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Human metapneumovirus

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
  2. Vaccine Related Pathogen Genes
    1. F (Protective antigen)
    2. M (Protective antigen)
    3. P (Protective antigen)
    4. G protein (Virmugen)
    5. M2-2 (Virmugen)
  3. Vaccine Information
    1. Human metapneumovirus G protein mutant vaccine
    2. Human metapneumovirus HMPV-VLP F/GC-85473
    3. Human metapneumovirus HMPV-VLP FC-85473
    4. Human metapneumovirus HMPV-VLP FCan98-75
    5. Human metapneumovirus M2-2 mutant vaccine
  4. References
I. General Information
1. NCBI Taxonomy ID:
162145
2. Disease:
Respiratory tract infection
3. Introduction
Human metapneumovirus is a negative single-stranded RNA virus belonging to the Paramyxoviridae family. Compared to human respiratory syncytial virus, HMPV is less severe and occurs in slightly older children. It can lead to hospitalization in children, elderly, and immunocompromised individuals (Wiki: Metapneumovirus).
1. F
  • Gene Name : F
  • Sequence Strain (Species/Organism) : Human metapneumovirus
  • NCBI Protein GI : AAU12148
  • Other Database IDs : CDD:278924
  • Taxonomy ID : 162145
  • Protein Name : F protein
  • Protein pI : 7.26
  • Protein Weight : 19607.66
  • Protein Length : 252
  • Protein Note : Fusion glycoprotein F0; pfam00523
  • Protein Sequence : Show Sequence
    >AAU12148.1 F protein, partial [Human metapneumovirus]
    YTYVFTLEVGDVENLTCTDGPSLIKTELDLTKSALRELKTVSADQLAREEQIENPRQSRFVLGAIALGVA
    TAAAVTAGIAIAKTIRLESEVNAIKGALKQTNEAVSTLGNGVRVLATAVRELKEFVSKNLTSAINRNKCD
    IADLKMAVSFSQFNRRFLNVVRQFSDNAGITPAISLDLMTDAELARAVSYMPT
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation :
2. G protein
  • Gene Name : G protein
  • Sequence Strain (Species/Organism) : Human metapneumovirus CAN97-83
  • NCBI Protein GI : 75549950
  • Other Database IDs : CDD:118131
  • Taxonomy ID : 694067
  • Gene Strand (Orientation) : ?
  • Protein Name : Major surface glycoprotein G
  • Protein Length : 219
  • Protein Note : Attachment glycoprotein G; Membrane-bound glycoprotein; mG
  • Protein Sequence : Show Sequence
    >gi|75549950|sp|Q6WB94.1|VGLG_HMPVC RecName: Full=Major surface glycoprotein G; AltName: Full=Attachment glycoprotein G; AltName: Full=Membrane-bound glycoprotein; Short=mG
    MEVKVENIRAIDMLKARVKNRVARSKCFKNASLILIGITTLSIALNIYLIINYTIQKTSSESEHHTSSPP
    TESNKEASTISTDNPDINPNSQHPTQQSTENPTLNPAASVSPSETEPASTPDTTNRLSSVDRSTAQPSES
    RTKTKPTVHTRNNPSTASSTQSPPRATTKAIRRATTFRMSSTGKRPTTTSVQSDSSTTTQNHEETGSANP
    QASVSTMQN
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A G mutant is attenuated in African green monkeys and induces protection from challenge with wild type HMPV (Biacchesi et al., 2005).
  • Related Vaccine(s): Human metapneumovirus G protein mutant vaccine
3. M
  • Gene Name : M
  • Sequence Strain (Species/Organism) : Human metapneumovirus
  • NCBI Protein GI : CAD28609
  • Other Database IDs : CDD:281396
    GOA:Q80IJ6
    InterPro: IPR005056
    UniProtKB/TrEMBL: Q80IJ6
  • Taxonomy ID : 162145
  • Protein Name : matrix
  • Protein pI : 4.56
  • Protein Weight : 9995.7
  • Protein Length : 150
  • Protein Note : Pneumovirus matrix protein; pfam03393
  • Protein Sequence : Show Sequence
    >CAD28609.1 matrix, partial [Human metapneumovirus]
    YQGIPYTAAVQVDLIEKDLLPASLTIWFPLFQANTPPAVLLDQLKTLTITTLYAASQNGPILKVNASAQG
    AAMSVLPKKFEVNATVALDEYSKLE
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (Aerts et al., 2015)
4. M2-2
  • Gene Name : M2-2
  • Sequence Strain (Species/Organism) : Human metapneumovirus CAN97-83
  • NCBI Protein GI : 75549952
  • Taxonomy ID : 694067
  • Gene Strand (Orientation) : ?
