4 CFU); 6 volunteers in Cohort C received the highest dose (1 × 10^5 CFU) of the study vaccine. Each cohort included two volunteers vaccinated with 0.1 mL of the standard BCG vaccine (BCG-WT; a full dose of 1-33 × 10^5 CFU).
  • Vaccination Groups:
    No. Group Name Number of Animals Dose Route Gender Age Control Group? Comment Vaccination Detail
    1 BCG control vaccine 1-33*10^5 CFU in volume 0.1 ml Intradermal injection (i.d.) male 18-50 year yes Each cohort included 2 volunteers with the standard BCG vaccine as the control group
    2 Cohort A 5*10^3 CFU in volume 0.1 ml Intradermal injection (i.d.) male 18-50 year no
    3 Cohort B 5*10^4 CFU in volume 0.1 ml Intradermal injection (i.d.) male 18-50 year no
    4 Cohort C 1*10^5 CFU in volume 0.1 ml Intradermal injection (i.d.) male 18-50 year no
  • Immune Response: (Abarca et al., 2020) Both immunogenicity and reactogenicity responses were lower in BCG-WT immunized volunteers as compared to volunteers immunized with the study vaccine. N-RSV immune responses increased with higher doses of the vaccine
  • Side Effects: (Abarca et al., 2020) General (systemic) solicited AEs included fever, tachycardia, hypo/hypertension, headache, fatigue, myalgia, nausea/vomiting, and diarrhea.
  • Challenge Protocol: The findings with rBCG-N-hRSV vaccine are consistent with previous studies that showed that it induces a Th-1 RSV-specific immune response in mice, which was protective against RSV challenge
  • Efficacy: (Abarca et al., 2020) rBCG-N-hRSV vaccine candidate was safe, well tolerated, and immunogenicity in healthy male adult volunteers. Both immunogenicity and reactogenicity responses were lower in control group as compared to volunteers immunized with the study vaccine. Individuals did not show enhancement of RSV disease.
2. Ad26/protein preF RSV Vaccine Coadministered With an Influenza Vaccine
a. Tradename:
Fluarix
b. Manufacturer:
Janssen (Leiden, the Netherlands)
c. Type:
Other
d. Status:
Licensed
e. Host Species for Licensed Use:
Human
f. Antigen
4 virus strains (15 μg of hemagglutinin per strain per 0.5-mL dose): A/Singapore/GP1908/2015 (H1N1) IVR-180, A/Hong Kong/4801/2014 (H3N2) NYMC X-263B, B/Phuket/3073/2013, and B/Brisbane/60/2008. The placebo was sterile 0.9% saline.
g. Vector:
(Sadoff et al., 2021)An adenovirus serotype 26 (Ad26) vector
h. Preparation
(Sadoff et al., 2021) Each 0.5-mL dose contained 1 × 1011 viral particles (vp) of Ad26.RSV.preF. Fluarix Quadrivalent (GlaxoSmithKline), formulated for the 2017–2018 Northern Hemisphere season, contained the following 4 virus strains (15 μg of hemagglutinin per strain per 0.5-mL dose): A/Singapore/GP1908/2015 (H1N1) IVR-180, A/Hong Kong/4801/2014 (H3N2) NYMC X-263B, B/Phuket/3073/2013, and B/Brisbane/60/2008. The placebo was sterile 0.9% saline.
i. Immunization Route
Intramuscular injection (i.m.)
j. Description
(Sadoff et al., 2021) The vaccine Ad26.RSV.preF is the next-generation vaccine expressing the stabilized FA2. The vaccine is a replication-incompetent Ad26 vector containing a DNA transgene, encoding a F protein derived from the RSV A2 strain that is stabilized in its pre-F conformation
k. Human Response
  • Vaccination Protocol: In this phase 2a, double-blind, placebo-controlled study, 180 adults aged ≥60 years received Ad26.RSV.preF plus Fluarix on day 1 and placebo on day 29, or placebo plus Fluarix on day 1 and Ad26.RSV.preF on day 29 (control).
