May Result in Reduced Antibody Response
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
PMID: 11803074 [PubMed - indexed for MEDLINE]
Response to measles revaccination among Bolivian
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]
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
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
PMID: 7594723 [PubMed - indexed for MEDLINE]
Mixed results. - SM
Reach the Goal of Measles
Measles Infections in Immunized Persons
Poland, MD; Robert M. Jacobson, MD
Measles is the most transmissible disease known to man. During the
number of measles cases in the United States rose
dramatically. Surprisingly, 20% to 40% of these cases occurred in
had been appropriately immunized against measles. In
response, the United States adopted a two--dose universal measles
We critically examine the effect of vaccine
failure in measles occurring in immunized persons.
We performed a computerized bibliographic literature search (National
Medicine) for all English-language articles dealing with
measles outbreaks. We limited our search to reports of US
Canadian school-based outbreaks of measles, and we spoke
experts to get estimates of vaccine failure rates. In
devised a hypothetical model of a school where measles
rates could be varied, vaccine failure rates could be
and the percentage of measles cases occurring in immunized
could be determined.
We found 18 reports of measles outbreaks in very highly immunized school
71% to 99.8% of students were immunized against
measles. Despite these high rates of immunization, 30% to
(mean, 77%) of all measles cases in these outbreaks occurred
immunized students. In our hypothetical school
after more than 95% of schoolchildren are immunized against
the majority of measles cases occur in appropriately immunized
The apparent paradox is that as measles immunization rates rise to
in a population, measles becomes a disease of immunized
Because of the failure rate of the vaccine and the unique
transmissibility of the measles virus, the currently available
used in a single-dose strategy, is unlikely to
completely eliminate measles. The
success of a two-dose strategy to eliminate
measles remains to be determined.
Measles outbreak in 31 schools: risk factors for vaccine
failure and evaluation of a selective revaccination strategy.
Department of Preventive Medicine and Biostatistics, University of
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]
Investigation of a measles outbreak in a fully vaccinated
school population including serum studies before and after
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]
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]
[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]
[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]
Dis Child. 1978
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.
measles immunization campaign 203 children were
enrolled in an antibody response study. Of this group, follow-up
and sera samples were available from 125 children three weeks after
immunization and from 90 children ten months later. Seventy-six of the
had been previously vaccinated, ten had a history of measles and 39
vaccination or illness. Twenty-six of the children had prevaccination
hemagglutination inhibiting antibody titers of less than 5. Of this
had a primary immune response (IgM measles antibody) with geometric
(GMT) of 90 and 40 three weeks and ten months respectively after
In contrast, the other 14 children with initial titers of less than 5
secondary immune responses (only IgG measles antibody) with GMTs of 28
three weeks and ten months after vaccination. Since
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
secondary vaccine failures. Also noted in this study was a poor
correlation between historical data and actual measles antibody.
629246 [PubMed - indexed for MEDLINE]