Assessment of immune status against measles,mumps, and rubella in young Kuwaitis: MMR vaccine efficacy

Seroprevalence studies on measles, mumps, and rubella immunoglobulin G (IgG) antibodies after the implementation of the measles-mumps-rubella (MMR) vaccine are lacking in Kuwait. This study is an age-stratified serological study to assess the herd immunity to measles, mumps, and rubella among the young Kuwaiti population to evaluate the effectiveness of the MMR vaccine. IgG antibody titers to mumps, measles, and rubella were determined with commercial immune-assay in serum samples of 1000 Kuwaitis aged 5 to 20 years. The highest level of seropositivity was to measles (94.6%), which was significantly higher in females than in males. The highest seronegativity was for mumps (29%). The percentage of the young Kuwaiti population who were serologically positive for all the components of the MMR vaccine was 47%, and 2% of the individuals were without any protective antibodies to measles, mumps, and rubella. Females aged 5 to 10 years were best protected to rubella; however, seronegativity in 8.2% of 11- to 20-year-old females makes them vulnerable to rubella virus infection and congenital complications during pregnancy. The study provided insight into the effect of the MMR vaccine on seroprevalence of antibodies against measles, mumps, and rubella in Kuwait, which will contribute to the global knowledge base of vaccine coverage and help to inform elimination strategies. The findings strengthen the need for a third dose of MMR vaccine and catch-up campaigns for the young Kuwaiti population to increase vaccination coverage and prevent waning immunity, especially among those who received only one dose of the vaccine during childhood.     

Measles seroprevalence in pregnant women in Soweto,South Africa: a nested cohort study

ObjectivesMeasles infection causes particularly severe disease in young children who, prior to vaccination, are dependent on maternal antibodies for protection against infection. Measles vaccination was introduced into the South African public immunization programme in 1983 and became widely available in 1992. The aim of this study was to determine measles-specific immunoglobulin G (IgG) levels in pregnant women living with and without HIV born before and after measles vaccine introduction in South Africa.MethodsMeasles IgG antibody level from blood obtained at the time of delivery was compared between women who were born before 1983 (n = 349) and since 1992 (n = 349). Serum samples were tested for measles IgG antibody using an enzyme-linked immunosorbent assay. Geometric mean titres (GMTs) and the proportion with seronegative (<200 mIU/mL) or seropositive titres (≥275 mIU/mL) were compared.ResultsWomen born since 1992 had lower GMTs [379.7 mIU/mL (95% CI 352.7–448.6)] and fewer were seropositive (55.9%, 195/349) than women born before 1983 [905.8 mIU/mL (95% CI 784.7–1045.5); 76.8%, 268/349], for both comparisons p < 0.001.ConclusionsWe found an association between measles vaccine implementation into the public immunization program in South Africa and peri-partum maternal measles immunity, where women born before vaccine introduction had higher measles IgG antibody titres and were more likely to be seropositive. These findings suggest a need to reconsider the infant measles immunization schedule in settings where women have derived immunity mainly from measles vaccine rather than wild-type virus exposure.     

Seroepidemiological study of measles after the 1992 nationwide MMR revaccination program in Taiwan

The incidence of measles declined rapidly in Taiwan after the introduction of the measles vaccine into the routine immunization schedule in 1978. However, an epidemic still occurred every 3–5 years until recently. A nationwide measles-mumps-rubella (MMR) revaccination program for school and preschool children has been in place since 1992 to control the indigenous transmission of measles. In order to understand the current immune status after this recent nationwide revaccination program, we determined the presence of measles IgG antibodies by enzyme-linked immunosorbent assay (ELISA) in 1,281 blood samples from healthy persons aged from 2 months to above 30 years collected between 1993 and 1995, and also in another batch of 90 sera samples from children aged 2 years collected before 1992. The results showed that 1) the measles antibody seropositive rate (36.4%) was lowest in children aged 5–7 months and rose to an unexpectedly high level of 85.8% at the age of 12–14 months, 2) the seropositive rate rose further to between 85.9% and 95.1% after 2 years of age and remained high in adults and pregnant women, and 3) the seropositive rate of the 2-year-old children collected before 1992 was 61.4%, which was significantly lower than the rate of the same age group collected after the nationwide MMR revaccination program. We conclude that the national revaccination program has promoted effectively measles immunity in Taiwan. This immunity explains the rarity of reported measles cases since the last epidemic in 1989. This revaccination program should continue and be extended to all preschool children and young adults so that indigenous measles can be eliminated by the year 2000. J Med Virol 51:32–35, 1997. © 1997 Wiley-Liss, Inc.     

