Development and durability of measles antigen-specific lymphoproliferative response after MMR vaccination

The correlates of long-term protection from measles infection are poorly understood. We followed the development of measles-specific antibody and lymphoproliferative (LP) responses in 60 children for 6 months after MMR vaccination. Prevaccine plaque reduction neutralization antibody (PRN Ab) values were low (mean+/-SEM 9.9+/-1. 1). Ninety-three percent (56/60) had excellent PRN values at 6 months (PRN 1816+/-207). Prevaccine LP activity was also low (stimulation index (SI)=1.4+/-0.1) but increased rapidly (SI 10. 7+/-4.5 at 2-3 weeks; p<0.05). However, only 61% (37/60) of the children had both significant cellular and antibody responses (SI>/=3 and PRN>/=120: Ab(hi)CMI(hi)). One child had a strong LP response (SI=6.7) despite little antibody production (PRN=19 at 6 months: Ab(lo)CMI(hi)). We also conducted a cross-sectional study in a separate group of 87 children 5-13 years after MMR vaccination. PRN values >/=120 were present in most children at 5-8 (n=28) and 9-13 years (n=59) after vaccination (PRN 550+/-120 and 360+/-60, respectively) but a significant minority had either undetected or 'subprotective' values (29 and 34%, respectively). LP responses (SI>/=3) were detectable in 19/28 (66%) and 36/59 (56%) of the children 5-8 and 9-13 years after vaccination (SI 11.4+/-2.4 and 7. 75+/-1.9, respectively). Almost two thirds (18/28) of the children in the cross-sectional study with low or absent antibody titers (PRN 41+/-6) had strong LP responses to measles antigens (SI 6.8+/-1.3). These data suggest that LP responses may be better sustained than antibody titers in some children. The susceptibility of Ab(lo)CMI(hi) children to infection and the value of the early LP response for predicting the durability of immunity remain to be determined.     

Measles vaccination in the presence of maternal antibodies primes for a balanced humoral and cellular response to revaccination

Early or low dose antigen exposure can prime the immune system for subsequent responses; the so-called "prime-boost" effect. In the context of a Sudanese measles vaccine trial, we assessed whether or not such early exposure could influence the response to revaccination. Children received either Connaught high titer vaccine (CN: n = 53; 10(4.7)pfu) or meningococcal A + C vaccine as a placebo (MEN: n = 58) at 5 months of age. At 9 months of age, all received standard titer Schwarz vaccine (SCH: 10(3.9)pfu). Neutralizing antibodies were measured before initial vaccination and at 9 months of age (plaque reduction neutralization assay (PRN)) and again at 5 years of age (syncytium inhibition assay (SIA)). Lymphoproliferative responses to measles virus (MV) antigens were evaluated at 5 years of age. Eleven of the 53 CN-SCH children (21%) had sub-protective neutralizing antibody titers prior to revaccination (log PRN 1.5 +/- 0.03 versus 2.9 +/- 0.07 in the remaining 42 children; P < 0.004). Maternal antibody titers at the time of initial vaccination in these 11 were high (PRN 2.44 +/- 0.12 versus 1.9 +/- 0.04; P < 0.0001). At 5 years of age, neutralizing antibodies were comparable in the 11 CN-SCH poor responders (log SIA 2.1 +/- 0.09), the remaining CN-SCH children (2.2 +/- 0.06) and the MEN-SCH group vaccinated only once at 9 months of age (2.25 +/- 0.06). In contrast, 7/11 of the CN-SCH poor responders (64%) had stimulation indices (SI) > 3 in response to MV antigens at 5 years of age (SI 3.1 +/- 0.6) compared with only 14% in the remaining children of the CN-SCH group (2.0 +/- 0.3; P = 0.05) and 8% in the MEN-SCH group (1.4 +/- 0.2; P < 0.0003). These data suggest that early measles vaccination in the presence of maternal antibodies can sometimes prime for a balanced humoral and cellular immune response to subsequent revaccination.     

