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Sandy Gottstein

President, Vaccination News, A Non-Profit Corporation

Waning vaccine-induced rubella immunity

Waning vaccine-induced rubella immunity

Epidemiol Infect 2000 Apr;124(2):263-71 Related Articles, Books, LinkOut

Secondary measles vaccine failures identified by measurement of IgG avidity: high occurrence among teenagers vaccinated at a young age.

Paunio M, Hedman K, Davidkin I, Valle M, Heinonen OP, Leinikki P, Salmi A, Peltola H.

Department of Public Health, University of Helsinki, Finland.

Failure to seroconvert (primary vaccine failure) is believed to be the principal reason (approx. > 95%) why some vaccinees remain susceptible to measles and is often attributed to the persistence of maternal antibodies in children vaccinated at a young age. Avidity testing is able to separate primary from secondary vaccine failures (waning and/or incomplete immunity), but has not been utilized in measles epidemiology. Low-avidity (LA) and high-avidity (HA) virus-specific IgG antibodies indicate primary and secondary failure, respectively. Measles vaccine failures (n = 142; mean age 10.1 years, range 2-22 years) from an outbreak in 1988-9 in Finland were tested for measles-virus IgG avidity using a protein denaturating EIA. Severity of measles was recorded in 89 failures and 169 non-vaccinees (mean age 16.2 years, range 2-22 years). The patients with HA antibodies (n = 28) tended to have clinically mild measles and rapid IgG response. Among failures vaccinated at < 12, 12-15 and > 15 months of age with single doses of Schwarz-strain vaccine in the 1970s, 50 (95% CI 1-99), 36 (CI 16-56) and 25% (CI 8-42) had HA antibodies, respectively. When a single measles, mumps and rubella (MMR) vaccine had been given after 1982 at 15 months of age, only 7% (CI 0-14) showed HA antibodies. Omitting re-vaccinees and those vaccinated at < 15 months, Schwarz-strain recipients had 3.6 (CI 1.1-11.5) higher occurrence of HA responses compared to MMR recipients. Apart from one municipality, where even re-vaccinees had high risk of primary infection, 89% (CI 69 to approximately 100) of the infected re-vaccinees had an HA response. Secondary measles-vaccine failures are more common than was more previously thought, particularly among individuals vaccinated in early life, long ago, and among re-vaccinees. Waning immunity even among individuals vaccinated after 15 months of age, without the boosting effect of natural infections should be considered a relevant possibility in future planning of vaccination against measles.

PMID: 10813152 [PubMed - indexed for MEDLINE]

Vaccine 2000 Jul 15;18(27):3106-12 Related Articles, Books, LinkOut
Click here to read 
Duration of rubella immunity induced by two-dose measles, mumps and rubella (MMR) vaccination. A 15-year follow-up in Finland.

Davidkin I, Peltola H, Leinikki P, Valle M.

National Public Health Institute, Helsinki, Finland.

A national two-dose vaccination program with a combined measles, mumps and rubella (MMR-II) vaccine was introduced in Finland, in 1982, immunizing children at the ages of 14-18 months and 6 years. Antibody levels were determined from serial samples from a group of originally 350 children during 15 years. The latest samples were taken 15.5 years after the first vaccination and 70% of the children could still be reached. The aim of this study was to determine the kinetics of rubella antibodies induced by the MMR-II vaccine in these individuals. Rubella antibodies were analyzed from three different cohorts: Group I seronegative children (n=166) vaccinated at 14-18 months and 6 years, Group II seronegative children (n=139) and Group III seropositive children (n=16) vaccinated at 6 and 11-13 years. Samples collected 0-9 years after vaccination were analyzed by hemolysis-in-gel (HIG) and later samples by enzyme immunoassay (EIA) techniques. The primary vaccination induced 100% seropositivity in vaccinees with a mean zone diameter of 10 (+/-1.3), 10.2 (+/-1.1) and 11.5 (+/-0.9) mm, in Groups I, II and III, respectively. The seropositivity rate was still high at 15 years, 99%, 100% and 100% with the geometric mean titer 23, 46 and 105 IU/ml, respectively. At 15 years, antibody levels <15 IU/ml which is the suggested protective level, were found in 31, 9 and 0% of children in Groups I, II and III, respectively. Because almost a third of the individuals in Group I now, at the age of 17 years, had low levels of rubella antibodies, it is possible that rubella infections may re-emerge during pregnancy. A careful surveillance including serological follow-up is therefore very important.

