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Revaccination May Result in Reduced Antibody Response

Vaccine 2002 Jan 15;20(7-8):1134-40 Related Articles, Help
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Immunogenicity of second dose measles-mumps-rubella (MMR) vaccine and implications for serosurveillance.

Pebody RG, Gay NJ, Hesketh LM, Vyse A, Morgan-Capner P, Brown DW, Litton P, Miller E.

Sero-Epidemiology Unit, Immunisation Division, PHLS Communicable Disease Surveillance Centre, 61 Colindale Avenue, London, UK.

Measles and mumps, but not rubella, outbreaks have been reported amongst populations highly vaccinated with a single dose of measles-mumps-rubella (MMR) vaccine. Repeated experience has shown that a two-dose regime of measles vaccine is required to eliminate measles. This paper reports the effect of the first and second MMR doses on specific antibody levels in a variety of populations.2-4 years after receiving a first dose of MMR vaccine at age 12-18 months, it was found that a large proportion of pre-school children had measles (19.5%) and mumps (23.4%) IgG antibody below the putative level of protection. Only a small proportion (4.6%) had rubella antibody below the putative protective level. A total of 41% had negative or equivocal levels to one or more antigens. The proportion measles antibody negative (but not rubella or mumps) was significantly higher in children vaccinated at 12 months of age than at 13-17 months. There was no evidence for correlation of seropositivity to each antigen, other than that produced by a small excess of children (1%) negative to all three antigens. After a second dose of MMR, the proportion negative to one or more antigens dropped to <4%. Examination of national serosurveillance data, found that following an MR vaccine campaign in cohorts that previously received MMR, both measles and rubella antibody levels were initially boosted but declined to pre-vaccination levels within 3 years.Our study supports the policy of administering a second dose of MMR vaccine to all children. However, continued monitoring of long-term population protection will be required and this study suggests that in highly vaccinated populations, total measles (and rubella) IgG antibody levels may not be an accurate reflection of protection. Further studies including qualitative measures, such as avidity, in different populations are merited and may contribute to the understanding of MMR population protection.

PMID: 11803074 [PubMed - indexed for MEDLINE]

Trans R Soc Trop Med Hyg 1997 Nov-Dec;91(6):716-8 Related Articles, Help

Response to measles revaccination among Bolivian school-aged children.

Bartoloni A, Cutts FT, Guglielmetti P, Brown D, Bianchi Bandinelli ML, Hurtado H, Roselli M.

Clinica Malattie Infettive, Universita di Firenze, Italy.

The response to measles revaccination was evaluated in 1994 among 202 Bolivian school-aged children whose antibody levels were below 200 miu (milli-international units) by haemagglutination inhibition (HI) in a large-scale serosurvey conducted in Santa Cruz one year earlier. Of the 202 revaccinated children, 164 (82%) had seroconverted between the 1993 serosurvey and the pre-revaccination blood sample. A measles outbreak occurred in Santa Cruz 6 months before the revaccination. Among the seroconvertors, only 6% gave a history of measles, and 15% a history of contact with a case of measles. All 20 children with undetectable HI antibody pre-revaccination, and all 6 children with levels below 100 miu, seroconverted after revaccination. The geometric mean titres by HI at 4 weeks after revaccination were 2018 miu (95% confidence limits [95% CL] 1143, 3564) and 398 miu (95% CL 254, 625) in the 2 groups, respectively. Six of 9 children with pre-revaccination antibody titres of 100-199 miu also seroconverted. No child demonstrated a measles-specific immunoglobulin M response. Among the 29 children who seroconverted and were followed up at one year after revaccination, 15(52%) showed a fourfold or greater decline in antibody levels, which in 8 fell to levels below 200 miu. This study confirmed the observation that revaccination is successful in producing an antibody response in children with low or undetectable pre-revaccination titres, but it also confirmed that vaccine-induced immunity wanes rapidly.