Effect of Vitamin A supplementation on the immune response to measles vaccination

A randomized controlled trial was conducted in 395 infants aged 9-12 months to determine the effect of Vitamin A supplementation on concurrently administered measles vaccine. Antibody response was measured using the plaque reduction neutralization assay. No statistically significant differences were demonstrated between the immune response in Vitamin A supplemented and unsupplemented children. Unlike some recent studies, we were unable to demonstrate an immune enhancing effect of Vitamin A supplementation. On the contrary, among children who were given Vitamin A, a lower, but statistically non-significant, proportion had protective antibody levels 6 months after vaccination.     

Supplemental measles vaccine antibody response among HIV-infected and -uninfected children in Malawi after 1- and 2-dose primary measles vaccination schedules

BackgroundThe long-term antibody response to measles vaccine (MV) administered at age 6 months with or without subsequent doses is not well documented.MethodsMeasles serum antibody responses were evaluated after a supplemental dose of measles vaccine (sMV) administered at a median age of 20 months among Malawian children who had previously received 2 doses of measles vaccine (MV) at ages 6 and 9 months (HIV-infected and random sample of HIV-uninfected) or 1 dose at age 9 months (random sample of HIV-uninfected). We compared measles antibody seropositivity between groups by enzyme linked immunoassay and seroprotection by plaque reduction neutralization geometric mean concentrations.ResultsOf 1756 children enrolled, 887 (50.5%) received a sMV dose following MV at 9 months of age and had specimens available after sMV receipt, including 401 HIV-uninfected children who received one MV dose at 9 months, 464 HIV-uninfected and 22 HIV-infected children who received two doses of MV at ages 6 and 9 months. Among HIV-uninfected children, protective levels of antibody were found post sMV in 90–99% through ages 24–36 months and were not affected by MV schedule. Geometric mean concentration levels of measles antibody were significantly increased post-sMV among those HIV-uninfected children previously non-responsive to vaccination. Among HIV-infected children, the proportion seroprotected increased initially but by 9 months post-sMV was no higher than pre-sMV.ConclusionsOur findings support early 2-dose MV to provide measles immunity for young infants without risk of interference with antibody responses to subsequent MV doses administered as part of SIAs.     

Early loss of measles antibodies after MMR vaccine among HIV-infected adults receiving HAART

Objective

: The objective of the study was to evaluate the immune response to measles vaccine of HIV-infected adults in comparison to HIV non-infected adults.

Design

We conducted a cross-sectional study to identify adults lacking measles antibodies. 26 HIV-infected patients and 22 controls found to be measles seronegative in the cross-sectional study, received the MMR vaccine. We prospectively followed patients and measured measles antibodies, and cellular proliferative responses against measles antigens. We registered all adverse events at baseline, 3 and 12 months after vaccination.

Methods

We determined measles antibodies by ELISA and cellular proliferative response in PBMC's at baseline, and repeated measurements at 3 and 12 months after vaccination.

Results

The humoral immune response to the vaccine between HIV-infected adults and the HIV-uninfected group was not statistically different at 3 months (81% vs. 86% respectively). One year after vaccination, a higher proportion of HIV-infected adults had lost measles antibodies in contrast to controls. The cellular response was not statistically different between the groups at baseline, 3 and 12 months after immunization despite the waning of antibodies at 12 months. No severe adverse events were observed. Most patients were receiving HAART and had a mean CD4+ cell count of 496 cells/mL.

Conclusions

The initial humoral immune response to measles vaccine was not different between HIV-infected adults and HIV-uninfected adults. However, HIV-infected adults have a rapid decline of measles antibodies despite their high CD4+ cell count and sustained cellular proliferative response.     

Evaluation of an early two-dose measles vaccination schedule.

Vaccination at 6 months of age followed by routine revaccination is recommended when exposure of infants to measles is likely. Dade County, Florida, began this early two-dose schedule during a large epidemic in 1986-1987 (i.e., 22% of cases occurred in infants aged 6-11 months). This schedule was continued routinely in high-risk areas. The effect of an early two-dose schedule on measles prevention in the county was examined by comparing measles vaccination coverage and epidemiology before (1985-1987) and after (1988-1996) the schedule became routine. To assess serologic response, seroprevalence of measles antibody among children aged 4-6 years in 1995 was examined. To evaluate vaccine effectiveness, a case-control study was conducted among preschool-aged children. Among those aged 2 years, vaccination coverage with > or =1 dose increased from 75% to 94% in 1996. The number of annual cases declined, and endemic measles transmission reportedly ended after 1993. Seroprevalence of plaque reduction neutralization antibody (titer > 1:120) among those receiving vaccination according to an early two-dose schedule and a single dose at age > or =12 months was 94% (95% confidence interval: 89, 98) and 98% (95% confidence interval: 95, 100). In these groups, vaccine effectiveness was comparably high. Early two-dose measles vaccination is associated with improved coverage and a comparably high level of humoral immunity and clinical protection as a single dose at age > or =12 months. This strategy can be useful in areas at high risk for measles among infants.     

