[Epidemiological analysis of immunity against
vaccine-preventable diseases: rubella, measles, mumps and chickenpox]
[Article in German]
Buxbaum S, Doerr HW, Allwinn R.
Institut fur Medizinische Virologie der Universitatsklinik Frankfurt/Main,
BACKGROUND AND OBJECTIVE: Measles,
mumps, rubella and varicella
zoster virus (VZV)
infections are regarded as typical diseases of childhood: They are normally
clinically mild and result in lifelong immunity. Severe clinical
disease is known in immunocompromised patients; rubella virus infections
during pregnancy often result in congenital rubella syndrome. All these
diseases are preventable by vaccination which is recommended in Germany,
recently vaccination against VZV for teenager without immunity since July
2001. In the following study we screened for immunity against the four
viruses. PATIENTS AND METHODS: Serum samples were obtained at the Institute of
Medical Virology Frankfurt/Main from January 1999 until December 2000. We
tested for specific antibodies against measles (n = 915), against mumps (n =
857), against rubella (n = 1886) and against VZV (n = 2291). Seroprevalences
were determined in different age groups. RESULTS: Altogether the highest rate
of seronegatives is detected in younger children. VZV-seronegativity rates
decrease from 74 % to 32 % in younger children. Against rubella also in this
age group rate of seronegatives is found in 40 % and less than 10 % by
teenagers. From this age group also immunity against rubella is found
approximately in 80 % of seropositives. CONCLUSIONS: The following study shows
that high seronegative rates are detectable, and here specially against VZV-specific
antibodies. For seronegative teenagers, vaccination against VZV is now
recommended in Germany. Immunization rates of at least 95 % in childhood would
be effective in avoiding severe courses of disease and giving protection in
PMID: 11709730 [PubMed - indexed for MEDLINE]
Pathogenic aspects of measles virus infections.
Schneider-Schaulies S, ter Meulen V.
Institute of Virology and Immunobiology, University of Wurzburg, Germany.
Measles virus (MV) infections normally
cause an acute self limiting disease which is resumed by a virus-specific
immune response and leads to the establishment of a lifelong immunity.
Complications associated with acute measles can, on rare occasions, involve
the central nervous system (CNS). These are postinfectious measles
encephalitis which develops soon after infection, and, months to years after
the acute disease, measles inclusion body encephalitis (MIBE) and subacute
sclerosing panencephalitis (SSPE) which are based on a persistent MV infection
of brain cells. Before the advent of HIV, SSPE was the best studied slow viral
infection of the CNS, and particular restrictions of MV gene expression as
well as MV interactions with neural cells have revealed important insights
into the pathogenesis of persistent viral CNS infections. MV CNS complication
do, however, not large contribute to the high rate of mortality seen in
association with acute measles worldwide. The latter is due to a virus-induced
suppression of immune functions which favors the establishment of
opportunistic infections. Mechanisms underlying MV-mediated immunosuppression
are not well understood. Recent studies have indicated that MV-induced
disruption of immune functions may be multifactorial including the
interference with cytokine synthesis, the induction of soluble inhibitory
factors or apoptosis and negative signalling to T cells by the viral
glycoproteins expressed on the surface of infected cells, particularly
PMID: 10470275 [PubMed - indexed for MEDLINE]
[Measles. A viral illness with risk of permanent damage]
[Article in German]
Butenandt O, Weiss M.
Kinderklinik im Dr. von Haunerschen Kinderspital, Universitat Munchen.
Measles is a highly contagious exanthematous disease. After an incubation
period of almost two weeks, catarrhal prodromic, associated with initial
attacks of fever appear. Typical manifestations are Koplik's spots. The
exanthema appears together with the second rise in temperature.
The illness confers lifelong immunity.
In individual cases, an encephalitis resulting in permanent neurological
deficits must be expected. Every effort should be made to prevent this
condition from arising. To this end, immunization with a combination measles,
mumps, rubella (MMR) vaccine is recommended.
PMID: 10897970 [PubMed - indexed for MEDLINE]
Analysis of antibody response to the measles virus using
synthetic peptides of the fusion protein. Evidence of non-random pairing of T
and B cell epitopes.
Muller CP, Handtmann D, Brons NH, Weinmann M, Wiesmuller KH, Spahn G,
Wiesneth M, Schneider F, Jung G.
Laboratoire National de Sante, Luxembourg.
