VIOLIN: Vaccine Investigation and Online Information Network

Human metapneumovirus

Table of Contents

General Information
Vaccine Related Pathogen Genes
1. F (Protective antigen)
2. M (Protective antigen)
3. P (Protective antigen)
4. G protein (Virmugen)
5. M2-2 (Virmugen)
Vaccine Information
References

I. General Information

1. NCBI Taxonomy ID:

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).

II. Vaccine Related Pathogen Genes

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:

b. Type:

Live, attenuated vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

African green monkey

e. Gene Engineering of G protein

Type: Gene mutation
Description: This G protein is from Human metapneumovirus (Biacchesi et al., 2005).
Detailed Gene Information: Click here.

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:

b. Type:

Live, attenuated vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

African green monkeys

e. Gene Engineering of M2-2

Type: Gene mutation
Description: This M2-2 mutant is from Human metapneumovirus (Biacchesi et al., 2005).
Detailed Gene Information: Click here.

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, Rh�aume C, Carbonneau J, Lavigne S, Couture C, Hamelin M�, 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. M�s et al., 2016: M�s V, Rodriguez L, Olmedillas E, Cano O, Palomo C, Terr�n 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]