Loss of maternally acquired measles antibodies in well-nourished infants and response to measles vaccination, Peru.

Clinical, anthropometric, and serological evaluations were conducted at birth and at 3, 6, 9, and 10 months (post measles vaccination) in 34 well-nourished Peruvian infants. Seroconversion rate after measles vaccination was 94 percent. The rate of antibody loss was a direct function of birth titer; at age 9 months, all children had identical mean titers regardless of their titer at birth. Differences in maternally acquired measles antibodies at birth were important only during the first six months of life.     

Immunological impact of an additional early measles vaccine in Gambian children: responses to a boost at 3 years

Background

Measles vaccine in early infancy followed by a dose at 9 months of age protects against measles and enhances child survival through non-specific effects. Little is known of immune responses in the short or long term after booster doses.

Methods

Infants were randomized to receive measles vaccine at 9 months of age (group 1) or 4 and 9 months of age (group 2). Both groups received a boost at 36 months of age. T-cell effector and memory responses using IFN-γ ELIspot and cytokine assays and antibody titres using a haemagglutination-inhibition assay were compared at various times.

Results

Vaccination at 4 months of age elicited antibody and CD4 T-cell mediated immune responses .Two weeks after vaccination at 9 months of age group 2 had much higher antibody titres than group1 infants; cell-mediated effector responses were similar. At 36 months of age group 2 antibody titres exceeded protective levels but were 4-fold lower than group 1; effector and cytokine responses were similar. Re-vaccination resulted in similar rapid and high antibody titres in both groups (median 512); cellular immunity changed little. At 48 months of age group 2 antibody concentrations remained well above protective levels though 2-fold lower than group 1; T-cell memory was readily detectable and similar in both groups.

Conclusions

An additional early measles vaccine given to children at 4 months of age induced a predominant CD4 T-cell response at 9 months and rapid development of high antibody concentrations after booster doses. However, antibody decayed faster in these children than in the group given primary vaccination at 9 months of age. Cellular responses after 9 months were generally insignificantly different.     

Antibodies to measles,mumps, and rubella virus in Thai children after two-dose vaccination at 9 months and 2.5 years: A longitudinal study

IntroductionThailand changed the schedule of childhood measles–mumps–rubella (MMR) vaccination in 2014, moving the second dose from the age of 6 years to 2.5 years. There are currently no data on antibody responses to the MMR vaccine since this recommendation.Material and methodsWe investigated antibody responses in a cohort of children who received two doses of MMR vaccine at the ages of 9 months and 2.5 years that was originally established to evaluate antibody levels to Bordetella pertussis antigens (ClinicalTrials.gov no. NCT02408926). Infants were born to mothers who previously received tetanus–diphtheria–acellular pertussis vaccine at 27–36 weeks of gestation. Anti-measles, -mumps, and -rubella virus IgG levels were measured at birth (cord blood) and the ages of 2 and 7 months (before the first MMR vaccination); 18 and 24 months (9 and 15 months, respectively, after the first dose); and 36 months (6 months after the second dose) using commercially available enzyme-linked immunosorbent assay kits.ResultsAt 7 months of age, 96.2%, 99.6%, and 98.8% of infants had no protection against measles, mumps, and rubella, respectively. Levels of antibody against all three antigens increased significantly after the first but not the second dose. At 6 months after two-dose vaccination, 97.4%, 84.8%, and 78.7% of children remained seroprotected against measles, mumps, and rubella, respectively.ConclusionsMaternally derived antibodies to measles, mumps, and rubella virus disappeared by the age of 7 months in Thai children. Two-dose MMR vaccination at 9 months and 2.5 years of age induced robust immune responses against these viruses.     