The measles virus induces a life-long
immune response associated with antibodies specific for the fusion
protein. To map the linear immunodominant recognition sites of the fusion (F)
protein of the measles virus, we have reacted a complete set of 108
overlapping pentadecapeptides with purified IgG obtained from donor sera with
elevated anti-measles titers. The antibodies recognized about 20% of the
peptides and generated a characteristic binding pattern, defining about 6 or 7
distinctive regions (31-75; 111-145; 151-165; 191-215; 271-320; 421-440;
481-530) which include the major hydrophobic segment (111-145) of the
intersubunit region and the C-terminal Cys-cluster region. The binding sites
were located in close proximity of the few experimentally defined T cell
epitopes. This pairing of T and B cell epitopes was corroborated by
computer-assisted T cell prediction. The significance of a non-random
association of T and B cell epitopes for processing and presentation is
discussed. It is speculated that in long-term immunity against measles (F
protein), B cells of the same sIg specificity play an important role both as
antigen presenting cells and as antibody producing cells. In contrast to human
sera from late convalescent donors, mouse and rabbit MV antisera with high
neutralizing titers as well as neutralizing MV-F specific monoclonal
antibodies did not react with the peptides.
PMID: 8109160 [PubMed - indexed for MEDLINE]
Persistent measles virus infection enhances major
histocompatibility complex class I expression and immunogenicity of murine
Gopas J, Itzhaky D, Segev Y, Salzberg S, Trink B, Isakov N, Rager-Zisman B.
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben
Gurion University of the Negev, Beer Sheva, Israel.
The effect of persistent measles virus infection on the expression of major
histocompatibility complex (MHC) class I antigens was studied. Mouse
neuroblastoma cells C1300, clone NS20Y, were persistently infected with the
Edmonston strain of measles virus. The persistently infected cell line,
NS20Y/MS, expressed augmented levels of both H-2Kk and H-2Dd MHC class I
glycoproteins. Activation of two interferon(IFN)-induced enzymes, known to be
part of the IFN system: (2'-5')oligoadenylate synthetase and
double-stranded-RNA-activated protein kinase, was detected.
Measles-virus-infected cells elicited cytotoxic T lymphocytes that recognized
and lysed virus-infected and uninfected neuroblastoma cells in an
H-2-restricted fashion. Furthermore, immunization of mice with persistently
infected cells conferred resistance to tumor growth after challenge with the
highly malignant NS20Y cells. The
rationale for using measles virus for immunotherapy is that most patients
develop lifelong immunity after recovery or vaccination
from this infection. Patients
developing cancer are likely to have memory cells. A secondary response
induced by measles-virus-infected cells may therefore induce an efficient
immune response against non-infected tumour cells.
PMID: 1347254 [PubMed - indexed for MEDLINE]
Duration of live measles vaccine-induced immunity.
Markowitz LE, Preblud SR, Fine PE, Orenstein WA.
Division of Immunization, Centers for Disease Control, Atlanta, GA 30333.
From the article:
Similar to immunity after natural measles infection, live measles
vaccine-induced immunity has been thought to be lifelong.
who subsequently develop measles have been considered primary vaccine
failures, defined as the failure of the initial vaccination to elicit an
appropriate immune response. Primary vaccine failures are believed to be
caused by (1) interference by maternal antibody when vaccination occurs at a
young age, (2) technical problems, such as improper vaccine storage or
administration, or (2) other unknown reasons. Transmission of measles
among older children in the United States, most of whom have been
appropriately vaccinated, has raised the question of whether waning
vaccine-induced immunity may also be responsible for some vaccine failures.
Current vaccination policy as well as mathematical models assume that
vaccine-induced immunity is life-long. If waning vaccine-induced
immunity does occur, changes in measles vaccination strategies might be
necessary. The purpose of this paper is to review information concerning
the duration and quality of measles vaccine-induced immunity.
Discussion: Several types of
studies have been applied to evaluate the duration and quality of measles
vaccine-induced immunity. The few reports of measles disease in persons
who had seroconverted after vaccination document that secondary vaccine
failure can occur. In addition two studies provide data on the potential
magnitude of the risk of secondary vaccine failure. However, most data
suggest that waning immunity is uncommon.
Many questions concerning the
duration of vaccine-induced immunity remain to be answered, including what
percentage of cases reported in previously vaccinated persons in the United
States is caused by primary or secondary vaccine failure, whether different
measles vaccine strains produce immunity which is more or less "durable",
whether reexposure to wild measles virus is important for maintenance of
vaccine-induced immunity and whether it is possible to identify individuals at
risk for waning immunity.
The consequences of waning measles
vaccine-induced immunity may be minor for individuals if secondary vaccine
failure is associated with mild disease. However, waning vaccine-induced
immunity could be of greater consequence to a population. Although
persons with subclinical reinfection have not been shown to transmit virus, it
is not known whether this is true for persons with secondary vaccine failure.