  • Protein Name : Matrix protein M2-2
  • Protein Length : 71
  • Protein Note : Matrix protein M2-2. /FTId=PRO_0000394813.
  • Protein Sequence : Show Sequence
    >gi|75549952|sp|Q6WB96.1|M22_HMPVC RecName: Full=Matrix protein M2-2
    MTLHMPCKTVKALIKCSEHGPVFITIEVDEMIWTQKELKEALSDGIVKSHTNIYNCYLENIEIIYVKAYL
    S
  • Molecule Role : Virmugen
  • Molecule Role Annotation : An M2-2 mutant is attenuated in African green monkeys and induced protection from challenge with wild type HMPV (Biacchesi et al., 2005).
  • Related Vaccine(s): Human metapneumovirus M2-2 mutant vaccine
5. P
  • Gene Name : P
  • Sequence Strain (Species/Organism) : Human metapneumovirus
  • NCBI Protein GI : YP_012606
  • Other Database IDs : CDD:280615
  • Taxonomy ID : 162145
  • Protein Name : phosphoprotein
  • Protein pI : 4.54
  • Protein Weight : 32449.44
  • Protein Length : 352
  • Protein Note : Pneumovirus phosphoprotein; pfam02478
  • Protein Sequence : Show Sequence
    >YP_012606.1 phosphoprotein [Human metapneumovirus]
    MSFPEGKDILFMGNEAAKLAEAFQKSLRKPSHKRSQSIIGEKVNTVSETLELPTISRPTKPTILSEPKLA
    WTDKGGAIKTEAKQTIKVMDPIEEEEFTEKRVLPSSDGKTPAEKKLKPSTNTKKKVSFTPNEPGKYTKLE
    KDALDLLSDNEEEDAESSILTFEERDTSSLSIEARLESIEEKLSMILGLLRTLNIATAGPTAARDGIRDA
    MIGIREELIADIIKEAKGKAAEMMEEEMNQRTKIGNGSVKLTEKAKELNKIVEDESTSGESEEEEELKDT
    QENNQEDDIYQLIM
    
    
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : (O'Shaughnessy et al., 2011)
III. Vaccine Information
1. Human metapneumovirus G protein mutant vaccine
a. Vaccine Ontology ID:
VO_0002976
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
African green monkey
e. Gene Engineering of G protein
f. Immunization Route
intranasal immunization
g. Monkey Response
  • Persistence: A G protein mutant is attenuated in African green monkeys (Biacchesi et al., 2005).
  • Efficacy: A G protein mutant induces significant protection in African green monkeys from challenge with wild type HMPV (Biacchesi et al., 2005).