  • Challenge Protocol: (Sadoff et al., 2021) Adenoviral vectors adenovirus serotypes 26 and 35 (Ad26 and Ad35), expressing the nonstabilized form of the F protein of the RSV strain A2 induced strong RSV specific humoral and cellular immune responses in mice and were protective in the cotton rat challenge model. Ad26 vectors encoding the RSV F glycoprotein, the most immunogenic antigen in a RSV vaccine [24, 26, 28], have demonstrated high and durable RSV neutralizing antibody titers, a T-helper 1–type cellular immune response and protective immunity in an animal challenge model
  • Efficacy: Reported systemic reactogenicity and those graded 3 were generally more frequent after dosing with Ad26.RSV.preF than with Fluarix alone. Systemic reactogenicity was also higher after vaccination with Ad26.RSV.preF alone and in combination with Fluarix in this study than after vaccination with Ad26.RSV.preF alone, as previously reported in study VAC18193RSV1003 for a similar age group. Ad26.RSVpreF was generally well tolerated and had an acceptable safety profile(Sadoff et al., 2021)
3. Ad5-RSV-F
a. Type:
Recombinant vector vaccine
b. Status:
Research
c. Host Species for Licensed Use:
None
d. Preparation
Adenovirus serotype 5-based RSV vaccine encoding the fusion (F) protein (Ad5.RSV-F)(Kim et al., 2014)
e. Immunization Route
Intramuscular injection (i.m.)
f. Rat Response
  • Vaccination Protocol: Animals were immunized intranasally (i.n.) and/or intramuscularly (i.m.) with Ad5.RSV-F (Kim et al., 2014)
  • Challenge Protocol: (Kim et al., 2014)Post vaccination, animals were subsequently challenged with RSV/A/Tracy (i.n.)
  • Efficacy: (Kim et al., 2014)The vaccine provided protective immunity against RSV challenge without enhanced lung disease in the rats
4. D46/NS2/N/ΔM2-2-HindIII
a. Manufacturer:
Charles river Laboratories
b. Type:
Live, attenuated vaccine
c. Status:
Licensed
d. Host Species for Licensed Use:
Human
e. Gene Engineering of M2-2
  • Type: Deletion
  • Description: (McFarland et al., 2020)The vaccine uses backbone of LId/M2-2 vaccine but has a 234 nucleotide M2-2 deletion with the same structure as in MEDI/m2-2
  • Detailed Gene Information: Click here.
f. Immunization Route
intranasal immunization
g. Description
(McFarland et al., 2020)The vaccine, D46/NS2/N/ΔM2-2-HindIII, is a cDNA-derived version of RSV subgroup A, strain A2. In addition, D46/NS2/N/ΔM2-2-HindIII has the MEDI/ΔM2-2 assignments at the only 2 amino acid positions that differ between MEDI/ΔM2-2 and LID/ΔM2-2. D46/NS2/N/ΔM2-2-HindIII contains the complete 112-nucleotide 3’ noncoding region of the SH gene that is present in biological RSV A2 but was deleted in LID/ΔM2-2. D46/NS2/N/ΔM2-2-HindIII was recovered from cDNA in qualified Vero cells.
h. Human Response
  • Vaccination Protocol: he study included children ≥6 and <25 months of age who were healthy, had no current or past lung disease, and were RSV seronegative at screening (McFarland et al., 2020)
  • Side Effects: During the 28 days after inoculation, mild upper respiratory tract and/or febrile events occurred in both vaccine and placebo recipients, with 76%. All respiratory symptoms in both groups were grade 1. Grade 2 fever occurred in 1 vaccinee and 1 placebo recipient. Of the 16 vaccinees with respiratory or febrile illness, illness was concurrent with vaccine alone detected in NW specimens in 12, vaccine plus rhinovirus in 2, vaccine plus rhinovirus and adenovirus in 1, and parainfluenza type 4 and no vaccine virus in 1. (McFarland et al., 2020)
  • Efficacy: (McFarland et al., 2020) When administered to RSV-naive 6–24 month-old infants and children, the RSV D46/NS2/N/ΔM2-2-HindIII candidate vaccine was well tolerated, was highly infectious (100% of participants had evidence of vaccine shedding and/or a serum RSV antibody response), and resulted in excellent induction of serum RSV-specific antibodies, including neutralizing antibodies.
  • Description: (McFarland et al., 2020)The D46/NS2/N/ΔM2-2-HindIII vaccine had excellent infectivity and generated robust neutralizing antibody and anti-RSV F protein IgG responses.
