J Virol. 2010 Jan;84(1):119-30. The rubella virus capsid protein inhibits mitochondrial import. Ilkow CS, Weckbecker D, Cho WJ, Meier S, Beatch MD, Goping IS, Herrmann JM, Hobman TC. Source Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Abstract The rubella virus (RV) capsid is an RNA-binding protein that functions in nucleocapsid assembly at the Golgi complex, the site of virus budding. In addition to its role in virus assembly, pools of capsid associate with mitochondria, a localization that is not consistent with virus assembly. Here we examined the interaction of capsid with mitochondria and showed that this viral protein inhibits the import and processing of mitochondrial precursor proteins in vitro. Moreover, RV-infected cells were found to contain lower intramitochondrial levels of matrix protein p32. In addition to inhibiting the translocation of substrates into mammalian mitochondria, capsid efficiently blocked import into yeast mitochondria, thereby suggesting that it acts by targeting a highly conserved component of the translocation apparatus. Finally, mutation of a cluster of five arginine residues in the amino terminus of capsid, though not interfering with its binding to mitochondria, abrogated its ability to block protein import into mitochondria. This is the first report of a viral protein that affects the import of proteins into mitochondria.
As I child I received all the recommended vaccines that were out. (My mother has stated now, that had she known then what she does now though, that would not have happened), but anyway......
When I was 22 I delivered my son. While pregnant they ran all the blood tests that are done and discovered I was Rubella Non-immune. So before I left the hosp, they said I HAD to have my Rubella shot. (yes, I know better now). Also told me NOT to be around anyone that was pregnant for at least 3 days.
4 years later I was again pregnant. All the same blood tests were run and guess what? I was Rubella Non-immune. Again. Did it not work? Did it wear off? Who knows. But the tests revealed that I was
8 months later my dh and I took the kids to my parents for a visit. When we arrived we noticed a rash on my daughter. We thought maybe a heat rash from sitting in the car seat while we traveled? The next day my daughter was running a fever and was a bit cranky, but other than that she was fine. The rash lasted about 3-4 days, the fever about 2. When we got home, I checked Mendelsohn's book (How To Raise A Healthy Child In Spite OF Your Doctor) as well as asked her pediatrician and found out she'd had Rubella. Other than the rash, fever and a bit of crankiness, we had survived. HMMMM , and I never got it, yet I was supposedly Non-Immune? Makes ya wonder.
REPROTOX ® Database
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Last Updated: January 01, 2000
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GERMAN MEASLES VACCINE (NONE)
Rubella vaccine contains live, attenuated rubella (German measles) virus from the RA 27/3 strain of this virus. Each 0.5 mL dose of the reconstituted vaccine also contains 25 mcg of neomycin (Agent 1376) (1). Before January 1979 vaccines containing other strains of the rubella virus were in use (e.g. Cendehill, HPV-77), but the RA 27/3 vaccine has been shown to produce a greater variety of antibodies and an immunologic response that more closely resembles that induced by natural rubella infection. A small number of women (about 2%) do not respond with sufficient antibody production after vaccination to develop immunity (25).
A number of instances of first trimester rubella vaccination have been reported without adverse effects (2-6). In a summary of such reports made to the Centers for Disease Control, 210 women who were susceptible to a rubella infection and received a rubella vaccination within three months of their date of conception, gave birth to 212 normal infants (two women had twins) (6). Serologic evidence of subclinical rubella infection was found in approximately 2% of the infants whose mothers had been vaccinated within three months of conception (6). Two infants were born with asymptomatic glandular hypospadias, but, based on serologic tests, neither child showed evidence of significant exposure to rubella virus.
The collected data from the US, Germany, and the United Kingdom indicate that, at this time, the observed risk of congenital rubella syndrome (CRS) following rubella vaccination is zero. Because this observation is based on only a few hundred cases, a risk of vaccination induced CRS as high as 2% is still a statistical possibility, however the overall maximum risk remains far less than the 20% or greater risk of CRS associated with a first trimester maternal infection with wild rubella virus (1). Because of the uncertainties about possible adverse effects of live virus vaccination, the American College of Obstetricians and Gynecologists considers rubella vaccination contraindicated during pregnancy (19).