PMID: 9509188 [PubMed - indexed for MEDLINE]

: J Infect Dis 1995 Dec;172(6):1591-5 Related Articles, Help

Cellular immunity in measles vaccine failure: demonstration of measles antigen-specific lymphoproliferative responses despite limited serum antibody production after revaccination.

Ward BJ, Boulianne N, Ratnam S, Guiot MC, Couillard M, De Serres G.

McGill Centre for the Study of Host Resistance, Montreal General Hospital, Quebec, Canada.

Measles antigen-specific immune responses were evaluated 1 and 6 months after revaccination in 60 previously vaccinated subjects (9.4 +/- 3.4 years of age) who had either undetectable or low plaque reduction neutralization (PRN) titers (< 200). PRN titers were increased in all subjects at 1 month (590 +/- 61; range, 129-2513) but fell again in 66% of subjects by 6 months (214 +/- 29; range, 30-794). At 6 months, 23 (38%) had subprotective (< 120) or borderline (< 200) PRN titers. Lymphoproliferative responses to measles virus antigens were low overall before revaccination (mean stimulation index [SI], 2.6 +/- 0.4; range, 0.5-13.5) but were readily detectable at 1 (SI, 145.8 +/- 2.6; range, 1.4-80) and 6 months after revaccination (SI, 9.4 +/- 1.8; range, 1.1-87). Before revaccination, 10 of the subjects (50%) with low positive PRN titers had SIs > or = 3. At 6 months after revaccination, 18 subjects (78%) with PRN titers < or = 200 had SIs > or = 3. These data suggest that cellular responses to measles virus may be better sustained than antibody titers after vaccination and revaccination in some subjects.

PMID: 7594723 [PubMed - indexed for MEDLINE]

Mixed results. - SM


Failure to Reach the Goal of Measles Elimination

Apparent Paradox of Measles Infections in Immunized Persons

Gregory A. Poland, MD; Robert M. Jacobson, MD

Arch Intern Med. 1994;154(16):1815-1820.


Measles is the most transmissible disease known to man. During the 1980s, the number of measles cases in the United States rose dramatically. Surprisingly, 20% to 40% of these cases occurred in persons who had been appropriately immunized against measles. In response, the United States adopted a two--dose universal measles immunization program. We critically examine the effect of vaccine failure in measles occurring in immunized persons.

We performed a computerized bibliographic literature search (National Library of Medicine) for all English-language articles dealing with measles outbreaks. We limited our search to reports of US and Canadian school-based outbreaks of measles, and we spoke with experts to get estimates of vaccine failure rates. In addition, we devised a hypothetical model of a school where measles immunization rates could be varied, vaccine failure rates could be calculated, and the percentage of measles cases occurring in immunized students could be determined.

We found 18 reports of measles outbreaks in very highly immunized school populations where 71% to 99.8% of students were immunized against measles. Despite these high rates of immunization, 30% to 100% (mean, 77%) of all measles cases in these outbreaks occurred in previously immunized students. In our hypothetical school model, after more than 95% of schoolchildren are immunized against measles, the majority of measles cases occur in appropriately immunized children.

The apparent paradox is that as measles immunization rates rise to high levels in a population, measles becomes a disease of immunized persons. Because of the failure rate of the vaccine and the unique transmissibility of the measles virus, the currently available measles vaccine, used in a single-dose strategy, is unlikely to completely eliminate measles. The longterm success of a two-dose strategy to eliminate measles remains to be determined.

(Arch Intern Med. 1994;154:1815-1820)


CMAJ 1994 Apr 1;150(7):1093-8 Related Articles, Help

Measles outbreak in 31 schools: risk factors for vaccine failure and evaluation of a selective revaccination strategy.

Yuan L.

Department of Preventive Medicine and Biostatistics, University of Toronto, Ont.