Immune activation at effector and gene expression levels after measles vaccination in healthy individuals: a pilot study

Cellular immunity to measles vaccination is not fully understood at the effector response and gene expression levels. We enrolled 15 healthy individuals (15-25 years old) previously vaccinated with two doses of measles-mumps-rubella-II vaccine to characterize their cellular immunity. We detected a spectrum of lymphoproliferative response (median stimulation indices of 3.4), low precursor frequencies of interferon-gamma (median 0.11%) and interleukin-4 (median 0.05%) by Elispot, and cosecretion of Th1 and Th2 cytokines after measles virus stimulation. Further, global gene expression was examined in five subjects from this cohort after vaccination with an additional dose of measles vaccine (Attenuax, Merck) to identify the genes involved in measles immunity. Linear mixed effect models were used to identify genes significantly up or downregulated in vivo between baseline and Days 7 and 14 after measles vaccination. Measles vaccination induced upregulation of a set of 80 genes, which play a role in measles immunity, signal transduction, apoptosis, cell proliferation, and metabolic pathways. Among the 34 genes that were downregulated, only interferon-alpha is known to have a direct role in measles immunity. This study suggests that measles vaccination leads to activation of multiple cellular mechanisms that can override the immunosuppressant effects of the measles virus and induce immunity.     

High maternal HIV-1 viral load during pregnancy is associated with reduced placental transfer of measles IgG antibody

BACKGROUND: Studies among HIV-1-infected women have demonstrated reduced placental transfer of IgG antibodies against measles and other pathogens. As a result, infants born to women with HIV-1 infection may not acquire adequate passive immunity in utero and this could contribute to high infant morbidity and mortality in this vulnerable population. METHODS: To determine factors associated with decreased placental transfer of measles IgG, 55 HIV-1-infected pregnant women who were enrolled in a Nairobi perinatal HIV-1 transmission study were followed. Maternal CD4 count, HIV-1 viral load, and HIV-1-specific gp41 antibody concentrations were measured antenatally and at delivery. Measles IgG concentrations were assayed in maternal blood and infant cord blood obtained during delivery to calculate placental antibody transfer. RESULTS: Among 40 women (73%) with positive measles titers, 30 (75%) were found to have abnormally low levels of maternofetal IgG transfer (<95%). High maternal HIV-1 viral load at 32 weeks' gestation and at delivery was associated with reductions in placental transfer (P < 0.0001 and P = 0.0056, respectively) and infant measles IgG concentrations in cord blood (P < 0.0001 and P = 0.0073, respectively). High maternal HIV-1-specific gp41 antibody titer was also highly correlated with both decreased placental transfer (P = 0.0080) and decreased infant IgG (P < 0.0001). CONCLUSIONS: This is the first study to evaluate the relationship between maternal HIV-1 viremia, maternal HIV-1 antibody concentrations, and passive immunity among HIV-1-exposed infants. These data support the hypothesis that high HIV-1 viral load during the last trimester may impair maternofetal transfer of IgG and increases risk of measles and other serious infections among HIV-1-exposed infants.     