PMID: 10856790 [PubMed - indexed for MEDLINE]

Southeast Asian J Trop Med Public Health 2000 Mar;31(1):173-84 Related Articles, Books, LinkOut

Adult immunization--a neglected issue in Southeast Asia.

Isahak I; Steering Committee for Prevention and Control of Infectious Diseases in Asia.

Department of Medical Microbiology and Immunology, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur.

Adult immunization is a neglected and underpublicised issue in Southeast Asia. Vaccine-preventable diseases cause unnecessary morbidity and mortality among adults in the region, while inadequate immunization results in unnecessary costs, including those associated with hospitalization, treatment, and loss of income. Childhood vaccination coverage is high for the EPI diseases of diphtheria, tetanus and pertussis; however, unvaccinated, undervaccinated, and aging adults with waning immunity remain at risk from infection and may benefit from vaccination. Catch-up immunization is advisable for adults seronegative for hepatitis B virus, while immunization against the hepatitis A and varicella viruses may benefit those who remain susceptible. Among older adults, immunization against influenza and pneumococcal infections is likely to be beneficial in reducing morbidity and mortality. Certain vaccinations are also recommended for specific groups, such as rubella for women of child-bearing age, typhoid for those travelling to high-endemicity areas, and several vaccines for high-risk occupational groups such as health care workers. This paper presents an overview of a number of vaccine-preventable diseases which occur in adults, and highlights the importance of immunization to protect those at risk of infection.

Publication Types:
  • Review
  • Review, Tutorial

PMID: 11023089 [PubMed - indexed for MEDLINE]

"Rubella Vaccine" in "Vaccines" - by Stanley A. Plotkin, M.D.

"It thus appears that rubella immunity wanes after vaccination, but most vaccinees remain seropositive."

Epidemiol Infect 1999 Oct;123(2):263-70 Related Articles, Books, LinkOut

Prevalence of antibodies against rubella virus in The Netherlands 9 years after changing from selective to mass vaccination.

de Haas R, van den Hof S, Berbers GA, de Melker HE, Conyn-van Spaendonck MA.

Department of Infectious Diseases Epidemiology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.

A two-dose mass vaccination programme with a combined vaccine against measles, mumps and rubella (MMR) was adopted in the Netherlands in 1987, replacing the selective schoolgirl vaccination strategy introduced in 1974. To obtain insight into the effect of mass vaccination and the population's immunity, the antibody levels against rubella were studied in the general Dutch population and in religious groups refusing vaccination. In the national sample, we observed a high prevalence (96.5%) for rubella antibodies in vaccinated cohorts as well as in the older unvaccinated cohorts. No indications of rapidly waning immunity after vaccination were found. There are indications of low virus circulation in the last few years. The very high seroprevalence in women at childbearing age is consistent with the few reported cases of congenital rubella syndrome (CRS) at present. However, individuals in the age group of 1-9 years who are not vaccinated for religious or other reasons have a considerably lower seroprevalence and thus there is a potential risk of a CRS outbreak in the future.

PMID: 10579446 [PubMed - indexed for MEDLINE]

A contrary view. - SM

Vaccine 1999 Apr 9;17(15-16):2051-8 Related Articles, Books, LinkOut

Expression of interleukin-2 receptor alpha and CD45RO antigen on T lymphocytes cultured with rubella virus antigen, compared with humoral immunity in rubella vaccinees.

