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Human coxsackievirus |
| Table of Contents |
- General Information
- NCBI Taxonomy ID
- Introduction
- Vaccine Related Pathogen Genes
- VP1
(Protective antigen)
- Vaccine Information
- Coxsackievirus DNA vaccine pCMV/VPl encoding VP1
- Coxsackievirus Inactivated Vaccine CV-A5
- References
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| I. General Information |
| 1. NCBI Taxonomy ID: |
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12066 |
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2. Introduction |
Coxsackie virus is a member of the Picornaviridae family of viruses in the genus termed enterovirus. Coxsackie viruses are subtype members of enterovirus that have a single strand of ribonucleic acid (RNA) for its genetic material. The enteroviruses are also referred to as picornaviruses (pico means "small," so, "small RNA viruses"). Coxsackie virus was first isolated from human feces in the town of Coxsackie, New York, in 1948 by G. Dalldorf. Coxsackie virus is also written as coxsackievirus in some publications.
Coxsackie viruses are separable into two groups, A and B, which are based on their effects on newborn mice (Coxsackie A results in muscle injury, paralysis, and death; Coxsackie B results in organ damage but less severe outcomes.) There are over 24 different serotypes of the virus (having distinct proteins on the viral surface). Coxsackie viruses infect host cells and cause host cells to break open (lyse).
Type A viruses cause herpangina (painful blisters in the mouth, throat, hands, feet, or in all these areas). Hand, foot, and mouth disease (HFMD) is the common name of this viral infection. Coxsackie A 16 (CVA16) causes the majority of HFMD infections in the U.S. It usually occurs in children (age 10 and under), but adults can also develop the condition. This childhood disease should not be confused with the "foot and mouth disease" usually found in animals with hooves (for example, cattle, pigs, and deer). Type A also causes conjunctivitis (inflammation of the eyelids and white area of the eye).
Type B viruses cause epidemic pleurodynia (fever, lung, and abdominal pain with headache that lasts about two to 12 days and resolves). Pleurodynia is also termed Bornholm disease. There are six serotypes of Coxsackie B (1-6, with B 4 considered by some researchers as a possible cause of diabetes in a number of individuals).
Both types of viruses (A and B) can cause meningitis, myocarditis, and pericarditis, but these occur infrequently from Coxsackie infections. Some researchers suggest Coxsackie virus (mainly Coxsackie B4) has a role in the development of acute onset type I (formerly known as juvenile) diabetes, but this relationship is still under investigation.
Coxsackie viruses and other enteroviruses may cause the childhood disease of hand, foot, and mouth disease. However, the majority of children with Coxsackie virus infections completely resolve the symptoms and infection in about 10-12 days. Recently (July 2012), in Asia (particularly Cambodia), children suspected to be infected with enterovirus 71 had a 90% mortality. This epidemic (mainly in babies, toddlers, and children under 2 years of age) is still under intense investigation and it is likely researchers will have a better understanding of this high death rate linked to enterovirus 71 soon. If enterovirus 71 is ultimately found responsible for these deaths, it is likely the virus has developed a new lethal ability to rapidly infect and destroy children's lung tissue. However, the research is ongoing and some investigators suggests that the children are dying from a combination of enterovirus 71, Streptococcus suis, and dengue viral coinfections (MedicineNet - Coxsackievirus). |
| II. Vaccine Related Pathogen Genes |
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1. VP1 |
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Gene Name :
VP1
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Sequence Strain (Species/Organism) :
Human coxsackievirus B3
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NCBI Protein GI :
254973291
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Other Database IDs :
CDD:278501
CDD:119412
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Taxonomy ID :
12072
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Gene Strand (Orientation) :
?