Mucosal IgA responses in healthy adult volunteers following intranasal spray delivery of a live attenuated measles vaccine

Measles remains an important cause of morbidity and mortality among children in the developing world. The goal of this study was to examine measles virus-specific mucosal immune responses in healthy immune (n = 24; plaque reduction neutralization [PRN] titers of ≥200 mIU/ml) and nonimmune (n = 24) young adult volunteers who received the monovalent Moraten measles vaccine via intranasal (spray delivery) or subcutaneous immunization. Serum, oral fluid, and nasal wash samples were examined for measles virus-specific and total IgG and IgA on day 0 (prior to vaccination) and on days 14, 28, and 90 after vaccination. Nonimmune subjects vaccinated subcutaneously developed high levels of measles virus PRN, IgG, and IgA antibodies in serum, oral fluid, and nasal washes. Total IgG and secretory IgA (sIgA) titers were increased in nasal washes, and total IgG was increased in oral fluid specimens. There was a strong correlation between PRN and measles virus-specific IgG titers measured in serum, oral fluid, and nasal washes, whereas a weak correlation was found between PRN and measles virus-specific IgA titers. Notably, intranasal measles vaccination resulted in increased production of measles virus-specific sIgA in oral fluid and nasal washes in nonimmune individuals, without evidence of a systemic immune response. In contrast, no significant vaccine-induced responses were observed in immune subjects, regardless of the route of immunization. These results demonstrate that (i) intranasal measles immunization can elicit a mucosal response independent of the induction of serum antibodies and (ii) both mucosal and systemic antibody responses following nasal or subcutaneous immunization are blunted by preexisting measles immunity.     

Long-Term Immunity to Measles after Allogeneic Hematopoietic Cell Transplantation: Factors Associated with Seroprotection before Revaccination

Measles can be a life-threatening infection in immunocompromised patients, especially after allogeneic hematopoietic cell transplantation (HCT) because of the corresponding loss of immunity. However, measles vaccines are live-attenuated, which is why measles vaccinations are recommended only in seronegative HCT recipients and in specific conditions. However, little data exist on the rates of seroprotection to measles with the current conditioning regimens and in long-term follow-up. The objectives of this study were to assess measles immunity before considering vaccination in a cohort of allogeneic HCT long-term survivors and to identify the factors associated with seropositivity/seroprotection. One hundred and twenty-six patients who underwent transplantation between 1 and 39 years earlier (median, 9 years) were assessed for measles immunity. Measles IgG titers were determined with an automated chemiluminescent immunoassay. Seropositivity/seroprotection was defined by an IgG titer >16.5 UA/mL. Patients underwent transplantation with a reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning in 46% of cases, mainly for acute leukemia (61%). Seventy-eight of the 126 patients (62%) were seropositive/seroprotected for measles. Among the seropositive patients, the patients who had been vaccinated before transplantation had a lower median IgG titer compared with those who had not (48 UA/mL versus 116 UA/mL). Myeloproliferative disorder, RIC or NMA conditioning, and absence of acute grade ≥II graft-versus-host disease were associated with seropositivity/seroprotection. With a 62% rate of seropositivity/seroprotection for measles at a median of 9 years after transplantation, our findings strongly support a systematic assessment of anti-measles antibody titers to avoid unnecessary vaccination in seroprotected patients.     

Use of a microquantity enzyme immunoassay in a large-scale study of measles, mumps, and rubella immunity in Italy

The seroprevalence of antibodies to measles, mumps, and rubella viruses (MMR) was determined in 1498 subjects in Catania, Italy, ranging in age from 1 month to 25 years. The study population was divided into seven age groups and sceeened by enzyme immunoassay using microquantities (10 l) of whole blood collected by fingerprick on filterpaper discs. The results showed that seroconversion for measles (87.6%) and mumps (73.2%) occurred between 6 and 10 years of age. The seroprevalence of antibodies to rubella virus increased slowly through the age groups, reaching the highest rate (93.3%) between 16 and 20 years of age. Passively transmitted maternal antibodies to mumps and rubella were absent in babies between 5 and 8 months of age, and a few cases positive for measles antibodies were found among babies 6 and 7 months of age. The enzyme immunoassay was demonstrated to be suitable for low-cost large-scale screening for MMR immunity. The rate of vaccine failure was also evaluated and found to be 9.5% for the measles virus, 12.9% for the mumps virus and 0.0% for the rubella virus.     

