Measles virus is a negative strand RNA virus in the Morbillivirus genus of the Paramyxoviridae family. The virus was first isolated in 1954. Measles virus causes measles, a highly infectious disease of humans spread by the respiratory route and characterized by fever and rash. Important complications include secondary infections associated with MV-induced immune suppression and the neurological disease post-infectious encephalomyelitis (Griffin et al., 2008).
4. Microbial Pathogenesis
Measles virus (MV) has two envelope glycoproteins, the haemagglutinin (H) and fusion proteins, which are responsible for attachment and membrane fusion, respectively. Human signalling lymphocyte activation molecule (SLAM; also called CD150), a membrane glycoprotein of the immunoglobulin superfamily, acts as a cellular receptor for MV. SLAM is expressed on immature thymocytes, activated lymphocytes, macrophages and dendritic cells. It regulates production of interleukin (IL)-4 and IL-13 by CD4+ T cells, as well as production of IL-12, tumour necrosis factor alpha and nitric oxide by macrophages. The distribution of SLAM is in accord with the lymphotropism and immunosuppressive nature of MV (Yanagi et al., 2006).
5. Host Ranges and Animal Models
Humans are the only known natural host of measles, although the virus can infect some non-human primate species (Wiki: Measles).
6. Host Protective Immunity
Although innate responses probably contribute to control of virus replication during the incubation period, the onset of clinically apparent disease coincides with the appearance of MV-specific adaptive humoral and cellular immune responses. Antibody can protect from MV infection and may contribute to recovery from infection. Antibody is sufficient for protection because infants are protected by maternal antibody and passive transfer of immune serum can modify or interfere with measles vaccination and can partially protect children from measles after exposure. The best correlate of protection from infection is the level of neutralizing antibody. In infants, the level of maternal antibody correlates with failure of the humoral response to vaccination (Griffin et al., 2008).
Molecule Role Annotation :
Mice vaccinated with a vaccinia virus recombinant encoding the fusion protein of Measles virus developed measles neutralizing antibodies. The mice also resisted a normally lethal intracerebral inoculation of a cell-associated measles virus subacute sclerosing panencephalitis strain (Drillien et al., 1988).
Molecule Role Annotation :
Chimeric Venezuelan equine encephalitis/Sindbis virus (VEE/SIN) replicon particles were used to express the hemagglutinin (H) and fusion (F) proteins of measles virus (MV). When challenged with wild-type MV 12 to 17 months after vaccination, all vaccinated juvenile and infant monkeys vaccinated with VEE/SIN-H, VEE/SIN-H+F, and LAV were protected from rash and viremia (Pan et al., 2010).
>NP_056921.1 matrix protein [Measles morbillivirus]
MTEIYDFDKSAWDIKGSIAPIQPTTYSDGRLVPQVRVIDPGLGDRKDECFMYMFLLGVVEDSDPLGPPIG
RAFGSLPLGVGRSTAKPEELLKEATELDIVVRRTAGLNEKLVFYNNTPLTLLTPWRKVLTTGSVFNANQV
CNAVNLIPLDTPQRFRVVYMSITRLSDNGYYTVPRRMLEFRSVNAVAFNLLVTLRIDKAIGPGKIIDNAE
QLPEATFMVHIGNFRRKKSEVYSADYCKMKIEKMGLVFALGGIGGTSLHIRSTGKMSKTLHAQLGFKKTL
CYPLMDINEDLNRLLWRSRCKIVRIQAVLQPSVPQEFRIYDDVIINDDQGLFKVL
Molecule Role :
Protective antigen
Molecule Role Annotation :
Lewis rats were immunized with recombinant vaccinia virus (VV) expressing various proteins of measles virus (MV). VVM (Matrix Protein) -immunized rats were partially protected from MV challenge (Brinckmann et al., 1991).
Molecule Role Annotation :
Lewis rats were immunized with recombinant vaccinia virus (VV) expressing various proteins of measles virus (MV). VVN (Nucleocapsid Protein) -immunized rats survived a MV challenge infection (Brinckmann et al., 1991).
Molecule Role Annotation :
Lewis rats were immunized with recombinant vaccinia virus (VV) expressing various proteins of measles virus (MV). VVP (Phosphoprotein) -immunized rats were partially protected from MV challenge (Brinckmann et al., 1991).
Canarypox virus (CPV) recombinants expressing the hemagglutinin (HA) and fusion (F) glycoproteins of measles virus (MV) (Taylor et al., 1992).
h. Immunization Route
Intramuscular injection (i.m.)
i.
Dog Response
Vaccination Protocol:
Vaccinate the dogs with recombinant vaccine (Taylor et al., 1992).
Vaccine Immune Response Type:
VO_0003057
Challenge Protocol:
Lethal does of canine distember virus (CDV) (Taylor et al., 1992).
Efficacy:
The recombinants elicited a protective immune response. The level of MV neutralizing antibodies and the level of protection induced against CDV challenge achieved by the host-restricted CPV vector were equivalent to that obtained by vaccinia virus vectors expressing the same MV antigens (Taylor et al., 1992).