Immune modulation after measles vaccination of 6-9 months old Bangladeshi infants

Measles still causes high mortality in children younger than 1 year of age. Administration of high titre measles vaccines before 7 months of age led to increased overall mortality, raising questions as to the immunological effects of measles vaccine in young infants. We investigated the immune response to standard titre vaccines given to children in Bangladesh in a single dose at age 9 months, or two doses at 6 and 9 months. Of the children vaccinated at age 9 months, 95% serocoverted, compared with 70% at age 6 months. Delayed-type-hypersensitivity reactions to candida antigen were significantly reduced in both vaccine groups at 6 weeks post-vaccination, but responses to other recall antigens studied were not significantly different from controls. In both vaccine groups, peripheral blood lymphocytes isolated at 6 and 24 weeks after vaccination showed significantly higher expression of activation markers upon in vitro stimulation, and a sustained increase in IL-2 production. These findings suggest prolonged immune activation after measles vaccination at the same time as some reduction in delayed hypersensitivity responses. Further study of the clinical effects of these changes is warranted.     

Measles immunity and response to revaccination among secondary school children in Cumbria.

The prevalence of antibody to measles virus in 759 children aged 11-18 years attending a secondary school in Cumbria was measured using a salivary IgG antibody capture assay. Serum IgG antibody levels were measured using a plaque reduction neutralization assay in subjects whose saliva was antibody negative. Vaccination histories were obtained from the child health computer and general practice record. A total of 662 pupils (87% of those tested) had detectable measles-specific IgG in saliva. Of the remaining 97, 82 provided blood samples and 29 had serum neutralizing antibody levels above 200 mIU/ml. Afer adjusting for non-participation rates, the proportion considered non-immune (no IgG in saliva and < or = 200 mIU/ml in serum) was 9% overall, ranging from 6% in vaccinated children to 20% in unvaccinated children. Measles-mumps-rubella vaccine was given to 50 children of whom 38 provided post-vaccination serum and 32 saliva samples. Thirty (79%) had a fourfold or greater rise in serum neutralizing antibody and 28 (88%) developed IgG antibody in saliva. Half of the children considered non-immune by antibody testing would have been overlooked in a selective vaccination programme targeted at those without a history of prior vaccination. A programme targeted at all school children should substantially reduce the proportion non-immune since a primary or booster response was achieved in three quarters of previously vaccinated children with low antibody levels and in all unvaccinated children. While it is feasible to screen a school-sized population for immunity to measles relatively quickly using a salivary IgG assay, a simple inexpensive field assay would need to be developed before salivary screening and selective vaccination could substitute for universal vaccination of populations at risk of measles outbreaks. The salivary IgG assay provided a sensitive measure of a booster response to vaccination.     

Diminishing Immune Responses against Variants of Concern in Dialysis Patients 4 Months after SARS-CoV-2 mRNA Vaccination

Patients undergoing chronic hemodialysis were among the first to receive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations because of their increased risk for severe coronavirus disease and high case-fatality rates. By using a previously reported cohort from Germany of at-risk hemodialysis patients and healthy donors, where antibody responses were examined 3 weeks after the second vaccination, we assessed systemic cellular and humoral immune responses in serum and saliva 4 months after vaccination with the Pfizer-BioNTech BNT162b2 vaccine using an interferon-γ release assay and multiplex-based IgG measurements. We further compared neutralization capacity of vaccination-induced IgG against 4 SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Delta) by angiotensin-converting enzyme 2 receptor-binding domain competition assay. Sixteen weeks after second vaccination, compared with 3 weeks after, cellular and humoral responses against the original SARS-CoV-2 isolate and variants of concern were substantially reduced. Some dialysis patients even had no detectable B- or T-cell responses.     

Prevalence of antibodies to measles and rubella in Sana'a, Yemen

Prevalence of antibodies to measles and rubella was tested in sera collected from 1368 subjects in urban and rural Sana'a. Overall, 11.7% had no antibodies to measles and 14.6% had no antibodies to rubella, despite the fact that measles but not rubella vaccine is included in the vaccination program in Yemen. Of 89 children <5 years of age 49 (55.1%) had no detectable antibodies to measles, demonstrating that supplementary measles immunization campaigns are required to prevent virus circulation. Assessment of measles immune status among infants in the first year of life is required to determine the optimum age for measles vaccination. Rubella vaccination should be considered with care in Yemen.     