OBJECTIVE: To examine the risk factors for measles vaccine failure and to evaluate the effectiveness of a selective revaccination strategy during a measles outbreak. DESIGN: Matched case-control study. SETTING: Thirty-one schools in Mississauga, Ont. SUBJECTS: Eighty-seven previously vaccinated school-aged children with measles that met the Advisory Committee on Epidemiology's clinical case definition for measles. Two previously vaccinated control subjects were randomly selected for each case subject from the same homeroom class. INTERVENTIONS: All susceptible contacts were vaccinated, and contacts who had been vaccinated before Jan. 1, 1980, were revaccinated. When two or more cases occurred in a school all children vaccinated before 1980 were revaccinated. MAIN OUTCOME MEASURES: Risk of measles associated with age at vaccination, time since vaccination, vaccination before 1980 and revaccination. RESULTS: Subjects vaccinated before 12 months of age were at greater risk of measles than those vaccinated later (adjusted odds ratio [OR] 7.7, 95% confidence interval [CI] 1.6 to 38.3; p = 0.01). Those vaccinated between 12 and 14 months of age were at no greater risk than those vaccinated at 15 months or over. Subjects vaccinated before 1980 were at greater risk than those vaccinated after 1980 (adjusted OR 14.5, 95% CI 1.5 to 135.6). Time since vaccination was not a risk factor. Revaccination was effective in reducing the risk of measles in both subjects vaccinated before 1980 and those vaccinated after 1980 (adjusted OR reduced to 0.6 [95% CI 0.1 to 5.3] and 0.3 [95% CI 0.13 to 2.6] respectively). However, only 18 cases were estimated to have been prevented by this strategy. CONCLUSIONS: Adherence to routine measles vaccination for all eligible children is important in ensuring appropriate coverage with a single dose. The selective revaccination strategy's high labour intensiveness and low measles prevention rate during the outbreak bring into question the effectiveness of such a strategy.

PMID: 8137189 [PubMed - indexed for MEDLINE]

Pediatr Infect Dis J 1993 Apr;12(4):292-9 Related Articles, Help

Investigation of a measles outbreak in a fully vaccinated school population including serum studies before and after revaccination.

Matson DO, Byington C, Canfield M, Albrecht P, Feigin RD.

Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.

A measles outbreak in early 1989 among approximately 4200 students at a high school and two intermediate schools in suburban Houston, TX, was investigated to evaluate reasons for vaccine failure and to predict the efficacy of a booster dose of measles vaccine. Seventy-seven cases occurred (71 at the high school, 6 at intermediate schools; attack rate, 3.2 and 0.3%, respectively). Vaccination in the first year of life an 13 to 14 years since last vaccination were independent risk factors for being a case. Forty-three (18%) of 239 sera collected from students just before revaccination during the outbreak were negative by enzyme immunoassay; a neutralization assay confirmed these 43 lacked antibody predicting protection against measles infection. Of 43 enzyme immunoassay-negative students 24 gave another blood sample 9 to 10 months after revaccination. Revaccination appeared to reduce the portion of all students with neutralization titers predicting susceptibility to measles illness with rash from 7.9% to 3.0% and left the portion predicted to be susceptible to illness without rash unchanged (45%).

PMID: 8483623 [PubMed - indexed for MEDLINE]

J Adolesc Health 1991 May;12(3):273-8 Related Articles, Help

Serological response to measles revaccination in a highly immunized military dependent adolescent population.

Veit BC, Schydlower M, McIntyre S, Simmons D, Lampe RM, Fearnow RG, Stewart J.

Department of Clinical Investigation, William Beaumont Army Medical Center, El Paso, Texas 79920-5001.

In the spring of 1986, there was a measles outbreak in the city of El Paso, Texas, with 92 cases reported to the City-County Health Department. Of those 92 cases, 31 (32%) occurred within a public high school's student population of 2524. A mass measles vaccination program was undertaken at that high school in order to limit the outbreak. The student enrollment included a military dependent population of 368 students. Despite documented histories of prior measles immunizations in this military dependent subgroup, three individuals contracted the disease. Since this subgroup of students represented a highly immunized adolescent population, it was of interest to serologically determine their immune status prior to and following reimmunization with the expectation that such a study would provide information relating to the level of "protective" immunity. Prevaccination and postvaccination sera were obtained from 95 students. Results of measuring anti-measles antibody activity by ELISA indicate that 13 (14%) students responded to revaccination and experienced a fourfold or greater rise in IgG antibody levels. There were no detectable IgM responses. All of the students who responded to revaccination produced an anamnestic response (IgG boost only). Since most of these individuals had received first immunizations at 15 months of age or older, these findings suggest that secondary vaccine failure (waning immunity) was responsible for the putative "lowered" immunity in these individuals, instead of primary vaccine failure (maternal antibody suppression). These findings support current recommendations for measles booster revaccination of school-age children and adolescents.