Reinfection with rubella may occur in as many as 80% of vaccinated subjects, but only in about 3% of those who have had a previous rubella infection (25). The risk of fetal infection after rubella reinfection in early pregnancy has been estimated to be less than 5% (26), which is comparable to the risk of any adverse outcome in a pregnancy. The administration of rubella vaccine during lactation often results in the excretion of live virus in the breast milk (7-10). Exposure to rubella virus before 15 months of age, whether from vaccination with live attenuated virus (11) or through the breast milk (10), can impair subsequent immunologic responsiveness to rubella vaccination (10-12). Although this impairment of the immune response to rubella vaccine has been clearly demonstrated, data are not available to determine whether the early exposure to rubella virus results in an increased susceptibility to rubella infection in later life (13). At present, the exposure of infants less than 15 months to rubella vaccine is only recommended for infants at high risk of incurring natural rubella infection (14). Because breastfeeding subsequent to rubella vaccination will often expose a neonate to rubella virus, vaccination of nursing women may not be ideal. At this time, however, clinical opinions vary on the advisability of vaccination during breastfeeding, because it is not clear that subclinical exposure to rubella virus during infancy significantly increases rubella susceptibility or morbidity in later life (12,13). Despite a large number of postpartum rubella vaccinations, there are only two case reports that suggest an infant may have developed a clinical rubella infection due to the virus in breast milk (15-17). Thus, this route of virus exposure is not likely to result in clinical disease in the infant.
Although acute and persistent forms of arthritis are more common after natural rubella infections (23), approximately 13% to 15% of the subjects receiving rubella vaccine will experience acute arthritis and arthralgias (20,24). A possible association with chronic arthritis is still under investigation (21). There is no evidence that the incidence of maternal arthropathy following rubella immunization is significantly higher during the postpartum period (12).
A young semen donor who was immunized with live attenuated rubella virus to satisfy a medical requirement at his university, developed bilateral testicular pain eight days later (18). A subsequent semen specimen was grossly abnormal, including both red and white blood cells. Sperm count and sperm motility were also reduced in comparison with previous specimens. Genital tenderness resolved rapidly. Semen quality returned to preimmunization levels over the following two months (18). Although testicular pain sometimes accompanies an active rubella infection, it has not been commonly noted after rubella vaccine.
McEvoy GK (ed): Drug Information 97, American Hospital Formulary Service, American Society of Hospital Pharmacists, Bethesda, MD. 1997. pp. 2645.
Bolognese RJ et al: Evaluation of possible transplacental infection with rubella vaccination during pregnancy. Am J Obstet Gynecol 117:939-41, 1973.
Ebbin AJ et al: Inadvertent rubella vaccination in pregnancy. Am J Obstet Gynecol 117:505-12, 1973.
Modlin JF et al: A review of five years experience with rubella vaccine in the United States. Pediatrics 55:20-9, 1975.
Preblud SR et al: Fetal risk associated with rubella vaccine. JAMA 246:1413-7, 1981.
Centers for Disease Control, U.S. Dept of Health and Human Services: Rubella vaccination during pregnancy - United States, 1971-1988. MMWR 38:289-93, 1989.
Isacson P et al: comparative study of live, attenuated rubella virus vaccines during the immediate puerperium. Obstet Gynecol 37:332-7, 1971.
Grillner L et al: Vaccination against rubella of newly delivered women. Schand J Infect Dis 5:237-41, 1973.
Buimovici-Klein E et al: Isolation of rubella virus in milk after postpartum immunization. J Pediatr 91:939-41, 1977.
Losonsky GA et al: Effect of immunization against rubella on lactation products. I. Development and characterization os specific immunologic reactivity in breast milk. J Infect Dis 145:654-60, 1982.
Wilkins J, Wehrle PF: Additional evidence against measles vaccine administered to infants less than 12 months of age: altered immune response following active/passive immunization. J Pediatr 94:865-9, 1979.
Tingle AJ: Postpartum rubella immunization, reply. J Infect Dis 154:368-9, 1986.
Preblud S et al: Postpartum Rubella Immunization. J Inf Dis 154:367-8, 1986.
Fulginiti V: Commentary: Measles immunization. J Pediatr 94:1019-20, 1979.
Landes RD et al: Neonatal rubella following postpartum maternal immunization. J Pediatr 97:465-7, 1980.
Lerman SJ: Neonatal rubella following maternal immunization. J Pediatr 98:668, 1981.
Bass JW, Landes RD: Neonatal rubella following maternal immunization. Reply. J Pediatr 98:668-9, 1981.
Zeffer KB, Sauer MV: Orchitis after a rubella vaccination. J Reprod Med 33:80-1, 1988.
American College of Obstetricians and Gynecologists: ACOG Technical Bulletin No. 160, October 1991.
Institute of Medicine: Adverse effects of pertuss and rubella vaccines. Washington, DC, National Academy Press, 1991.
Geier MR: Rubella vaccination [letter; comment]. Fertil Steril 1992; 57: 229.
Slater PE, Ben-Zvi T, Fogel A, Ehrenfeld M, Ever-Hadani S: Absence of an association between rubella vaccination and arthritis in underimmune postpartum women. Vaccine 13:1529-32, 1995.
Tingle AJ, Allen M, Petty RE, Kettyls GD, Chantler JK: Rubella-associated arthritis: comparative study of joint manifestations associated with natural rubella infection and RA27/3 rubella immunisation. Ann Rheum Dis 45:110-4, 1986.