Kinetics of mouse antibody and lymphocyte responses during intranasal vaccination with a lipooligosaccharide-based conjugate vaccine

We investigated the kinetics of humoral immunity and its related cellular immune responses to intranasal (IN) immunization with a detoxified lipooligosaccharide (dLOS)-tetanus toxoid (TT) conjugate against nontypeable Haemophilus influenzae (NTHi) in mice. IN vaccination with dLOS-TT elicited high titers of LOS-specific IgA in nasal washes and IgG in sera during a course of 4 inoculations while high titers of TT-specific IgA and IgG were found in sera. A significant increase of LOS-specific IgA antibody forming cells (AFCs) was observed in nasopharyngeal-associated lymphoid tissue (NALT) and nasal passages. However, TT induced broad responses with higher numbers of IgA and IgG AFCs found in NALT and nasal passages, less but significant IgA AFCs in cervical lymphoid nodes (CLN), spleen, and lungs. Phenotypic analysis revealed a significant rise of total B220+ B-lymphocytes in NALT and CLN, particularly a rise in IgA+/IgM+ cells in the NALT after the immunization. The latter result was complied with a significant rise of IL-4 but not IFN-gamma positive CD4+ T-lymphocytes in NALT. Analysis of IgG antibody subclasses showed that an IgG1 response to both LOS and TT epitopes dominated in serum when compared to IgG2a. These kinetic antibody patterns and cellular responses may provide useful information regarding to effective mucosal vaccines against NTHi infections.     

Extinction of the human leukocyte antigen homozygosity effect after two doses of the measles-mumps-rubella vaccine

We have reported associations between human leukocyte antigen (HLA) homozygosity and low measles antibody levels after one dose of the measles, mumps, and rubella (MMR) vaccine. Here, we examined associations between HLA homozygosity and immune responses to MMR after two doses of vaccine. We examined associations between HLA homozygosity and measles antibody levels in a group of 178 children (cohort 1) as well as associations between homozygosity and antibody levels and lymphoproliferative responses to MMR in 346 children (cohort 2). In cohort 1, HLA homozygotes and heterozygotes had similar increases in measles antibody levels after a second dose of measles vaccine. In cohort 2, HLA homozygosity was not associated with measles immune measures after two doses of vaccine. Homozygosity at the DPB locus was associated with increased rubella antibody levels, and homozygosity at the class IA alleles was associated with lower mumps lymphoproliferative response. Homozygosity at increasing numbers of loci was also associated with lower mumps antibody levels and lymphoproliferative response. Therefore, two doses of the MMR vaccine appear to induce sufficient antibody levels and lymphoproliferative responses against measles and rubella, regardless of HLA homozygosity status. However, children who are HLA homozygous may be less protected against mumps compared with children who are heterozygous.     

广州市白云区2009年麻疹疫苗强化免疫效果评价

目的评估麻疹疫苗强化免疫的实施对控制麻疹发病的效果,探讨控制和消除麻疹的对策。方法综合分析麻疹疫苗强化免疫现场调查资料、评估法定传染病报告系统中麻疹发病率的变化。结果 2009年白云区麻疹疫苗强化免疫共接种目标人群362454人,报告接种率和调查接种率均大于95%;强化免疫后麻疹发病率锐减;零剂次免疫儿童主要分布在流动儿童。结论白云区2009年在强化活动后麻疹发病率显著降低。但如流动儿童较多地区常规免疫服务质量不能有效加强,还需要考虑1～2年后在该地区重点人群中开展后续强化免疫活动,以达到2012年消除麻疹的目标。     

Influence of HLA-DRB1 alleles on lymphoproliferative responses to a naturally processed and presented measles virus phosphoprotein in measles immunized individuals