PMID: 2054370 [PubMed - indexed for MEDLINE]

Zh Mikrobiol Epidemiol Immunobiol 1990 Aug;(8):66-70 Related Articles, Help

[The results of multiyear observations on the duration of the maintenance of immunity in those vaccinated and revaccinated against and recovered from measles]

[Article in Russian]

Sliusar' LI, Sokhin AA, Radomskaia FS, Degtiareva GV, Panasenko LI, Litvinova TP, Komarevskaia RV, Bol'shinskaia ZhI.

The results of 5-year observations on the duration of immunity to measles virus in persons vaccinated and revaccinated against measles, as well as in persons having had this infection, are presented. The intensity of immunity was determined in the same persons with the use of the passive hemagglutination test. The study revealed differences in the formation, intensity and duration of postvaccinal immunity. A significant decrease in the concentration of antibodies over the period of 5 years was established in 50.0-52.3% of vaccines. Revaccination with live measles vaccine is an effective measure for enhancing immunity to measles virus in persons with initial antibody titers less than 1:10-1:20, but revaccination made in a single injection is not sufficient for the stable maintenance of measles morbidity at the sporadic level. Postinfectious immunity is characterized by stability and has no tendency towards decrease. Persons having had measles have no need in additional measures irrespective of the time elapsed after the disease.

PMID: 2239007 [PubMed - indexed for MEDLINE]

Zh Mikrobiol Epidemiol Immunobiol 1979 Feb;(2):46-50 Related Articles, Help

[Effectiveness of revaccination against measles]

[Article in Russian]

Bolotovskii VM, Gelikman BG, Kibrik LI, Auzinia AV, Glinskaia EV.

The authors studied the efficacy of measles revaccination in children in whose serum no specific antihemagglutinins were revealed in titration with 1 GAE antigen (the first group) and having no specific antibodies in titration with 4 GAE antigen (the second group). Investigations demonstrated that children in whose blood serum no measles antibodies were revealed in the presence of 1 GAE antigen were subject of vaccination. Repeated vaccination used at present in persons who produced minimal antibody concentrations in response to vaccination is not recommended.

PMID: 419909 [PubMed - indexed for MEDLINE]

Am J Dis Child. 1978 Mar;132(3):287-90.

Measles revaccination. Persistence and degree of antibody titer by type of immune response.

Deseda-Tous J, Cherry JD, Spencer MJ, Welliver RC, Boyer KM, Dudley JP, Zahradnik JM, Krause PJ, Walbergh EW.


During a measles immunization campaign 203 children were enrolled in an antibody response study. Of this group, follow-up clinical data and sera samples were available from 125 children three weeks after immunization and from 90 children ten months later. Seventy-six of the children had been previously vaccinated, ten had a history of measles and 39 denied vaccination or illness. Twenty-six of the children had prevaccination hemagglutination inhibiting antibody titers of less than 5. Of this group 12 had a primary immune response (IgM measles antibody) with geometric mean titers (GMT) of 90 and 40 three weeks and ten months respectively after vaccination. In contrast, the other 14 children with initial titers of less than 5 had secondary immune responses (only IgG measles antibody) with GMTs of 28 and 9 three weeks and ten months after vaccination. Since the antibody responses in these children who had previously been stimulated by measles antigen were modest and transient, it is suggested that booster immunization may not be effective in preventing future secondary vaccine failures. Also noted in this study was a poor correlation between historical data and actual measles antibody.

PMID: 629246 [PubMed - indexed for MEDLINE]

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