Toyoda M, Ihara T, Nakano T, Ito M, Kamiya H.

Department of Pediatrics, National Mie Hospital, Tsu, Japan.

We studied the expression of interleukin-2 receptor alpha (CD25)+ CD45RO+ CD4+ T lymphocytes (T-cell activation) in response to the rubella virus (RV) antigen (Matsuura strain, Biken, Osaka, Japan) using three-color-staining flow cytometry. The subjects were 48 healthy children (3-14 years old, 31 boys and 17 girls), who had received either monovalent vaccine (n = 5; mean age, 13.2 years) or measles-mumps-rubella (MMR) vaccine (n = 21; mean age, 10.5 years), had been naturally infected (n = 5; mean age, 11.4 years), or had been neither vaccinated nor naturally infected (n = 17; mean age, 10.0 years) and 62 healthy adolescents and adults (15-37 years old; 19 males and 43 females), who had received monovalent vaccine (n = 26, mean age, 27.4 years), had been naturally infected (n = 8; mean age, 24.0 years), or had been neither vaccinated nor naturally infected (n = 8; mean age, 16.5 years). Ninety-four of 110 subjects had HI titers > or = 1:16. T-cell activation in these subjects was significantly higher than that in 6 seronegative (HI titers < 1:8) subjects (p < 0.05). T-cell activation did not differ significantly with the history of exposure to RV. HI antibody titers > or = 1:16 and T-cell activation persisted in vaccinated subjects for > or = 20 years and was similar to those in naturally infected subjects. Our results suggest that cell-mediated immunity and humoral immunity persist for at least 20 years after vaccination.

PMID: 10217606 [PubMed - indexed for MEDLINE]

And another. - SM

Ann Med 1998 Apr;30(2):131-3 Related Articles, Books, LinkOut

Total elimination of measles in Finland.

Heinonen OP, Paunio M, Peltola H.

On average, 15,000 cases of measles occurred annually in Finland before the initiation of a vaccination programme in 1975. Because of insufficient activity, the vaccination coverage failed to reach the required level of over 90%, and cases continued to occur. The policy was revolutionized in 1982 by launching a project in which the Schwarz strain was substituted by an attenuated Enders-Edmonston strain given as a component of a trivalent live-virus measles-mumps-rubella vaccine (MMRII). This vaccine is given twice, at the ages of 14-18 months and 6 years. The impact of the vaccinations has been monitored in several prospective studies. In addition to a very favourable safety profile, good immunogenicity and excellent clinical effectiveness have also been demonstrated. Since 1996 not a single case of measles has been found in Finland, although cases have been searched actively and serological confirmation has been required. Total interruption of virus circulation has brought a new problem: the possibility of vaccinees to acquire natural boosters is so rare that waning immunity has become a reality. As there is a continuous risk of measles originating from a foreign source, the only tool against an outbreak is to maintain a high vaccination coverage and to continue the two-dose schedule as a minimum policy.

Publication Types:
  • Editorial

PMID: 9667790 [PubMed - indexed for MEDLINE]

Not specific to, but relevant re: rubella. - SM

Pediatr Infect Dis J 1996 Aug;15(8):687-92 Related Articles, Books, LinkOut
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Antibody persistence after primary measles-mumps-rubella vaccine and response to a second dose given at four to six vs. eleven to thirteen years.

Johnson CE, Kumar ML, Whitwell JK, Staehle BO, Rome LP, Dinakar C, Hurni W, Nalin DR.

Department of Pediatrics, Case Western Reserve University at MetroHealth Medical Center, Cleveland OH 44109-1998, USA.