Changes of the immunological patterns against measles, mumps and rubella. A vaccination programme studied 3 to 7 years after the introduction of a two-dose schedule

A two-dose vaccination programme using a combined measles, mumps and rubella vaccine (MMR) and administration at the ages of 18 months and 12 years was introduced in 1982. The 12-year-old schoolchildren were tested yearly from 1985 to 1989 on serum samples obtained prior to and after vaccination. Each year between 420 and 756 children were tested. The method used for antibody testing was the haemolysis-in-gel (HIG) assay. For measles also the enzyme-linked immunosorbent assay (ELISA) and the neutralization titre (NT) were applied. Only minor variations of the prevaccination immunity to measles were seen during the period 3-7 years after introduction of the programme. The age groups studied had partly been vaccinated against measles earlier. Between 12 and 16% lacked prevaccination immunity. In contrast the immunity to mumps and rubella of the 12-year-old children decreased considerably during the study period. No general vaccination against these diseases had been performed. Thus the susceptibility to mumps increased from 14% in 1985 to 39% in 1989 and to rubella from 41 to 57%. The seroconversion rate of children seronegative for measles was high, i.e. 100% in 1985 and later varied between 96 and 97%. For mumps, the seroconversion rate was lower and varied between 72 and 88%. All sera converted to rubella. During the follow-up period there was a declining incidence of measles, mumps and rubella. The relationship between the vaccination and reduction of disease and natural immunity strongly suggests that the association is causal and that this vaccination policy reduced the transmission of infection.     

A study of maternally derived measles antibody in infants born to naturally infected and vaccinated women.

Maternal, cord and infant measles antibody levels were measured and compared in a group of 411 vaccinated mothers and 240 unvaccinated mothers, and their babies, between 1983 and 1991. Maternal and cord sera were tested by haemagglutination inhibition and/or enzyme-linked immunosorbent assay, and plaque reduction neutralization tests were also used to test infant sera. Geometric mean titres were significantly higher in the unvaccinated than in the vaccinated mothers (P < 0.001). Infants born to mothers with a history of measles had higher antibody levels at birth than infants of vaccinated mothers and, although the difference narrowed over time, continued to have higher levels up to 30 weeks of age. Between 5 and 7 months of age significantly more of the children of vaccinated mothers had plaque reduction neutralization antibody levels below that which would interfere with vaccination. As the boosting effect of circulating natural measles disappears, earlier measles vaccination may need to be considered, perhaps as part of a two-dose policy.     

合肥市55例小于1岁麻疹病例分析

目的　为了解和掌握我市小于 1岁年龄组麻疹发病原因 ,制定防制策略 ,加速我市控制麻疹的步伐 ,对 5 5例小于 1岁的麻疹病例进行分析。方法　通过全市麻疹监测和疫情报告两个系统上报的疑似麻疹病例 ,采集静脉血测麻疹IgM抗体 ,择其抗体阳性的麻疹确诊病例 5 5例进行详细调查 ,填写统一设计好的调查表 ,最后对调查表内容进行分析。结果　 5 5例中 ,小于 8月龄 2 6例 (47.3%) ,大于 8月龄 2 9例 (5 2 .7%) ;大于 8月龄 (麻疹免初月龄 )有麻疹疫苗 (MV)接种史的仅占 2 7.6 %,其中城市病例中 ,接种MV者占5 0 %,农村病例占 11.1%。结论　未到MV初免月龄的婴儿发病比例较多 ;农村MV接种及时率低是造成小于 1岁儿童麻疹发病多的主要原因。     

Rash after measles vaccination: laboratory analysis of cases reported in São Paulo,Brazil

