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. rpebody@phls.org.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.
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. infdis@cesit1.unifi.it
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.
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.
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.
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%).
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.
[The results of multiyear observations on the duration of
the maintenance of immunity in those vaccinated and revaccinated against and
recovered from measles]
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.
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.
ALL INFORMATION, DATA, AND
MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION
PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS
OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR
LEGAL ADVICE. THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND
COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH
YOUR HEALTH CARE PROVIDER.
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