BACKGROUND: Since 1989 the American Academy of Pediatrics and the ACIP have recommended a second dose of measles-mumps-rubella vaccine (M-M-R-II) at either school entry or age 11 to 13 years. Unfortunately few studies are available to compare responses to vaccine at the two ages. We performed a prospective trial to determine the persistence of antibody to measles, mumps and rubella vaccination in two age groups and the response to a second dose given at either 4 to 6 or 11 to 13 years. METHODS: Thirty-eight children 4 to 6 years old and 57 children 11 to 13 years old were given a second dose of M-M-R-II as they presented for yearly examinations. All had received the first dose at > or = 15 months of age. Measles and rubella antibody were measured by enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody (NT) assay, and mumps antibody was measured by an ELISA method only. An IgM-ELISA antibody assay for measles was used in selected children. Prevaccination and 3- to 4-week post-vaccination sera were obtained. Measles ELISA, measles-neutralizing antibody (NT) and rubella-neutralizing antibody (NT) assays were performed in all children. Seventy-nine of the 95 children had sufficient sera for repeat measles tests, as well as mumps and rubella ELISA determinations. RESULTS: Before the second dose ELISA seropositivity rates for measles and mumps were not significantly different between the two groups. Rubella ELISA seropositivity was 67% in 11- to 13-year-olds, compared with 90% in 4- to 6-year-olds (P < 0.01), suggestive of waning immunity. Rubella NT seropositivity was also lower in 11- to 13-year-olds than in 4- to 6-year-olds (63% vs. 100%, P < 0.01). After revaccination, 100% of the children become seropositive for all 3 antibodies. We performed measles IgM-ELISA testing on all 17 measles-seronegative children, as well as 15 seropositive children and 19 children who were 1 month postvaccination with the first M-M-R-II at 15 months. The purpose was to determine whether the seronegative children were primary or secondary failures. Five of the 17 children with undetectable pre-second dose antibody made IgM measles antibody after revaccination, suggesting that they were primary vaccine failures. CONCLUSIONS: Because all children became seropositive after revaccination, the age of administration can be based on the convenience of vaccine scheduling. However, in view of the apparent decline in rubella antibodies at 11 to 13 years, future studies of rubella vaccination should address the issue of whether earlier boosting leads to greater susceptibility at the time of reproductive age.

PMID: 8858673 [PubMed - indexed for MEDLINE]

: J Paediatr Child Health 1995 Feb;31(1):3-5 Related Articles, Books, LinkOut

Another vaccine, another treadmill?

Ferson MJ.

Public Health Unit, Eastern Sydney Area Health Service, Randwick, New South Wales, Australia.

OBJECTIVE: Attention is drawn to possible disadvantages arising from the introduction of universal varicella vaccination in infancy. METHODOLOGY: Comparisons are made between universal infant varicella vaccination and the current measles immunization programme, and a review of current literature on age-specific complications of varicella and cost-benefit analyses of varicella vaccination. RESULTS: Universal infant vaccination will cause a greater proportion of varicella cases to occur in adults, including pregnant women, who are at greater risk of serious complications compared to children. Although economic costs resulting from lost time from work will fall dramatically, health costs may rise. CONCLUSIONS: Universal infant vaccination should only be considered if measles is first controlled, and then only if more information on duration of protection becomes available and combined measles-mumps-rubella-varicella vaccines are approved.

PMID: 7748686 [PubMed - indexed for MEDLINE]

: Can J Public Health 1994 Jul-Aug;85(4):278-81 Related Articles, Books, LinkOut

Seroprevalence of measles- and rubella-specific antibodies among military recruits, Canada, 1991.

Duclos P, Tepper ML, Weber J, Marusyk RG.

Childhood Immunization Division, Bureau of Communicable Disease Epidemiology, Ottawa, ON.