Tingle AJ, Mitchell LA, Grace M et al: Randomised double- blind placebo-controlled study on adverse effects of rubella immunisation in seronegative women. Lancet 349:1277-81, 1997.
Burgess MA: Rubella reinfection--what risk to the fetus? Med J Aust 1992;156:824-5.
Morgan-Capner P, Miller E, Vurdien JE, Ramsay MEB: Outcome of pregnancy after maternal reinfection with rubella. Commun Dis Rep 1991; 1:R57-R59.
Sunday, April 06, 2003
An unfounded association is risking children's health
Latest studies show no link between vaccinations and autism By PETER HOTEZ
AS A PEDIATRICIAN, vaccine researcher and the father of an autistic child, I have great concerns regarding the debate about the safety of our infant and childhood vaccines. The unfounded association that has been proposed by some between vaccines and autism is at best misleading and at worst a serious undermining of children's health.
The vaccine/autism question stems from two separate theories that are unscientific and have been determined to be invalid by the qualified experts in vaccine science. The first claims autism is the result of the combination measles, mumps, rubella (MMR) vaccine. The second claims thimerosal is the autism culprit. Thimerosal is a mercury-based compound that was used in many vaccines since the 1930s, but MMR vaccine does not, and has never, contained thimerosal.
Let's begin with the MMR question. Numerous large-scale studies have shown no increase in autism for children who received the MMR vaccine. The most recent study, published in The New England Journal of Medicine and funded by the National Alliance for Autism Research, examined more than 500,000 Danish children. The study found there was no greater incidence of autism among children who received the MMR vaccine than those who did not.
Scientific organizations including the Centers for Disease Control, the Institute of Medicine and the American Academy of Pediatrics have all said that the scientific evidence does not support a causal link between MMR and autism. Ironically, the only known cause of autism is rubella, which the MMR vaccine prevents.
The second vaccine/autism theory is based on the idea that autism is the result of mercury poisoning from the thimerosal in vaccines. In 1999, public health officials decided that thimerosal should be removed from vaccines as a precautionary measure.
A study on thimerosal conducted by the University of Rochester was published last fall in the British medical journal The Lancet. The study showed that ethyl mercury - which is what thimerosal becomes as it is metabolized - is excreted from the body within seven days and does not appear to build up from one vaccination to the next. Even when it is still in the body following immunization, the levels of this mercury do not exceed the government standard, which is based on a more potentially harmful form of mercury known as methyl mercury - the type found in some types of fish. When the report was released, researchers wrote that children would likely be exposed to more mercury by eating a tuna fish sandwich than by vaccines.
More research into thimerosal is under way, though if thimerosal were the cause of what some believe is a dramatic increase in the incidence of autism, one would expect the incidence to drop dramatically since the removal of thimerosal from vaccines in 1999. But it hasn't. As the father of a child with autism, I know the need for parents to understand the root of this heartbreaking disorder and find something to blame. However, as a medical doctor, I believe a more constructive focus is on advancing treatment options, extending reimbursement policies and finding a cure.
By focusing on unproved theories, we not only risk wasting our precious resources and not finding the real cause of autism, but we also risk parents losing confidence in vaccines, resulting in fewer children being immunized. This would leave our youngest vulnerable to diseases that we have only read about in history books, reversing one of the world's most successful public health programs.
A proposed link between autism and vaccines is a distraction that focuses attention away from the real needs of parents of autistic children, namely finding respite care, searching for a child psychiatrist who accepts health insurance, and getting quality special education through public school systems. Ireland and parts of the United Kingdom are a case study of what happens when the fear spreads through the media; fears of the "MMR jab" have led to a significant drop in the immunization rate, resulting in a dramatic increase in the number of measles and mumps cases. We often forget that measles is still the single leading killer of children in the world. With today's ease of travel, these diseases can quickly be imported into the United States, putting children who are unprotected at great risk of contracting the disease.
Every parent has to decide: Is it worth protecting my child from a real, deadly threat or protecting him from a hypothetical, scientifically unproven leap of logic? I chose the former, and I am confident I made the right decision.
PETER HOTEZ is chairman of the Department of Microbiology and Tropical Medicine at George Washington University. He also is a senior fellow and chairman of the Sabin Vaccine Institute's Scientific Advisory Council. KNIGHT RIDDER/TRIBUNE
Cytokine profile after rubella vaccine inoculation: evidence of the immunosuppressive effect of vaccination.
Pukhalsky AL, Shmarina GV, Bliacher MS, Fedorova IM, Toptygina AP, Fisenko
JJ, Alioshkin VA.
Research Centre for Medical Genetics 1 Moskvorechie Street 115478 Moscow.