2. Human metapneumovirus HMPV-VLP F/GC-85473
a. Type:
Viral-like particles-based vaccine
b. Status:
Research
c. Host Species for Licensed Use:
None
d. Host Species as Laboratory Animal Model:
mouse
e. Antigen
Retroviral-based VLP F/GC-85473 displaying HMPV glycoproteins (Lévy et al., 2013)
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Description
Retroviral-based VLPs (virus like particles) displaying HMPV glycoproteins induced protection against homologous and heterologous HMPV challenge. (Lévy et al., 2013)
h. Mouse Response
  • Vaccination Protocol: Groups of 4–6-week-old BALB/c mice (Charles River Laboratories) were immunized by intraperitoneal injection with 100 µl of concentrated HMPV-VLPs incorporating FC-85473 , F/GC-85473 , FCan98-75, or no GP or with PBS. (Lévy et al., 2013)
  • Immune Response: Retroviral-derived VLPs incorporating F alone or in combination with G induced neutralizing antibody responses in mice. Maximal levels of neutralization could be reached after 2 consecutive injections. (Lévy et al., 2013)
  • Challenge Protocol: Mice were immunized with VLPs as described above or were infected intranasally with 0.8 × 10^6 TCID50 of either C-85473 or Can98-75 at each time. Twenty-one days after the last immunization, mice were infected intranasally with HMPV strain C-85473 (8 × 10^5 TCID50 /mouse) or Can98-75 (1 × 10^6 TCID50 ) (Lévy et al., 2013)
  • Efficacy: Infection by the Can98-75 strain led to 100% mortality by day 8 after challenge in control mice inoculated with PBS as well as with NoEnv-VLPs. In contrast, mice previously infected with the homologous virus, Can98-75, recovered and survived the challenge. Similarly, most mice immunized with HMPV-VLPs survived the challenge, indicating a cross-protection induced by immunization by VLPs harboring non-homologous F or F/G glycoproteins. Challenge with the C-85473 strain of HMPV was sub-lethal due to a slightly lower inoculum than that of Can98-75 virus, since mice immunized with PBS only or with NoEnv-VLPs exhibited profound weight loss yet with 67% survival by day 8 post-challenge. In contrast, mice previously immunized with the homologous virus, C-85473, or with homologous or het- erologous HMPV-VLPs exhibited partial weight loss and survived the challenge. (Lévy et al., 2013)
3. Human metapneumovirus HMPV-VLP FC-85473
a. Type:
Viral-like particles-based vaccine
b. Status:
Research
c. Host Species for Licensed Use:
None
d. Host Species as Laboratory Animal Model:
mouse
e. Antigen
Retroviral-based VLP FC-85473 displaying HMPV glycoproteins (Lévy et al., 2013)
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Description
Retroviral-based VLPs (virus like particles) displaying HMPV glycoproteins induced protection against homologous and heterologous HMPV challenge. (Lévy et al., 2013)
h. Mouse Response
  • Vaccination Protocol: Groups of 4–6-week-old BALB/c mice (Charles River Laboratories) were immunized by intraperitoneal injection with 100 µl of concentrated HMPV-VLPs incorporating FC-85473 , F/GC-85473 , FCan98-75, or no GP or with PBS. (Lévy et al., 2013)
  • Immune Response: Retroviral-derived VLPs incorporating F alone or in combination with G induced neutralizing antibody responses in mice. Maximal levels of neutralization could be reached after 2 consecutive injections. (Lévy et al., 2013)
  • Challenge Protocol: Mice were immunized with VLPs as described above or were infected intranasally with 0.8 × 10^6 TCID50 of either C-85473 or Can98-75 at each time. Twenty-one days after the last immunization, mice were infected intranasally with HMPV strain C-85473 (8 × 10^5 TCID50 /mouse) or Can98-75 (1 × 10^6 TCID50 ) (Lévy et al., 2013)
  • Efficacy: Infection by the Can98-75 strain led to 100% mortality by day 8 after challenge in control mice inoculated with PBS as well as with NoEnv-VLPs. In contrast, mice previously infected with the homologous virus, Can98-75, recovered and survived the challenge. Similarly, most mice immunized with HMPV-VLPs survived the challenge, indicating a cross-protection induced by immunization by VLPs harboring non-homologous F or F/G glycoproteins. Challenge with the C-85473 strain of HMPV was sub-lethal due to a slightly lower inoculum than that of Can98-75 virus, since mice immunized with PBS only or with NoEnv-VLPs exhibited profound weight loss yet with 67% survival by day 8 post-challenge. In contrast, mice previously immunized with the homologous virus, C-85473, or with homologous or het- erologous HMPV-VLPs exhibited partial weight loss and survived the challenge. (Lévy et al., 2013)
4. Human metapneumovirus HMPV-VLP FCan98-75
a. Type:
Viral-like particles-based vaccine
b. Status:
Research
c. Host Species for Licensed Use:
None
d. Host Species as Laboratory Animal Model:
mouse
e. Antigen
Retroviral-based VLP FCan98-75 displaying HMPV glycoproteins (Lévy et al., 2013)
f. Immunization Route
Intraperitoneal injection (i.p.)