Identification of stimulatory T-cell epitopes recognized by CD4+ T lymphocytes is important for vaccine development. Our previous studies using mass spectrometry identified a naturally processed HLA class II restricted DRB1*0301 T cell epitope in the measles virus phosphoprotein, MV-P1 (residues 179-197). Here we provide lymphocyte proliferation data from peripheral blood mononuclear cells (PBMC) obtained from 131 HLA-DRB1*0301-positive and HLA-DRB1*0301-negative (HLA discordant) individuals previously immunized against measles and report that a single amino acid substitution in the MV-P1 T cell epitope can reduce T cell proliferation and CD4+ T-cell recognition. Measles virus and measles peptide-specific lymphoproliferative responses and HLA-DRB1 allele associations reveal that the DRB1*0701 allele provided suggestive evidence of association with both measles virus (p = 0.03) and MV-P1 peptide (p = 0.06) lymphoproliferation. A marginally significant increase in the frequency of the *0301 allele (p = 0.10) was found among subjects who demonstrated low cellular responses to the measles virus. We found no associations between proliferation levels to the MV-P1 and MV-P2 peptides with *0301 alleles. We speculate that the glutamic acid at position 192 of the measles phosphoprotein is a critical immunogenicity factor and may influence the antigenicity of the naturally processed HLA class II MV-P1 epitope.     

Prevalence of IgG antibody against measles, mumps and rubella in bangladeshi children: a pilot study to evaluate the need for integrated vaccination strategy

The present study was carried out to determine the seroprevalence of IgG antibodies in Bangladeshi children against measles (irrespective of vaccination status), mumps and rubella (MMR) to assess strategic need of combined vaccination for these diseases. A total of 456 children of 1 month to 15 years, were studied. Serum IgG antibodies against MMR were measured by enzyme-linked immunosorbent assay (ELISA). By 3 months, protective IgG antibody level (>40 AU for measles and mumps and >15 IU/ml for rubella) for the diseases found to be between 50% and 80% among the studied children. Protective measles antibody (IgG) was not detected in all the children of 3-9 months and significant number of children between 9 months and 5 years were unprotected (87-65%; P < 0.001). Moreover, children of 3-15 months had no protective antibody level against mumps and significant number of children between 15 months and 5 years were unprotected (92-71%; P < 0.001). Between 5 and 15 years of age, significant number of children became protective (63-85%, P < 0.001). Although, a majority of children between 3 months and 5 years had shown to have no protective antibody against rubella (89-71%; P < 0.01-0.001) between >10 and 15 years 71% children had protective level of antibodies (P < 0.001). No significant difference was observed in antibody prevalence regarding socioeconomic classes, nutritional status and parental education. The data showed that: (i) a significant number of children remain unprotected against MMR in childhood and (ii) an extensive nationwide survey is required to suggest an integrated vaccination strategy in order to implement appropriate control measures of the three infectious diseases.     

Comparative assessment of determination of measles virus IgG antibodies in blood serum and dried whole blood

Enzyme immunoassay (Dade Behring Enzygnost diagnostic kit, Germany) was used to estimate the levels of measles virus IgG antibodies in 72 samples of blood serum and eluates of the whole blood dried on the Whatman 3M filter paper. The sensitivity of the dried blood test was 98.4%. The regression analysis showed a high correlation of the results (r2 = 0.89; regression coefficient 0.89). Measles virus IgG antibodies were ascertained to be retained in the dried blood at room temperature long (for at least 2 years). After 2-year storage at +4 degrees C, there was a reduction in the concentration of antibodies; however, they were still detectable in 62 (96.9%) out of 64 positive samples. The dried blood test is recommended for wide use to study immunity to measles virus.     

Seroprevalences of Specific IgG Antibodies to Measles,Mumps, and Rubella in Korean Infants