A study of the seroprevalence of measles- and rubella-specific antibodies among military recruits in Canada in 1991 was undertaken to: 1) determine the proportion of military recruits who are measles and/or rubella seropositive when they enter the military; 2) detect general problems in the immune coverage in the young adult population; and 3) determine the proportion of measles seronegativity attributable to non-response, waning immunity or lack of exposure to either the disease or the vaccine. One initial blood sample was collected from all 399 recruits enrolled in basic training during the month of January 1991, prior to immunization with measles-mumps-rubella vaccine (MMR). Another sample was obtained from 354 of these recruits 3 to 5 weeks following this immunization. Only 18 (4.5%) recruits had negative measles-specific neutralization on the first sample. Only 12 (3.0%) recruits had negative measles-specific EIA on the first sample. All recruits had neutralization titres 40 or higher on the second sample. A total of 43 (10.8%) individuals had negative results for rubella EIA before immunization, 35 of which (81.4%) tested positive on the second sample.

PMID: 7987753 [PubMed - indexed for MEDLINE]

Pediatrie 1992;47(9):597-601 Related Articles, Books, LinkOut

[Reappearance of post-vaccination infection of measles, rubella and mumps. Should adolescents be revaccinated?]

[Article in French]

Malengreau M.

Measles-mumps-rubella immunization has had a dramatic impact on the incidence of these diseases and their complications. However, a partial coverage, as seen in Belgium and France, only slows the spread of the wild virus, thus increasing the age at infection and the risk of complications. This is to be added to the fact that there are 5% primary vaccine failure (no antibody production) and 5% secondary vaccine failure (loss of antibodies over time). When introducing first immunization at 15 months of age it is thus very important to increase quickly the immunization coverage by immunization of all non-immune children entering school and by re-immunization of all teenagers.

Publication Types:
  • Editorial
  • Review
  • Review, Tutorial

PMID: 1336841 [PubMed - indexed for MEDLINE]


Lijec Vjesn 1989 Apr-May;111(4-5):131-4 Related Articles, Books, LinkOut

[The development and duration of immunity in children vaccinated against measles with the Edmonston-Zagreb vaccine]

[Article in Serbo-Croatian (Roman)]

Borcic B, Smerdel S, Abu Eldan J, Kolic J, Ferdebar M, Kordic D, Mohacek N.

After routine measles-rubella-mumps (MRM) vaccine, seroconversion rate for measles heminhibiting (HI) antibodies in a group of 161 children was determined. Of the 154 children who had no HI antibodies in the first serum sample, 153 (99.3%) developed these antibodies in titres greater than or equal to 1:4 and 148 (96.1%) in titres greater than or equal to 1:8 at 6 weeks postvaccination. These results are in concord with the WHO standards. Another study was designed to evaluate persistence of HI antibodies to measles in a group of 123 children who were given MRM vaccine 1-6 years earlier. No significant decrease in HI antibody titers was recorded. It is concluded that immunity acquired through vaccination with the Edmonston-Zagreb measles virus strain in children aged 12 months to 3 years is satisfactory and that it does not decrease at least up to 6 years following vaccination.

PMID: 2770398 [PubMed - indexed for MEDLINE]

A contrary opinion.  However, later research indicates that HI antibodies reflect primary, not secondary vaccine failure (i.e., waning immunity).  - SM

: Rev Infect Dis 1985 Mar-Apr;7 Suppl 1:S157-63 Related Articles, Books, LinkOut

Challenge with rubella virus after loss of detectable vaccine-induced antibody.

Schiff GM, Young BC, Stefanovic' GM, Stamler EF, Knowlton DR, Grundy BJ, Dorsett PH.

Studies were conducted of experimental challenge with rubella virus in vaccinees whose possession of vaccine-induced antibody after vaccination had been documented and whose antibody level had become undetectable or very low over time. The challenge virus was the Howell strain, which had been shown to produce typical clinical and laboratory features of rubella in susceptible persons. The challenge of the vaccinees resulted in local viral replication in all but one; in viremia, a primary immunologic response, and a secondary antibody response in some; and usually in illness without a rash or in subclinical infection. The results emphasize the importance of continuing careful clinical and laboratory surveillance of vaccinees for determining the persistence of vaccine-induced immunity and of considering methods for identifying and revaccinating the minority of vaccinees who lose such immunity.

PMID: 4001723 [PubMed - indexed for MEDLINE]

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