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
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).
>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).
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)
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].