If these individuals are able to transmit disease to other susceptibles,
waning immunity, even in a small percentage of persons, may impede realization
of the goal of measles elimination. Revaccination may be successful in
decreasing the number of persons who become susceptible due to waning
immunity. However, it is not known whether revaccination of such persons
will result in sustained immunity.
Questions concerning duration of
vaccine-induced immunity and secondary vaccine failure were raised at the time
of vaccine licensure and discussed 10 to 15 years later when outbreaks
occurred in vaccinated children. Now, 26 years after licensure, many of
the same issues remain unresolved. Although waning immunity has been
documented to occur in a small proportion of vaccinees, the epidemiologic
significance of this is still unclear.
PMID: 2179836 [PubMed - indexed for MEDLINE]
Measles active and passive immunity in a worldwide
'The simplest of all virus disease is measles' said Kenneth Maxy 40 years ago
in a chapter on epidemiology. I hope that the data set out here provide the
reader with a sufficiently complete and clear picture of the factors that
determine measles epidemiology, that he or she will agree with Maxy's
prescient words. Measles is an antigenically complex virus, but few components
of the immune response to this virus are epidemiologically relevant.
The relevant components are durable
for a lifetime. They can be conveniently measured by serological tests,
and the results of these tests correlate well with measles immunity. The tests
show that measles is an extremely infectious disease, and that very high
antibody prevalence rates are needed for herd protection. The currently
available measles vaccine is capable of yielding adequate antibody prevalence
rates for herd immunity, but to achieve this, immunization procedural flaws
and faulty records must be kept to very low levels. The greatest obstacle to
worldwide control of measles is a failure of vaccination programs to produce
adequate herd immunity levels in less-developed countries. There, vaccine must
be given promptly after passive immunity wanes, because the level of
endemicity is so high. It is difficult to determine just what age is optimal,
because it varies from one country to another. Premature vaccination not only
fails to immunize, but also interferes with subsequent re-immunization.
Because we now know this, further direct tests of vaccine effectiveness in
very young children are ethically undesirable, and methods that use
determination of passively acquired antibody are to be preferred. The levels
of antibody that mothers have to pass to their children vary considerably.
These differences are important in comparisons of South Asian countries with
others, but not elsewhere. Differences in efficiency of transport of antibody
across the placenta also play a role, but usually a minor one. Most important
seems to be variation in antibody durability in the infant. Where families are
poor, the children acquire many infections at an early age, and passively
acquired antibody is swept out. These children who are least able to withstand
the effects of measles infection, are hit at the earliest age. To provide
protection for them, the vaccine must be given at a carefully determined age,
specific for each community. Only when this is done can we hope to reduce
measles worldwide to a sufficiently low level that it will be removed as a
threat to persons in the United States, or anywhere else.
PMID: 2685909 [PubMed - indexed for MEDLINE]
The molecular biology of the morbillivirus (measles) group.
Institute for Animal Disease Research, Pirbright Laboratory, Surrey, U.K.
The morbilliviruses are a closely related group of important human and animal
pathogens. The best known members of the group are measles virus in man and
canine distemper virus in dogs. The group also includes two other serious
animal diseases, rinderpest or cattle plague and peste des petits ruminants in
sheep and goats. The latter viruses are of great economic importance in
Africa, Asia and the Middle East. Persistence of these viruses in some form is
a possible mechanism whereby life-long
immunity is conferred on an infected individual. In addition to the
severe, often fatal, acute disease these viruses can, in rare cases, lead to a
fatal chronic disease of the CNS. Molecular biological studies will be
described which are beginning to elucidate their evolutionary relationships
and to provide a basis for understanding the role of individual virus genes in
PMID: 3332767 [PubMed - indexed for MEDLINE]
J Pediatr 1965; 66: 471-88
immunity to measles.
S, Giles JP, Friedman H, Stone S.
Studies on immunity to measles have been in progress since 1960.
Primary infection with measles virus was followed by evidence of detectable
antibody by the twelfth day; peak antibody titers were observed by the
twenty-first to the twenty-eighth day. Subsequently, in most instances
antibody persisted for at least four years at levels capable of completely
inhibiting measles infection. However, when antibody declined to minimal
or undetectable levels, exposure to measles virus was usually followed by an
asymptomatic infection and a booster response; under these circumstances
antibody was detectable by the seventh day and peak antibody levels were
observed by the twelfth day. These studies confirm the observation that
one attack of measles is followed by lifelong immunity. They also provide strong support for
the prediction that one inoculation of live measles-virus vaccine will confer