5. HDAd-sFsyn
a. Vaccine Ontology ID:
VO_0004802
b. Type:
Recombinant vector vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Baboon
e. Preparation
(Fu et al., 2014)
f. Immunization Route
Intramuscular injection (i.m.)
6. HRSV DNA vaccine DRF-412
a. Vaccine Ontology ID:
VO_0004579
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of F protein
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
f. Vector:
phCMV1 (Wu et al., 2009)
g. Immunization Route
Intramuscular injection (i.m.)
h. Mouse Response
  • Vaccine Immune Response Type: VO_0003057
  • Immune Response: The DRF-412 vaccine vector was as effective as live RSV in inducing neutralization antibody, systemic Ab (IgG, IgG1, IgG2a, and IgG2b) responses, and mucosal antibody responses (Ig A). Mice inoculated with vector DRF-412 induced a higher mixed Th1/Th2 cytokine immune response than DRF-412-P (Wu et al., 2009).
  • Efficacy: Mice immunized with DRF-412 and DRF-412-P have a higher average Ct value compared with PBS and phCMV I group (P < 0.001), which means that they have less viral mRNA in the lung indicating better protection, but there was no statistically significant difference between DRF-412 and DRF-412-P. This vaccine induced partial protection against RSV in mice (Wu et al., 2009).
7. HRSV DNA vaccine pND-G
a. Vaccine Ontology ID:
VO_0004580
b. Type:
DNA vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of G
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
f. Vector:
pND (Miller et al., 2002)
g. Immunization Route
Intradermal injection (i.d.)
h. Mouse Response
  • Vaccine Immune Response Type: VO_0003057
  • Efficacy: Immunization with the pND-G vaccine significantly inhibited the RSV induced increase in airway responsiveness to methacholine (Mch) (n=3 separate experiments; 12 mice per group) (P<0.05 versus RSV). The concentration of Mch required to induce a 200% increase in airway responsiveness (PC200) was significantly greater in RSV infected mice who had received the pND-G vaccine compared to RSV infected mice who had not received the vaccine (21.5 mg/ml Mch versus 7.2 mg/ml Mch) (P<0.05) (Miller et al., 2002).
8. Human Respiratory Syncytial Virus M2-2 mutant vaccine
a. Vaccine Ontology ID:
VO_0002978
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
African green monkey
e. Gene Engineering of M2-2
  • Type: Gene mutation
  • Description: This M2-2 is from Human Respiratory Syncytial Virus (Jin et al., 2003).
  • Detailed Gene Information: Click here.
f. Immunization Route
intranasal immunization
g. Monkey Response
  • Persistence: An M2-2 mutant is attenuated in African green monkeys (Jin et al., 2003).
  • Efficacy: An M2-2 mutant induces significant protection in African green monkeys from challenge with wild type HRSV (Jin et al., 2003).
9. LID/ΔM2-2/1030s
a. Manufacturer:
Charles River Laboratories Malvern, PA
b. Type:
Live, attenuated vaccine
c. Status:
Clinical trial
d. Host Species for Licensed Use:
None
e. Gene Engineering of M2-2
  • Type: Recombinant protein preparation
  • Description: 241 deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 (McFarland et al., 2020).
  • Detailed Gene Information: Click here.
f. Immunization Route
Intramuscular injection (i.m.)
g. Description
The vaccine, LID/ΔM2-2/1030s, is a cDNA-derived version of RSV subgroup A, strain A2 with 241 nts deleted from the M2-2 ORF and the 3 potential translation initiation codons of the M2-2 ORF silenced (McFarland et al., 2020).
h. Human Response
  • Vaccination Protocol: (McFarland et al., 2020)Eligible children were RSV seronegative at screening, defined as having a complement-enhanced serum RSV 60% plaque reduction neutralizing titer. Respiratory syncytial virus-seronegative children ages 6–24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored.
  • Challenge Protocol: (McFarland et al., 2020)The small sample size precludes firm estimates of rates of vaccine-associated events, infectivity, immunogenicity, and viral replication.
  • Efficacy: (McFarland et al., 2020)Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV.
  • Description: The vaccine, LID/ΔM2-2/1030s, is a cDNA-derived version of RSV subgroup A, strain A2. The results showed that the LID/∆M2-2/1030s is a very attractive candidate for further development as a live attenuated in trans Al pediatric RSV vaccine.