OBJECTIVE: The clinical differential diagnosis of rash due to viral infections is often difficult, and misdiagnosis is not rare, especially after the introduction of measles and rubella vaccination. A study to determine the etiological diagnosis of exanthema was carried out in a group of children after measles vaccination. METHODS: Sera collected from children with rash who received measles vaccine were reported in 1999. They were analyzed for IgM antibodies against measles virus, rubella virus, human parvovirus B19 (HPV B19) using ELISA commercial techniques, and human herpes virus 6 (HHV 6) using immunofluorescence commercial technique. Viremia for each of those viruses was tested using a polimerase chain reaction (PCR). RESULTS: A total of 17 cases of children with exanthema after measles immunization were reported in 1999. The children, aged 9 to 12 months (median 10 months), had a blood sample taken for laboratory analysis. The time between vaccination and the first rash signs varied from 1 to 60 days. The serological results of those 17 children suspected of measles or rubella infection showed the following etiological diagnosis: 17.6% (3 in 17) HPV B19 infection; 76.5% (13 in 17) HHV 6 infection; 5.9% (1 in 17) rash due to measles vaccine. CONCLUSIONS: The study data indicate that infection due to HPV B19 or HHV 6 can be misdiagnosed as exanthema due to measles vaccination. Therefore, it is important to better characterize the etiology of rash in order to avoid attributing it incorrectly to measles vaccine.     

Mass measles vaccination in urban Burkina Faso, 1998

OBJECTIVE: To assess the impact of the National Immunization Days (NIDs) on measles vaccine coverage in Burkina Faso in 1998. METHODS: During the week after the campaign, in which measles vaccine was offered to children aged 9-59 months in six cities regardless of vaccination history, a cluster survey was conducted in Ouagadougou and Bobo Dioulasso, the country's two largest cities. Interviewers visited the parents of 1267 children aged up to 59 months and examined vaccination cards. We analysed the data using cluster sample methodology for the 1041 children who were aged 9-59 months. FINDINGS: A total of 604 (57%) children had received routine measles vaccination prior to the campaign, and 823 (79%) were vaccinated during the NIDs. Among those who had previously had a routine vaccination, 484 (81%) were revaccinated during the NIDs. Among those not previously vaccinated, 339 (78%) received one dose during the NIDs. After the campaign, 943 (91%) children had received at least one dose of measles vaccine. Better socioeconomic status was associated with a higher chance of having been vaccinated routinely, but it was not associated with NID coverage. CONCLUSION: The mass campaign enabled a substantial increase in measles vaccine coverage to be made because it reached a high proportion of children who were difficult to reach through routine methods.     

Measles susceptibility in children in Karachi, Pakistan

Measles, despite being vaccine preventable is still a major public health problem in many developing countries. We estimated the proportion of measles susceptible children in Karachi, the largest metropolitan city of Pakistan, one year after the nationwide measles supplementary immunization activity (SIA) of 2007-2008. Oral fluid specimens of 504 randomly selected children from Karachi, aged 12-59 months were collected to detect measles IgG antibodies. Measles antibodies were detected in only 55% children. The proportion of children whose families reported receiving a single or two doses of measles vaccine were 78% and 12% respectively. Only 3% of parents reported that their child received measles vaccine through the SIA. Among the reported single dose measles vaccine recipients, 58% had serologic immunity against measles while among the reported two dose measles vaccine recipients, 64% had evidence of measles immunity. Urgent strengthening of routine immunization services and high quality mass vaccination campaigns against measles are recommended to achieve measles elimination in Pakistan.     

早产儿对乙肝、脊灰、麻疹疫苗基础免疫应答及不良反应研究

目的探讨早产儿接种乙肝、脊灰、麻疹疫苗后的免疫效果及不良反应发生率。方法选择2010-2013年在咸宁市疾控中心接种门诊建证接种疫苗共105例早产儿为观察组,同时随机选择同期足月儿105例为对照组,比较两组新生儿接种乙肝、脊灰、麻疹疫苗后72h不良反应及异常反应发生率,应用酶联免疫法对二组儿童在完成三种疫苗全程免疫后1~2月进行免疫成功率检测。结果二组儿童接种三种疫苗72h不良反应:乙肝和麻疹疫苗主要发热和局部红肿,脊灰苗主要是发热和腹泻。乙肝、脊灰、麻疹疫苗免疫成功率分别为85.71%、89.52%和88.10%。结论早产儿与足月儿一样,对乙肝疫苗、脊灰疫苗和麻疹疫苗具有良好的免疫应答反应,接种乙肝疫苗、脊灰和麻疹疫苗的不良反应发生率与足月儿无明显差异。