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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. F protein (Protective antigen)
    2. G protein (Protective antigen)
    3. M2-2 (Virmugen)
  3. Vaccine Information
    1. HDAd-sFsyn
    2. HRSV DNA vaccine DRF-412
    3. HRSV DNA vaccine pND-G
    4. Human Respiratory Syncytial Virus M2-2 mutant vaccine
  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
  • Gene Name : F protein
  • Sequence Strain (Species/Organism) : Human respiratory syncytial virus A
  • NCBI Protein GI : 306438651
  • Other Database IDs : CDD:189585
    GOA:E0WLR1
    InterPro: IPR000776
    UniProtKB/TrEMBL: E0WLR1
  • Taxonomy ID : 208893
  • Gene Strand (Orientation) : ?
  • Protein Name : F protein
  • Protein Length : 166
  • Protein Note : Fusion glycoprotein F0; pfam00523
  • Protein Sequence : Show Sequence
    >gi|306438651|emb|CBW45366.1| F protein [Human respiratory syncytial virus A]
    MELPILKTNAITTIFAAVTLCFASSQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCN
    GTDAKVKLIKQELDKYKNAVTELQLLMQSTPAANNRARRELPRFMNYTLNNTKNNNVTLSKKRKRRFLGF
    LLGVGSAIASGIAVSKVLHLEGEVNK
  • Molecule Role : Protective antigen
  • Related Vaccine(s): HRSV DNA vaccine DRF-412
2. G protein
  • Gene Name : G protein
  • Sequence Strain (Species/Organism) : Human respiratory syncytial virus A strain Long
  • NCBI Protein GI : 1353203
  • Other Database IDs : CDD:144411
  • Taxonomy ID : 11260
  • Gene Strand (Orientation) : ?
  • Protein Name : Major surface glycoprotein G
  • Protein Length : 298
  • Protein Note : Attachment glycoprotein G; Membrane-bound glycoprotein; mG
  • Protein Sequence : Show Sequence
    >gi|1353203|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
  • Related Vaccine(s): HRSV DNA vaccine pND-G
3. 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): Human Respiratory Syncytial Virus M2-2 mutant vaccine
III. Vaccine Information
1. 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.)
2. 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).
3. 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 protein
  • 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).
4. 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).
IV. References
1. Fu et al., 2014: Fu YH, Jiao YY, He JS, Giang GY, Zhang W, Yan YF, Ma Y, Hua Y, Zhang Y, Peng XL, Shi CX, Hong T. Sublingual administration of a helper-dependent adenoviral vector expressing the codon-optimized soluble fusion glycoprotein of human respiratory syncytial virus elicits protective immunity in mice. Antiviral research. 2014; 105; 72-79. [PubMed: 24560779].
2. Jin et al., 2003: Jin H, Cheng X, Traina-Dorge VL, Park HJ, Zhou H, Soike K, Kemble G. Evaluation of recombinant respiratory syncytial virus gene deletion mutants in African green monkeys for their potential as live attenuated vaccine candidates. Vaccine. 2003; 21(25-26); 3647-3652. [PubMed: 12922094].
3. Miller et al., 2002: Miller M, Cho JY, Baek KJ, Castaneda D, Nayar J, Rodriguez M, Roman M, Raz E, Broide DH. Plasmid DNA encoding the respiratory syncytial virus G protein protects against RSV-induced airway hyperresponsiveness. Vaccine. 2002; 20(23-24); 3023-3033. [PubMed: 12126916].
4. Wiki: Human respiratory syncytial virus: Human respiratory syncytial virus [http://microbewiki.kenyon.edu/index.php/Human_respiratory_syncytial_virus]
5. Wu et al., 2009: Wu H, Dennis VA, Pillai SR, Singh SR. RSV fusion (F) protein DNA vaccine provides partial protection against viral infection. Virus research. 2009; 145(1); 39-47. [PubMed: 19540885].