10. MEDI-534
a. Manufacturer:
MedImmune LLC
b. Type:
Recombinant vector vaccine
c. Status:
Clinical trial
d. Host Species for Licensed Use:
Human
e. Gene Engineering of HN
  • Type: Recombinant protein preparation
  • Description: Bovine parainfluenza virus type 3 genome was substituted with HN glycoproteins.(Yang et al., 2013)
  • Detailed Gene Information: Click here.
f. Gene Engineering of F protein
  • Type: Recombinant protein preparation
  • Description: Substituting the human PIV3 F and HN glycoproteins to express RSV F protein (Yang et al., 2013).
  • Detailed Gene Information: Click here.
g. Vector:
Consists of the bovine parainfluenza virus type 3 (PIV3).
h. Preparation
The bovine parainfluenza virus type 3 (PIV3) genome was substituted with human PIV3 F and HN glycoproteins engineered to express RSV F protein.(Yang et al., 2013)
i. Immunization Route
intranasal immunization
j. Description
MEDI 534 is a live attenuated type 3 vectored RSV vaccine intransally administered and engineered to express RSV F, neutralizing antibodies against both RSV A and B subtypes.(Yang et al., 2013)
11. Mnull RSV
a. Type:
Live, attenuated vaccine
b. Status:
Clinical trial
c. Host Species for Licensed Use:
None
d. Host Species as Laboratory Animal Model:
Baboons
e. Antigen
Fusion (F) protein
f. Gene Engineering of M protein
g. Preparation
RSV M protein was deleted (Ivanov et al., 2021).
h. Immunization Route
intranasal immunization
i. Description
Mnull RSV is derived from a human RSV A2 strain. The gene for the RSV M protein has been deleted. Mnull RSV is grown in HEp-2 respiratory epithelial cells transfected to express the viral M protein. The vaccine virus is fully infectious, and synthesizes all of its proteins (except M) after entering HEp-2 cells (Ivanov et al., 2021).
12. MVA - RSV
a. Manufacturer:
Bavarian Nordic
b. Type:
Recombinant vector vaccine
c. Status:
Licensed
d. Host Species for Licensed Use:
Human
e. Host Species as Laboratory Animal Model:
Used two mouse models to shed light on MVA RSV induced immune mechanisms of protection against RSV infection.
f. Antigen
(Endt et al., 2022) RSV fusion protein (F), glycoprotein (G), nucleoprotein (N), transcription elongation factor from RSV A, and glycoprotein from RSV strain B.
g. Vector:
(Endt et al., 2022)This vaccine is based on the attenuated virus Vector, modified Vaccinia Ankara Bavarian Nordic, encoding the RSV fusion protein (F), glycoprotein (G), nuclei protein (N), and transcription elongation factor derived from RSV subtype A, as well as another G of RSV subtype B.
h. Preparation
(Endt et al., 2022)MVA-RSV was generated by homologous recombination. Primary Chicken embryo fibroblast cells were infected with MVA -BN and transferred with recombination plasmids. During homologous recombination, sequences within the plasmid homologous to the insertion sites of the MVA - BN genome recombine with their corresponding sequences within the viral genome and target the trans genes into the respective integration site of MVA - BN. MVA-RSV was further propagated in CEF cells at serum-free conditions. After insertion of the antigens into the MVA-BN genome, genetically pure clones were isolated by repeated rounds of limiting dilution and plaque purification. were isolated by repeated rounds of limiting dilution and plaque purification. A final clone was amplified, and a stock was prepared.
i. Immunization Route
intranasal immunization
j. Storage
(Endt et al., 2022) Production was conducted in roller bottles seeded with primary CEF cells under serum-free conditions. Infected CEF lysates were sonicated, purified, and concentrated using a standardized two-step sucrose cushion centrifugation procedure. Vaccine infectious titer, sequence identity, and integrity were confirmed.
k. Description
(Endt et al., 2022)The MVA RSV contains five SV specific antigens that induced antibody and T cell responses which is currently being tested in the clinical trials for people older than 55 years of age. Depletion of CD4 or CD8 T cells, serum transfer, and the use of genetically engineered mice lacking the ability to generate either RSV-specific antibodies, the IgA isotope, or CD8 T cells revealed that complete protection from RSV infection is dependent on CD4 and CD8 T cells as well as antibodies, including IgA. MVA-RSV vaccination optimally protects against RSV infection by employing multiple arms of the adaptive immune system.
