Varicella zoster virus (VZV) is one of eight herpes viruses known to infect humans (and other vertebrates). Varicella zoster virus is known by many names, including: chickenpox virus, varicella virus, zoster virus, and human herpes virus type 3 (HHV-3). It commonly causes chicken-pox in children and both shingles and postherpetic neuralgia in adults. Primary VZV infection results in chickenpox (varicella). After clinical symptoms of chickenpox have resolved, VZV remains dormant in the nervous system of the infected person (virus latency). In about 10-20% of cases, VZV reactivates later in life producing a disease known as herpes zoster or shingles. Serious complications of shingles include postherpetic neuralgia, zoster multiplex, myelitis, herpes ophthalmicus, or zoster sine herpete (Wiki: Varicella zoster).
4. Microbial Pathogenesis
VZV share much genome homology with the herpes simplex viruses (HSV). The capsid is surrounded by a number of loosely associated proteins known collectively as the tegument. Many of these tegument proteins play critical roles in initiating the process of virus reproduction in the infected cell. The tegument is in turn covered by a lipid envelope studded with glycoproteins that are displayed on the exterior of the virion (Wiki: Varicella zoster).
II. Vaccine Related Pathogen Genes
1. ORF67
Gene Name :
ORF67
Sequence Strain (Species/Organism) :
Human alphaherpesvirus 3
Protein Note :
envelope glycoprotein I; the Herpesviridae are non-segmented dsDNA viruses with genomes ranging from 120-230kbp; although herpes viruses vary greatly in sequence identity and homology, they all share four common elements: an envelope, a tegument which is composed of viral enzymes, a capsid of 162 capsomers, and a core composed of genomic DNA;virion envelope glycoproteins bind to cellular receptors; envelope glycoprotein E and glycoprotein I form a heterodimer that play important roles in virus cell-to-cell spread
Molecule Role Annotation :
Monoclonal antibodies to gI neutralize VZV in vitro in a complement- dependent manner (Keller et al., 1986). Guinea pigs immunized with recombinant varicella-zoster virus (VZV) glycoproteins E (gE) and I (gI) developed antigen-specific antibodies in the sera, vitreous, and conjunctival washes. Sera from immunized animals neutralized both cell-free and cell-associated VZV, and peripheral blood lymphocytes proliferated in vitro in response to recombinant gE and gI and to antigens from VZV-infected cells. Immunized guinea pigs were inoculated intravitreally with VZV, which induces chronic uveitis. VZV DNA was more rapidly cleared and infectious VZV was isolated less frequently from the retinas of animals immunized with gE and gI compared with that in controls receiving adjuvant alone (Kimura et al., 1998).
Protein Note :
envelope glycoprotein E; the Herpesviridae are non-segmented dsDNA viruses with genomes ranging from 120-230kbp; although herpes viruses vary greatly in sequence identity and homology, they all share four common elements: an envelope, a tegument which is composed of viral enzymes, a capsid of 162 capsomers, and a core composed of genomic DNA;virion envelope glycoproteins bind to cellular receptors; envelope glycoprotein E and glycoprotein I form a heterodimer that play important roles in virus cell-to-cell spread
Molecule Role Annotation :
Monoclonal antibodies to gE neutralize VZV in vitro in a complement- dependent manner (Wu and Forghani, 1997). Guinea pigs immunized with recombinant varicella-zoster virus (VZV) glycoproteins E (gE) and I (gI) developed antigen-specific antibodies in the sera, vitreous, and conjunctival washes. Sera from immunized animals neutralized both cell-free and cell-associated VZV, and peripheral blood lymphocytes proliferated in vitro in response to recombinant gE and gI and to antigens from VZV-infected cells. Immunized guinea pigs were inoculated intravitreally with VZV, which induces chronic uveitis. VZV DNA was more rapidly cleared and infectious VZV was isolated less frequently from the retinas of animals immunized with gE and gI compared with that in controls receiving adjuvant alone (Kimura et al., 1998).
maintained at a temperature of 2° to 8°C (36° to 46°F) or colder.
m . Approved Age for Licensed Use
12 months to 12 years old
n. Contraindication
Vaccine should not be administered to anyone with a known history of anaphylactic reactions to neomycin, or to anyone with a history of hypersensitivity to gelatin or any other component of the vaccine (FDA: ProQuad).
o. Description
ProQuad is a sterile lyophilized preparation of (1) the components of M-M-R*II (Measles, Mumps and Rubella Virus Vaccine Live): Measles Virus Vaccine Live, a more attenuated line of measles virus, derived from Enders' attenuated Edmonston strain and propagated in chick embryo cell culture; Mumps Virus Vaccine Live, the Jeryl Lynn™ (B level) strain of mumps virus propagated in chick embryo cell culture; Rubella Virus Vaccine Live, the Wistar RA 27/3 strain of live attenuated rubella virus propagated in WI-38 human diploid lung fibroblasts; and (2) Varicella Virus Vaccine Live (Oka/Merck) refrigerator-stable formulation, the Oka/Merck strain of varicella-zoster virus propagated in MRC-5 cells (FDA: ProQuad).
p.
Human Response
Immune Response:
According to clinical trials, there were high levels of antibodies in 97.5% of those vaccinated after a single dose of Proquad (FDA: ProQuad).
Side Effects:
Side effects of vaccination include: injection site reactions, fever, irritability and diarrhea.