Background and aim Immunization with live virus vaccines may cause an immunosuppression with lymphopaenia, impaired cytokine production and defective lymphocyte response to mitogenes. These abnormalities were described in subjects vaccinated against measles. This study was performed to analyse the host immune response related to immunosuppression in subjects vaccinated with live attenuated rubella vaccine. Methods Eighteen schoolgirls, aged 11-13 years, were vaccinated with live attenuated rubella vaccine Rudivax((R)). Before immunization, and 7 and 30 days after, peripheral blood was collected. Cellular fractions were subjected to flow cytometric analysis, and the lymphocyte response to phytohaemagglutinin was investigated. Plasma samples were analysed for cytokines (interleukin (IL)-4 IL-10, tumour necrosis factor-alpha, and interferon-gamma) by enzyme-linked immunosorbent assay techniques. Results On day 7 after vaccination, the number of each lymphocyte subset was decreased; however, only for CD3 and CD4 lymphocytes has a significant reduction been shown. On the contrary, tumour necrosis factor-alpha and IL-10 levels markedly increased and amounted to its maximum on day 30. Simultaneously, a significant reduction in plasma interferon-gamma and a profound decrease of the lymphocyte response to phytohaemagglutinin were shown. The changes were accompanied with marked elevation of plasma IL-4. Conclusions Our data indicate that the vaccination with live attenuated rubella vaccine results in moderate but sustained immune disturbance. The signs of immunosuppression, including defective lymphocyte response to mitogene and impaired cytokine production, may persist for at least 1 month after vaccination.
PMID: 14514470 [PubMed - in process]
Mediators Inflamm. 2003 Aug;12(4):203-7. Related Articles, Links
Cytokine profile after rubella vaccine inoculation: evidence of the immunosuppressive effect of vaccination.
Pukhalsky AL, Shmarina GV, Bliacher MS, Fedorova IM, Toptygina AP Fisenko JJ, Alioshkin VA.
Research Centre for Medical Genetics, 1 Moskvorechie Street, Moscow 115478, Russia. firstname.lastname@example.org
BACKGROUND AND AIM: Immunization with live virus vaccines may cause an immunosuppression with lymphopaenia, impaired cytokine production and defective lymphocyte response to mitogenes. These abnormalities were described in subjects vaccinated against measles. This study was performed to analyse the host immune response related to immunosuppression in subjects vaccinated with live attenuated rubella vaccine.
METHODS: Eighteen schoolgirls, aged 11-13 years, were vaccinated with live attenuated rubella vaccine Rudivax. Before immunization, and 7 and 30 days after, peripheral blood was collected. Cellular fractions were subjected to flow cytometric analysis, and the lymphocyte response to phytohaemagglutinin was investigated. Plasma samples were analysed for cytokines (interleukin (IL)-4, IL-10, tumour necrosis factor-alpha, and interferon-gamma) by enzyme-linked immunosorbent assay techniques.
RESULTS: On day 7 after vaccination, the number of each lymphocyte subset was decreased; however, only for CD3 and CD4 lymphocytes has a significant reduction been shown. On the contrary, tumour necrosis factor-alpha and IL-10 levels markedly increased and amounted to its maximum on day 30.
Simultaneously, a significant reduction in plasma interferon-gamma and a profound decrease of the lymphocyte response to phytohaemagglutinin were shown. The changes were accompanied with marked elevation of plasma IL-4.
CONCLUSIONS: Our data indicate that the vaccination with live attenuated rubella vaccine results in moderate but sustained immune disturbance. The signs of immunosuppression, including defective lymphocyte response to mitogene and impaired cytokine production, may persist for at least 1 month after vaccination.
PMID: 14514470 [PubMed - indexed for MEDLINE]
1: J Infect Dis. 1985 Sep;152(3):606-12. Links Postpartum rubella immunization: association with development of prolonged arthritis, neurological sequelae, and chronic rubella viremia. Tingle AJ, Chantler JK, Pot KH, Paty DW, Ford DK.
Six women developed chronic long-term arthropathy after postpartum immunization against rubella. All individuals developed acute polyarticular arthritis within 12 days to three weeks postimmunization and have had continuing chronic or recurrent arthralgia or arthritis for two to seven years after vaccination. Acute neurological manifestations, consisting of carpal tunnel syndrome or multiple paresthesiae, developed postvaccination in three women. Two have developed continuing active or chronic recurrent episodes of blurred vision, paresthesiae, and painful limb syndromes together with recurrent joint symptoms. Chronic rubella viremia has been detected in peripheral blood mononuclear cell (MNC) populations in five of the six women up to six years after vaccination. In addition rubella virus was isolated from breast milk MNCs in one individual at nine months postvaccination and from peripheral blood MNCs in two of four breast-fed infants studied at 12-18 months of age. Immune responses to rubella virus studied at sequential intervals after vaccination correlated with development of rheumatologic and neurological manifestations.
PMID: 4031558 [PubMed - indexed for MEDLINE]