l. Mouse Response
  • Vaccination Protocol: (Endt et al., 2022)IgA deficient mice at the age of 12 to 24 weeks, CD8 deficient mice the insertion sites of the MVA - BN genome recombine with their corresponding sequences within the viral genome and target the trans genes into the respective integration site of MVA - BN. Mice were administered intranasally (IN) with 100 μl of the MVA-RSV vaccine at 1 × 108 TCID50 per dose at Days 0 and 21. IN challenge was performed with 100 μl of RSV-A2 at 1 × 106 pfu at Day 35 (9, 15). Control animals received TRIS-buffered saline, pH 7.7. For IN applications, mice were anesthetized with a mixture of Fentanyl, Midazolam, and Medetomidine and anesthesia was antagonized with a mixture of Naloxone, Flumazenil, and Atipamezole. After challenge, animals were monitored daily, and body weight was measured. Animals were sacrificed 4 days post challenge.
  • Efficacy: (Endt et al., 2022) MSV - RSV induced both broad T cell responses against all encoded RSV antigens and humoral responses against RSV A and RSV B. These results suggest that MVA - RSV may activate various adaptive immune responses against RSV that could contribute to different pathways of protection.
  • Description: (Endt et al., 2022)After vaccination with MVA-RSV, clearance of RSV from murine lungs was only complete in the presence of RSV-specific antibodies, including mucosal IgA, as well as CD4 and CD8 T cells. MVA-RSV induces immune parameters from all arms of the adaptive immune system, which together warrant sterilizing protection against RSV exposure.
13. rB-HPIV3-F1
a. Type:
Recombinant vector vaccine
b. Status:
Licensed
c. Host Species for Licensed Use:
Monkey
d. Preparation
Virus expressing the RSV F ORF (rB/HPIV3-F1)(Schmidt et al., 2001)
e. Immunization Route
Intramuscular injection (i.m.)
14. rB-HPIV3-G1
a. Type:
Recombinant vector vaccine
b. Status:
Licensed
c. Host Species for Licensed Use:
Hamster
d. Preparation
Recombinant PIV3 expressing the RSV G ORF (Schmidt et al., 2001)
e. Immunization Route
Intramuscular injection (i.m.)
15. rB/HPIV3- RSV-F
a. Type:
Recombinant vector vaccine
b. Status:
Research
c. Host Species for Licensed Use:
None
d. Gene Engineering of F protein
  • Type: Recombinant vector construction
  • Description: RSV F from the first (pre-N), second (N-P), third (P-M), and sixth (HN-L) genome positions is expressed in a recombinant vaccine vector rB/HPIV3 viruses (Liang et al., 2014).
  • Detailed Gene Information: Click here.
e. Preparation
rB/HPIV3 viruses expressing RSV F from the first (pre-N), second (N-P), third (P-M), and sixth (HN-L) genome positions (Liang et al., 2014),
f. Immunization Route
Intramuscular injection (i.m.)
g. Hamster Response
  • Vaccination Protocol: The hamsters were inoculated intranasally with 0.1 ml containing 10^6 TCID50 of rB/HPIV3-RSV F virus or with 10*6 PFU of wt RSV (A2 strain) (Liang et al., 2014) .
  • Challenge Protocol: Challenge was performed by intranasal infection with 106 PFU of RSV in 0.1 ml at 31 days after immunization(Liang et al., 2014)
  • Efficacy: Each rB/HPIV3 vector induced a high titer of neutralizing antibodies in hamsters against RSV and HPIV3. Protection against RSV challenge was greater for position 2 than for position 6. Evaluation of insert stability suggested that RSV F is under selective pressure to be silenced during vector replication in vivo, but this was not exacerbated by a high level of RSV F expression and generally involved a small percentage of recovered vector (Liang et al., 2014)
16. rBPIV3-RSV-G
a. Type:
Recombinant vector vaccine
b. Status:
Research
c. Host Species for Licensed Use:
None
d. Antigen
G and F protein (Falsey et al., 2022)
e. Gene Engineering of G
  • Type: Recombinant vector construction
  • Description:
  • Detailed Gene Information: Click here.