g. Description
Retroviral-based VLPs (virus like particles) displaying HMPV glycoproteins induced protection against homologous and heterologous HMPV challenge. (Lévy et al., 2013)
h. Mouse Response
  • Vaccination Protocol: Groups of 4–6-week-old BALB/c mice (Charles River Laboratories) were immunized by intraperitoneal injection with 100 µl of concentrated HMPV-VLPs incorporating FC-85473 , F/GC-85473 , FCan98-75, or no GP or with PBS. (Lévy et al., 2013)
  • Immune Response: Retroviral-derived VLPs incorporating F alone or in combination with G induced neutralizing antibody responses in mice. Maximal levels of neutralization could be reached after 2 consecutive injections. (Lévy et al., 2013)
  • Challenge Protocol: Mice were immunized with VLPs as described above or were infected intranasally with 0.8 × 10^6 TCID50 of either C-85473 or Can98-75 at each time. Twenty-one days after the last immunization, mice were infected intranasally with HMPV strain C-85473 (8 × 10^5 TCID50 /mouse) or Can98-75 (1 × 10^6 TCID50 ) (Lévy et al., 2013)
  • Efficacy: Infection by the Can98-75 strain led to 100% mortality by day 8 after challenge in control mice inoculated with PBS as well as with NoEnv-VLPs. In contrast, mice previously infected with the homologous virus, Can98-75, recovered and survived the challenge. Similarly, most mice immunized with HMPV-VLPs survived the challenge, indicating a cross-protection induced by immunization by VLPs harboring non-homologous F or F/G glycoproteins. Challenge with the C-85473 strain of HMPV was sub-lethal due to a slightly lower inoculum than that of Can98-75 virus, since mice immunized with PBS only or with NoEnv-VLPs exhibited profound weight loss yet with 67% survival by day 8 post-challenge. In contrast, mice previously immunized with the homologous virus, C-85473, or with homologous or het- erologous HMPV-VLPs exhibited partial weight loss and survived the challenge. (Lévy et al., 2013)
5. Human metapneumovirus M2-2 mutant vaccine
a. Vaccine Ontology ID:
VO_0002977
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
African green monkeys
e. Gene Engineering of M2-2
f. Immunization Route
intranasal immunization
g. Monkey Response
  • Persistence: An M2-2 mutant is attenuated in African green monkeys (Biacchesi et al., 2005).
  • Efficacy: An M2-2 mutant induces significant protection in African green monkeys from challenge with wild type HMPV (Biacchesi et al., 2005).
IV. References
1. Aerts et al., 2015: Aerts L, Rhéaume C, Carbonneau J, Lavigne S, Couture C, Hamelin MÈ, Boivin G. Adjuvant effect of the human metapneumovirus (HMPV) matrix protein in HMPV subunit vaccines. The Journal of general virology. 2015; 96(Pt 4); 767-774. [PubMed: 25519171].
2. Biacchesi et al., 2005: Biacchesi S, Pham QN, Skiadopoulos MH, Murphy BR, Collins PL, Buchholz UJ. Infection of nonhuman primates with recombinant human metapneumovirus lacking the SH, G, or M2-2 protein categorizes each as a nonessential accessory protein and identifies vaccine candidates. Journal of virology. 2005; 79(19); 12608-12613. [PubMed: 16160190].
3. Más et al., 2016: Más V, Rodriguez L, Olmedillas E, Cano O, Palomo C, Terrón MC, Luque D, Melero JA, McLellan JS. Engineering, Structure and Immunogenicity of the Human Metapneumovirus F Protein in the Postfusion Conformation. PLoS pathogens. 2016; 12(9); e1005859. [PubMed: 27611367].
4. O'Shaughnessy et al., 2011: O'Shaughnessy L, Carr M, Crowley B, Carberry S, Doyle S. Recombinant expression and immunological characterisation of proteins derived from human metapneumovirus. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2011; 52(3); 236-243. [PubMed: 21920812].
5. Wiki: Metapneumovirus: Metapneumovirus [http://en.wikipedia.org/wiki/Metapneumovirus]