2. Canine Distemper-Adenovirus Type 2-Measles-Parainfluenza Modified Live Virus Vaccine (USDA: 1341.20)
Gelatin, Neomycin, Residual components of chick embryo cell cultures
j. Immunization Route
Subcutaneous injection
k. Description
Products: Live virus. Other components: Bovine serum, Glutamate, Yeast-derived, recombinant Human albumin, Residual protein, from cell culture, Sorbitol, Sucrose.
6. M-M-RVaxPro
a. Product Name:
Measles and Mumps Virus Vaccine, Live
b. Tradename:
M-M-RVaxPro
c. Manufacturer:
Merck and Co., Inc.
d. Type:
Live, attenuated vaccine
e. Status:
Licensed
f. Location Licensed:
USA
g. Host Species for Licensed Use:
Human
h. Allergen:
Gelatin, Eggs, Neomycin
i. Preparation
A lyophilised preparation of the live Oka strain varicella virus, with a potency of not less than 1350 plaque-forming units. Both vaccines were stored at 2°C to 8°C and reconstituted with sterile water for injections immediately before use. (Gillet et al., 2009)
j. Immunization Route
Intramuscular injection (i.m.)
k. Storage
Both vaccines were stored at 2°C to 8°C and reconstituted with sterile water for injections immediately before use. (Gillet et al., 2009)
l . Approved Age for Licensed Use
1 year and older
m. Description
M-M-RvaxPro is a lyophilised live virus vaccine manufactured with recombinant human albumin for vaccination against measles, mumps and rubella. (Gillet et al., 2009)
Vaccination Protocol:
Juvenile rhesus macaques were vaccinated with a single intradermal (i.d.) injection of 10^8 VEE/SIN-H particles or 108 VEE/SIN-H particles plus 3 x 10^6 VEE/SIN-F particles (VEE/SIN-H+F). Two juvenile monkeys were vaccinated with one dose of 5,000 PFU of the Moraten strain of LAV intramuscularly (i.m.). Two juvenile monkeys were vaccinated with three doses of 0.5 ml of FIMV i.m. at 0, 4, and 8 weeks. Three infant rhesus macaques were immunized i.d. with 10^8 VEE/SIN-H particles plus 3 x 10^6 VEE/SIN-F particles and boosted 2 months later (Pan et al., 2010)
Challenge Protocol:
For MV challenge, 10^4 tissue culture 50% infectious doses (TCID50) of the Bilthoven strain of MV were instilled intratracheally into anesthetized animals 12 to 17 months after vaccination. Monkeys were shaved and monitored frequently for development of a rash (Pan et al., 2010).
Efficacy:
Neutralizing antibody remained above the protective level for more than 1 year after vaccination with VEE/SIN-H, VEE/SIN-H+F, or LAV. When challenged with wild-type MV 12 to 17 months after vaccination, all vaccinated juvenile and infant monkeys vaccinated with VEE/SIN-H, VEE/SIN-H+F, and LAV were protected from rash and viremia, while FIMV-vaccinated monkeys were not (Pan et al., 2010).
Vaccination Protocol:
Juvenile rhesus macaques were vaccinated with a single intradermal (i.d.) injection of 10^8 VEE/SIN-H particles or 10^8 VEE/SIN-H particles plus 3 x 10^6 VEE/SIN-F particles (VEE/SIN-H+F). Two juvenile monkeys were vaccinated with one dose of 5,000 PFU of the Moraten strain of LAV intramuscularly (i.m.). Two juvenile monkeys were vaccinated with three doses of 0.5 ml of FIMV i.m. at 0, 4, and 8 weeks. Three infant rhesus macaques were immunized i.d. with 10^8 VEE/SIN-H particles plus 3 x 10^6 VEE/SIN-F particles and boosted 2 months later (Pan et al., 2010).
Challenge Protocol:
For MV challenge, 10^4 tissue culture 50% infectious doses (TCID50) of the Bilthoven strain of MV were instilled intratracheally into anesthetized animals 12 to 17 months after vaccination. Monkeys were shaved and monitored frequently for development of a rash (Pan et al., 2010).
Efficacy:
Neutralizing antibody remained above the protective level for more than 1 year after vaccination with VEE/SIN-H, VEE/SIN-H+F, or LAV. When challenged with wild-type MV 12 to 17 months after vaccination, all vaccinated juvenile and infant monkeys vaccinated with VEE/SIN-H, VEE/SIN-H+F, and LAV were protected from rash and viremia, while FIMV-vaccinated monkeys were not (Pan et al., 2010).
Host Gene Response of
IFNG
Gene Response:
VEE/SIN-H+F vaccinated rhesus macaques showed a significant increase in IFN-gamma producing cells in blood 1 to 2 weeks after vaccination as compared to the current live attenuated virus vaccine (LAV). The significant increase came after stimulation with the measles H-peptide (Pan et al., 2010).
Vaccination Protocol:
To determine the protective effect of individual measles virus (MV) proteins, 2- to 3-week-old suckling rats were immunized either once, twice or three times at 5 to 7 day intervals by i.p. injections of 10^7 p.f.u, of recombinant vaccinia virus (VV) expressing individual structural proteins or VV-wt (Brinckmann et al., 1991).