f. Preparation
bPIV3 as a virus vaccine vector with the introduction of the RSV attachment (G) and fusion (F) genes into the bPIV3 RNA genome(Haller et al., 2003)
g. Immunization Route
Intramuscular injection (i.m.)
h. Hamster Response
  • Vaccination Protocol: Hamsters were infected intranasally with 1×106  p.f.u. r-bPIV3, bPIV3/RSV(I), RSV or placebo (Opti-MEM) in a 0·1 ml volume(Haller et al., 2003)
  • Challenge Protocol: Animals were inoculated on day 21 intranasally with 1×106 p.f.u. of hPIV3 or RSV. (Haller et al., 2003)
  • Efficacy: The recombinant virus expressed the RSV G and F proteins sufficiently to evoke a protective immune response in hamsters upon challenge with RSV or human PIV3 and to elicit RSV neutralizing and PIV3 haemagglutinin inhibition serum antibodies. In effect, a bivalent vaccine was produced that could protect vaccinees from RSV as well as PIV3(Haller et al., 2003)
17. Respiratory syncytal virus bivalent prefusion F vaccine
a. Type:
Subunit vaccine
b. Status:
Clinical trial
c. Host Species for Licensed Use:
Human
d. Antigen
F protein
e. Gene Engineering of F protein
  • Type: Recombinant protein preparation
  • Description: A trimeric F glycoproteins from both major RSV subgroups (A and B) engineered for stability in the prefusion conformation is in clinical development in adults (Falsey et al., 2022).
  • Detailed Gene Information: Click here.
f. Adjuvant:
g. Immunization Route
Intramuscular injection (i.m.)
h. Description
A bivalent prefusion F vaccine (RSVpreF) containing trimeric F glycoproteins from both major RSV subgroups (A and B) engineered for stability in the prefusion conformation is in clinical development in adult (Falsey et al., 2022).
i. Human Response
  • Vaccination Protocol: Patient was given a single 60-µg, 120-µg or 240-µg dose on day 0.
  • Immune Response: Among older adults 65–85 years in the expanded cohort, RSV A 50% neutralizing GMTs in RSVpreF recipients increased from 1793–2734 before vaccination to 14 905–27 600 at 1 month postvaccination (Figure 3). RSV B neutralizing titers increased from 1635–2685 before vaccination to 15 169–30 071 at 1 month postvaccination. Postimmunization neutralizing titers were similarly high across RSVpreF dose levels and formulations; corresponding GMFRs were 7.2–13.2 for RSV A and 6.9–14.9 for RSV B across RSVpreF groups, and 1.1 for RSV A and 0.9 for RSV B for placebo recipients (findings were similar for older adults in the sentinel cohort.
  • Side Effects: 124/490 of participants in the RSVpreF cohorts had local reactions within 14 days post–vaccination. The majority (82.2% [102/124]) of participants who reported local reactions rated them mild in severity; pain at the injection site was the most common (22.2% [109/490]) (Falsey et al., 2022).
18. rPIV3-RSV-hMPV
a. Type:
Recombinant vector vaccine
b. Status:
Research
c. Host Species for Licensed Use:
Hamster
d. Gene Engineering of F protein
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
e. Immunization Route
Intramuscular injection (i.m.)
f. Hamster Response
  • Vaccination Protocol: The hamsters were vaccinated intranasally with 106 PFU of b/h PIV3, b/h PIV3/RSV, RSV A2, b/h PIV3/hMPV, hMPV/NL/1/00, or placebo medium in a 100-μl volume, (Tang et al., 2003)
  • Challenge Protocol: Animals were challenged intranasally with 106 PFU of RSV or hPIV3 per animal on day 28 postvaccination. (Tang et al., 2003)
  • Efficacy: Animals immunized with b/h PIV3/RSV were protected completely from hPIV3 and RSV infection. (Tang et al., 2003)
19. RSV/ΔNS2/Δ1313/I1314
a. Manufacturer:
Charles River Laboratories
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species for Licensed Use:
Human
e. Gene Engineering of F protein
  • Type: Gene mutation
  • Description: (Karron et al., 2020)Has a 523 nucleotide deletion of the NS2 gene. RSV/ΔNS2/Δ1313/I1314L was derived from a recombinant version of wt RSV strain A2 with the further modification of a 112 nucleotide phenotypically silent deletion in the SH noncoding sequence that stabilizes the complementary DNA (cDNA) during propagation in bacteria.