In this study, the seroprevalences of measles, mumps, and rubella antibodies in infants were determined to assess the immunization strategy and control measures for these infectious diseases. Serum samples from infants < 1 year of age and their mothers were collected to measure the concentrations of specific IgG antibodies to measles, mumps, and rubella by enzyme-linked immunosorbent assay. For selected infant serum samples, measles-specific neutralizing antibody levels were determined by using the plaque reduction neutralization test. The sera from 295 of infants and 80 of their mothers were analyzed. No infants had past measles, mumps, or rubella infections. Almost all infants < 2 months of age were positive for measles and rubella IgG antibodies. However, seroprevalence of measles and rubella antibodies decreased with age, and measles IgG and rubella IgG were barely detectable after 4 months of age. The seroprevalence of mumps antibodies was lower than that of measles and rubella antibodies in infants ≤ 4 months old, and mumps IgG was barely detectable after 2 months of age. The seropositivity of measles-specific neutralizing antibody was 63.6% in infants aged 2 months and undetectable in infants ≥ 6 months old. Because the seropositivity rates of measles, mumps, and rubella antibodies were low after the first few months of age in Korean infants, active immunization with vaccines is strongly recommended for infants aged 6–11 months when measles is epidemic. Timely administration of the first dose of measles-mumps-rubella vaccine at 12 months of age should be encouraged in non-epidemic situations.     

Prevalence of IgG-antibodies to mumps and measles virus in non-vaccinated children

The prevalence of mumps and measles IgG antibodies in a randomly selected population of children was determined by an enzyme-linked immunosorbent assay (ELISA) before routine measles-mumps-rubella (MMR) vaccination was introduced in Denmark. Testing of sera from about 2,520 Danish children between one and 17 years of age showed that mumps antibodies were acquired at an early age. The peak acquisition rate was between the ages of four and five; before the age of 15, 90% of children had antibodies to mumps. Immunity to measles occurred at an even earlier age; more than 50% of four-year-old and nearly all (98%) nine-year-old children had IgG antibodies to measles virus. The study showed that about 10% of the young adult Danish population was still susceptible to mumps infection whereas only about 1% of individuals at age 17 had not acquired immunity to measles virus.     

Measles immunity testing: comparison of two measles IgG ELISAs with plaque reduction neutralisation assay

Two commercial IgG ELISAs, one based on recombinant nucleocapsid antigen and one based on cell culture grown native virus antigens, were evaluated for measles immunity testing by comparison with plaque reduction neutralisation test (PRNT). Qualitative results of the two ELISAs showed 92% agreement with those of PRNT. The sensitivity of the two ELISAs was 89.6%. False negative ELISA results were obtained in 10% of sera, mainly sera containing low levels of neutralising antibody. The specificity of both ELISAs was 100%. Measles IgG ELISAs perform adequately for immunity testing, correctly identifying seronegative individuals for vaccination.     

Low immunity against vaccine preventable diseases in Turkish HIV cohort

Background/aimHIV infection increase the risk of serious disease resulting from common vaccine-preventable infections. Vaccinations are particularly important for HIV infected adults. We aimed to investigate the immunity rates against measles, mumps, rubella, hepatitis A, B, and tetanus in newly diagnosed HIV patients. Materials and methodsPatients who admitted to outpatient clinics of three centers with newly diagnosed HIV infection, between 1 January 2015 and 31 June 2017 were included. Measles, mumps, rubella, varicella zoster virus, hepatitis A, hepatitis B, and tetanus antibody levels were measured by commercial diagnostic kits. Demographical and laboratory data of the patients were recorded.ResultsFive hundred and twenty-three patients were enrolled in the study. Of the patients 87% were male (n = 455) and the mean age was 38 ± 13 years. Serology was available for measles 74.2% (388/523), mumps 73.8% (386/523), rubella 77.8% (407/523), hepatitis A 88.5% (463/523), hepatitis B 97.7% (511/523), tetanus 8.6% (45/523), and VZV 79.9% (418/523). Seropositivity was 82% for measles, 75.6% for mumps, 92.1% for rubella. Of the patients whom all three of the components of the MMR vaccine was tested, 37.7% (127/337) were susceptible at least one and needed the vaccine. Mean age was lower in patients who are nonimmune to measles and mumps (p = 0.008). Younger patients were also nonimmune for hepatitis A, while older patients were nonimmune for hepatitis B.ConclusionIn our study we found that rates of nonimmunity can increase up to one third of the patients even though there is a national vaccination program. Nonimmune individuals should be detected and vaccinated in line with recent guidelines and response should be monitored because of the possibility of impaired immunity and possible suboptimal response. National campaigns can be launched for adult immunization and physicians should be aware of the importance of adult immunization.