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Protein Name :
VP1
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Protein pI :
8.88
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Protein Weight :
29963.04
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Protein Length :
335
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Protein Note :
picornavirus capsid protein; pfam00073
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Protein Sequence : Show Sequence
>ACT98478.1 VP1, partial [Coxsackievirus B3]
GPVEDAVTAAIGRVADTVGTGPTNSEAIPALTAAETGHTSQVVPGDTMQTRHVKNYHSRSESTVENFLCR
SACVYFTEYENSGSKRYAEWVVTTRQAAQLRRKLEFFTYIRFDLELTFVITSTQQPSTTQNQDAQILTHQ
IMYVPPGGPVPDKVDSYAWQTSTNPSVFWTEGNAPPRMSIPFLSIGNAYSNFYDGWSEFSRNGVYGINTL
NNMGTLYARHVNTGSTGPIKSTIRIYFKPKHVKAWIPRPPRLCQYEKAKNVNFQPSGVTTTRQSITAMTN
TGAF
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Molecule Role :
Protective antigen
- Related Vaccine(s):
Coxsackievirus DNA vaccine pCMV/VPl encoding VP1
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| III. Vaccine Information |
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1. Coxsackievirus DNA vaccine pCMV/VPl encoding VP1 |
| a. Vaccine Ontology ID: |
| VO_0004361 |
| b. Type: |
| DNA vaccine |
| c. Status: |
| Research |
| d. Host Species as Laboratory Animal Model: |
| Macaque |
| e. Gene Engineering of
VP1 |
- Type:
DNA vaccine construction
- Description:
Vector pIRES expressed major structural protein (capsid protein VP1) VP1 of coxsackievirus B3 (CVB3) (Henke et al., 2004).
- Detailed Gene Information: Click here.
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| f. Vector: |
| pIRES (Henke et al., 2004) |
| g. Immunization Route |
| Intramuscular injection (i.m.) |
| h.
Mouse Response |
- Vaccine Immune Response Type:
VO_0000286
- Efficacy:
DNA immunizations with the major structural protein VP1 of coxsackievirus B3 (CVB3) have been previously found to protect mice from a lethal challenge with CVB3. Co-expression of the immune-stimulatory interleukin-2 (IL-2) can increase the efficacy of the inoculated DNA vaccine depending on the route of administration and the mouse strain used. After i.m. administration, IL-2 co-expression increased the protection rate by 18.3% whereby the g.g. inoculation was much less effective in BALB/c mice. In contrast, after g.g. inoculation IL-2 co-expression increased the protection rate by 36.7% whereby the i.m. was much less effective in C57BL/6 mice (Henke et al., 2004).
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2. Coxsackievirus Inactivated Vaccine CV-A5 |
| a. Type: |
| Inactivated or "killed" vaccine |
| b. Status: |
| Research |
| c. Host Species for Licensed Use: |
| None |
| d. Antigen |
| Coxsackievirus A5 (Jin et al., 2021) |
| e. Preparation |
| In an outbreak of HFMD in Xiangyang, China, in 2017, rectal swabs from patients were obtained. CV-A5-3487 was isolated in both RD and Vero cells and grown to titers higher than 1 × 10^8 50% cell culture infectious doses (CCID50)/ml. A Vero cell isolate, CV-A5-vN20, was selected as a vaccine candidate. Vero cells in a 10-layer cell factory were infected with CV-A5-vN20 at a multiplicity of infection (MOI) of 0.001. The harvest was purified through two steps of ultracentrifugation. (Jin et al., 2021) |
| f. Immunization Route |
| Intraperitoneal injection (i.p.) |
| g. Description |
| Vero cell-adapted CV-A5 strain is a promising vaccine candidate and could be used as a multivalent HFMD vaccine component in the future. (Jin et al., 2021) |
| h.
Mouse Response |
- Vaccination Protocol:
A group of 3-day-old mice were primed and boosted on day 10 through the i.p. route (Jin et al., 2021)
- Immune Response:
Levels of NtAb titers in sera on days 0, 14, and 28 were determined, representing those of preimmunization, postboost, and postchallenge antisera. In suckling mice, NtAbs were detectable only after boosting (day 14), and the seroconversion rate was 100%. NtAb titers increased dramatically after challenge (day 28, P < 0.001), reflecting strong immune responses following challenge. The results demonstrated that NtAb levels correlated with the survival of immunized mice, and there were no differences in titers of different antigen groups. (Jin et al., 2021)
- Challenge Protocol:
A group of 3-day-old mice were challenged 4 days later (once antibody levels had increased) with CV-A5-M14 at a dose of 10 LD50 (2 × 10^6 CCID50/mouse). (Jin et al., 2021)
- Efficacy:
All mice in the immunized groups survived after 14 days of observation, showing 100% protection, while all mice in the mock-immunized group died at 6 days postchallenge. (Jin et al., 2021)
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| IV. References |
1. Henke et al., 2004: Henke A, Chiang CS, Zell R, Stelzner A. Co-expression of interleukin-2 to increase the efficacy of DNA vaccine-mediated protection in coxsackievirus B3-infected mice. Antiviral research. 2004; 64(2); 131-136. [PubMed: 15498609].
2. MedicineNet - Coxsackievirus: Coxsackie Virus [http://www.medicinenet.com/coxsackie_virus/article.htm]
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