  • Detailed Gene Information: Click here.
f. Gene Engineering of F protein
  • Type: Codon deletion
  • Description: (Karron et al., 2020)A codon deletion in the L gene (Δ1313; deletion of S1313) plus the adjacent missense mutation I1314L that prevents the compensatory deattenuating mutation I1314T. RSV/ΔNS2/Δ1313/I1314L was derived from a recombinant version of wt RSV strain A2 with the further modification of a 112 nucleotide phenotypically silent deletion in the SH noncoding sequence that stabilizes the complementary DNA (cDNA) during propagation in bacteria.
  • Detailed Gene Information: Click here.
g. Immunization Route
Intramuscular injection (i.m.)
h. Storage
(Karron et al., 2020)CTM was stored at −70°C and diluted to dose on site using Leibovitz L15 medium.
i. Description
(Karron et al., 2020)RSV/ΔNS2/Δ1313/I1314L contains 2 attenuating elements: (1) deletion of the interferon antagonist NS2 gene and (2) deletion of codon 1313 of the RSV polymerase gene and the stabilizing missense mutation I1314L.
j. Human Response
  • Vaccination Protocol: (Karron et al., 2020) Children were given a dose of 10^6 PFU and in RSV-seronegative children at a dose of 10^5 or 10^6 PFU (Figure 1). Children were randomized 2:1 to receive vaccine or placebo, administered as nose drops
  • Side Effects: (Karron et al., 2020)In RSV-seropositive participants, URI was observed in 2 and cough was observed in 1 of 10 vaccinees during the 28-day postimmunization reporting period (Table 1); in each case, rhinovirus was detected in NW samples at the time of illness. None of the vaccinees shed vaccine virus, indicative of attenuation.
  • Efficacy: The vaccination showed statistically significant differences in log-fold plaque reduction neutralization antibody titers and the presence of 4-fold increase in RSV F IgG response in both seropositive and seronegative responses. However, 16/20 seropositive and 17/20 seronegative children in the placebo group did have RSV neutralizing antibody responses occured in 16 of 20 and F IgG responses in 17 of 20 RSV-seronegative children who received 106 PFU . For recipients of 105 and  106 PFU, the mean postvaccination PRNT was  1:37 and 1:64, respectively. (Karron et al., 2020)
20. rVSV-Gstem-RSV-F
a. Type:
Recombinant vector vaccine
b. Status:
Research
c. Host Species for Licensed Use:
None
d. Antigen
F protein (Johnson et al., 2013)
e. Preparation
Recombinant vesicular stomatitis virus (rVSV) replicon in which the attachment and fusion domains of the VSV glycoprotein (G) have been deleted (rVSV-Gstem)(Johnson et al., 2013)
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Vaccination Protocol: Mice were immunized on day 0. In studies that included a boost, mice were boosted at week 4(Johnson et al., 2013)
  • Challenge Protocol: RSV challenge virus was administered by the nasal route 4 weeks after the last immunization dose(Johnson et al., 2013)
  • Efficacy: (Johnson et al., 2013) A single high dose of the Gstem-RSV-F replicon was effective against challenge with both RSV A and B subgroup viruses. Finally, addition of an RSV glycoprotein (G)-expressing Gstem vector significantly improved the incomplete protection achieved with a single low dose of Gstem-RSV-F vector alone
21. VSV-RSV(F/G)
a. Type:
Recombinant vector vaccine
b. Status:
Licensed
c. Host Species for Licensed Use:
Mouse
d. Gene Engineering of G
  • Type: Recombinant protein preparation
  • Description: Since Gstem lacks the receptor binding and fusion domains, needs the G protein in trans (Johnson et al., 2013).
  • Detailed Gene Information: Click here.
e. Preparation
Recombinant vesicular stomatitis virus (rVSV) replicon in which the attachment and fusion domains of the VSV glycoprotein (G) have been deleted (rVSV-Gstem)(Johnson et al., 2013)
f. Immunization Route
Intramuscular injection (i.m.)
IV. References
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