Challenge Protocol:
Three to 5 days after the last recombinant VV injection, the animals were challenged by intracerebral (i.c.) infection with the neurotropic rat brain-adapted MV strain CAM/RBH (0.5 × 10^4 to 8 x 10 ~ TCID50) (Brinckmann et al., 1991).
Efficacy:
Lewis rats were immunized with recombinant vaccinia virus (VV) expressing various proteins of measles virus (MV). VVM (Matrix Protein) -immunized rats were partially protected from MV challenge (Brinckmann et al., 1991).
Vaccination Protocol:
To determine the protective effect of individual measles virus (MV) proteins, 2- to 3-week-old suckling rats were immunized either once, twice or three times at 5 to 7 day intervals by i.p. injections of 10^7 p.f.u, of recombinant vaccinia virus (VV) expressing individual structural proteins or VV-wt (Brinckmann et al., 1991).
Challenge Protocol:
Three to 5 days after the last recombinant VV injection, the animals were challenged by intracerebral (i.c.) infection with the neurotropic rat brain-adapted MV strain CAM/RBH (0.5 × 10^4 to 8 x 10 ~ TCID50) (Brinckmann et al., 1991).
Efficacy:
Rats immunized with recombinant VVN survived a MV challenge infection (Brinckmann et al., 1991).
Vaccination Protocol:
To determine the protective effect of individual measles virus (MV) proteins, 2- to 3-week-old suckling rats were immunized either once, twice or three times at 5 to 7 day intervals by i.p. injections of 10^7 p.f.u, of recombinant vaccinia virus (VV) expressing individual structural proteins or VV-wt (Brinckmann et al., 1991).
Challenge Protocol:
Three to 5 days after the last recombinant VV injection, the animals were challenged by intracerebral (i.c.) infection with the neurotropic rat brain-adapted MV strain CAM/RBH (0.5 × 10^4 to 8 x 10 ~ TCID50) (Brinckmann et al., 1991).
Efficacy:
Lewis rats were immunized with recombinant vaccinia virus (VV) expressing various proteins of measles virus (MV). VVP (Phosphoprotein) -immunized rats were partially protected from MV challenge (Brinckmann et al., 1991).
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 98.9% 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.
V. References
1. Brinckmann et al., 1991: Brinckmann UG, Bankamp B, Reich A, ter Meulen V, Liebert UG. Efficacy of individual measles virus structural proteins in the protection of rats from measles encephalitis. The Journal of general virology. 1991; 72 ( Pt 10); 2491-2500. [PubMed: 1833505].
2. Drillien et al., 1988: Drillien R, Spehner D, Kirn A, Giraudon P, Buckland R, Wild F, Lecocq JP. Protection of mice from fatal measles encephalitis by vaccination with vaccinia virus recombinants encoding either the hemagglutinin or the fusion protein. Proceedings of the National Academy of Sciences of the United States of America. 1988; 85(4); 1252-1256. [PubMed: 3422488].
6. Gillet et al., 2009: Gillet Y, Habermehl P, Thomas S, Eymin C, Fiquet A. Immunogenicity and safety of concomitant administration of a measles, mumps and rubella vaccine (M-M-RvaxPro) and a varicella vaccine (VARIVAX) by intramuscular or subcutaneous routes at separate injection sites: a randomised clinical trial. BMC medicine. 2009; 7; 16. [PubMed: 19366435].
7. Griffin et al., 2008: Griffin DE, Pan CH, Moss WJ. Measles vaccines. Frontiers in bioscience : a journal and virtual library. 2008; 13; 1352-1370. [PubMed: 17981635].
10. Martinez et al., 1997: Martinez X, Brandt C, Saddallah F, Tougne C, Barrios C, Wild F, Dougan G, Lambert PH, Siegrist CA. DNA immunization circumvents deficient induction of T helper type 1 and cytotoxic T lymphocyte responses in neonates and during early life. Proceedings of the National Academy of Sciences of the United States of America. 1997; 94(16); 8726-8731. [PubMed: 9238045].
11. Pan et al., 2010: Pan CH, Greer CE, Hauer D, Legg HS, Lee EY, Bergen MJ, Lau B, Adams RJ, Polo JM, Griffin DE. A chimeric alphavirus replicon particle vaccine expressing the hemagglutinin and fusion proteins protects juvenile and infant rhesus macaques from measles. Journal of virology. 2010; 84(8); 3798-3807. [PubMed: 20130066].
12. Spreng et al., 2000: Spreng S, Gentschev I, Goebel W, Weidinger G, ter Meulen V, Niewiesk S. Salmonella vaccines secreting measles virus epitopes induce protective immune responses against measles virus encephalitis. Microbes and infection / Institut Pasteur. 2000; 2(14); 1687-1692. [PubMed: 11137042].
14. Yanagi et al., 2006: Yanagi Y, Takeda M, Ohno S. Measles virus: cellular receptors, tropism and pathogenesis. The Journal of general virology. 2006; 87(Pt 10); 2767-2779. [PubMed: 16963735].