3. Varicella Subunit Vaccine encoding gI and gE glycoproteins
Vaccination Protocol:
Female Hartley guinea pigs (5 weeks old) were immunized with either a mixture of purified re- combinant gE and gI (25 μg each) or the recombinant gE-gI complex (50 μg). Purified protein solutions (0.25 mL) were injected intramuscularly with 0.25 mL of complete Freund's adjuvant at the first injection followed with incomplete Freund's adjuvant at the second and third injections at 2-week intervals. Control animals received 0.25 mL of PBS and an equal amount of adjuvant (Kimura et al., 1998).
Challenge Protocol:
To determine whether immunization with gE and gI can enhance the clearance of VZV in vivo, both immunized and control (adjuvant- alone) guinea pigs were challenged with VZV. Animals were inoculated intravitreally with 200 pfu of cell-associated VZV 4 weeks after the final immunization. At 4 h after inoculation, 4 animals from each group were sacrificed, and their eyes were harvested to test for infectious VZV (Kimura et al., 1998).
Efficacy:
In the gE-gI-immunized group, VZV was isolated from only 1 of 4 animals, and this animal had the lowest CMI and the lowest titer of anti-gE and anti-gI antibodies in the vitreous body. In contrast, VZV was isolated from 3 of 4 animals in the adjuvant-alone group (Kimura et al., 1998).
OkaIMerck strain of live, attenuated varicella vlrus.
k. Preparation
The OkaIMerck strain of live, attenuated varicella vlrus was initially obtained from a child with wild-type varicella, then introduced into human embryonic lung cell'cultures, adapted to and propagated in embryonic guinea pig cell cultures and finally propagated in human diploid cell cultures (WI-38). This live, attenuated varicella vaccine is a lyophllized preparation containing sucrose, phosphate, glutamate, processed gelatin, and urea as stabilizers. The product contains no preservative (FDA: Varivax).
l. Immunization Route
Intradermal injection (i.d.)
m. Storage
DO NOT FREEZE, store at 2 to 8°C or colder (36 to 46°F or colder).
n . Approved Age for Licensed Use
1 year and older
o. Contraindication
A history of hypersensitivity to any component of the vaccine, including gelatin (FDA: Varivax).
p. Description
Indication: For active immunization of persons 12 months of age and older.
q.
Human Response
Immune Response:
Clinical trials with several formulations of VARIVAX containing the attenuated virus ranging from 1000 to 50,000 PFU per dose, have demonstrated that VARIVAX induces detectable immune responses and is generally well tolerated in healthy individuals ranging from 12 months to 55 years of age. VARIVAX was also found to induce cell-mediated immune responses in vaccinees (FDA: Varivax).
Side Effects:
Side effects of vaccination were mostly injection site redness and pain.
Efficacy:
The majority of subjects who received the vaccine and were exposed to wild-type virus were either completely protected from chickenpox or developed a milder form of the disease. Clinical studies have demonstrated continued protection up to 10 years after vaccination. Also, a boost in antibody levels has been observed in vaccinees following exposure to wild-type varicella as well as following a second dose of the vaccine (FDA: Varivax).
ZOSTAVAX is a lyophilized preparation of live, attenuated varicella-zoster virus (Oka/Merck) to be reconstituted with sterile diluent to give a single dose suspension with a minimum of 19,400 PFU (plaque forming units) when stored at room temperature for up to 30 minutes (FDA: Zostavax).
l. Storage
ZOSTAVAX SHOULD BE stored FROZEN at an average temperature of -15°C (+5°F) or colder.
m . Approved Age for Licensed Use
60 years and older
n. Contraindication
Should not be administered to anyone with known anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine. The vaccine should also not be administered to women of child-bearing age or to pregnant women (FDA: Zostavax).
o. Description
Indication: Prevention of herpes zoster (shingles) in individuals 60 years of age and older when administered as a single-dose (FDA: Zostavax).
p.
Human Response
Side Effects:
The most common side effects reported included headache and injection site reactions (FDA: Zostavax).
Efficacy:
According to clinical studies, ZOSTAVAX significantly reduced the risk of developing zoster when compared with placebo. Vaccine efficacy for the prevention of herpes-zoster (HZ) was highest for those subjects 60-69
years of age and declined with increasing age (FDA: Zostavax).
5. Keller et al., 1986: Keller PM, Lonergan K, Neff BJ, Morton DA, Ellis RW. Purification of individual varicella-zoster virus (VZV) glycoproteins gpI, gpII, and gpIII and their use in ELISA for detection of VZV glycoprotein-specific antibodies. Journal of virological methods. 1986; 14(2); 177-188. [PubMed: 3021804].
6. Kimura et al., 1998: Kimura H, Wang Y, Pesnicak L, Cohen JI, Hooks JJ, Straus SE, Williams RK. Recombinant varicella-zoster virus glycoproteins E and I: immunologic responses and clearance of virus in a guinea pig model of chronic uveitis. The Journal of infectious diseases. 1998; 178(2); 310-317. [PubMed: 9697709].
8. Wu and Forghani, 1997: Wu L, Forghani B. Characterization of neutralizing domains on varicella-zoster virus glycoprotein E defined by monoclonal antibodies. Archives of virology. 1997; 142(2); 349-362. [PubMed: 9125048].
