Durability of humoral immune responses to rubella following MMR vaccination.

BACKGROUND: While administration of the measles-mumps-rubella (MMR-II®) vaccine has been effective at preventing rubella infection in the United States, the durability of humoral immunity to the rubella component of MMR vaccine has not been widely studied among older adolescents and adults. METHODS: In this longitudinal study, we sought to assess the durability of rubella virus (RV)-specific humoral immunity in a healthy population (n = 98) of adolescents and young adults at two timepoints: ~7 and ~17 years after two doses of MMR-II® vaccination. Levels of circulating antibodies specific to RV were measured by ELISA and an immune-colorimetric neutralization assay. RV-specific memory B cell responses were also measured by ELISpot. RESULTS: Rubella-specific IgG antibody titers, neutralizing antibody titers, and memory B cell responses declined with increasing time since vaccination; however, these decreases were relatively moderate. Memory B cell responses exhibited a greater decline in men compared to women. CONCLUSIONS: Collectively, rubella-specific humoral immunity declines following vaccination, although subjects' antibody titers remain well above the currently recognized threshold for protective immunity. Clinical correlates of protection based on neutralizing antibody titer and memory B cell ELISpot response should be defined.

Decreased humoral immunity to mumps in young adults immunized with MMR vaccine in childhood.

In the past decade, multiple mumps outbreaks have occurred in the United States, primarily in close-contact, high-density settings such as colleges, with a high attack rate among young adults, many of whom had the recommended 2 doses of mumps-measles-rubella (MMR) vaccine. Waning humoral immunity and the circulation of divergent wild-type mumps strains have been proposed as contributing factors to mumps resurgence. Blood samples from 71 healthy 18- to 23-year-old college students living in a non-outbreak area were assayed for antibodies and memory B cells (MBCs) to mumps, measles, and rubella. Seroprevalence rates of mumps, measles, and rubella determined by IgG enzyme-linked immunosorbent assay (ELISA) were 93, 93, and 100%, respectively. The index standard ratio indicated that the concentration of IgG was significantly lower for mumps than rubella. High IgG avidity to mumps Enders strain was detected in sera of 59/71 participants who had sufficient IgG levels. The frequency of circulating mumps-specific MBCs was 5 to 10 times lower than measles and rubella, and 10% of the participants had no detectable MBCs to mumps. Geometric mean neutralizing antibody titers (GMTs) by plaque reduction neutralization to the predominant circulating wild-type mumps strain (genotype G) were 6-fold lower than the GMTs against the Jeryl Lynn vaccine strain (genotype A). The majority of the participants (80%) received their second MMR vaccine ≥10 years prior to study participation. Additional efforts are needed to fully characterize B and T cell immune responses to mumps vaccine and to develop strategies to improve the quality and durability of vaccine-induced immunity.

Revaccination With Measles-Mumps-Rubella Vaccine and Infectious Disease Morbidity: A Danish Register-based Cohort Study.

Background: It has been hypothesized that revaccination with live vaccines is associated with reductions in off-target morbidity and mortality. We examined if revaccination with the live measles, mumps, and rubella vaccine (MMR) is associated with a lower rate of off-target infections. Methods: We performed a register-based nationwide cohort study that included 295559 children born in Denmark from April 2004 to December 2010. The cohort were followed from age 47 months (1 month before turning age 4 years, which is the recommended age of the second MMR [MMR-2]) until age 60 months. In Cox regression, we estimated adjusted incidence rate ratios (aIRRs) of antibiotic prescriptions and hospital admissions for any infection comparing MMR-2 as most recent vaccine with not having MMR-2 as the most recent vaccine. Results: There was no association between MMR-2 and antibiotic prescriptions (aIRR, 1.01; 95% confidence interval [CI], 0.99-1.02). The aIRR for the association between MMR-2 and admissions for infection of any duration was 0.93 (95% CI, 0.88-0.98). For admissions for infection lasting 0 to 1 day, the aIRR was 0.97 (95% CI, 0.90-1.03) compared with the aIRR of 0.84 (95% CI, 0.74-0.95) for admissions for infection lasting 2 days or longer (test for equality of aIRRs, P = .039). Conclusions: In this study, revaccination with MMR appeared safe in relation to off-target infections and was associated with a lower rate of severe off-target infections. More studies of the possible association between revaccination with live attenuated vaccines and off-target infections are needed.

Mässlingsvaccin kan ges vid 6 månaders ålder i särskilda fall - Vid risk för smitta kan off label-användning övervägas, enligt en litteraturgenomgång.

MMR vaccination in 6-9 month olds Vaccination against measles using the MMR vaccine is licensed from 9 months of age, but is used off-label from 6 months of age during or when travelling to areas with an ongoing measles outbreak. In this review of the published literature, studies on MMR vaccination in this age group are limited and small in size. Immunogenicity studies indicate that infants under 9 months respond with lower antibody titres but comparable T cell responses against measles. The safety profile of the vaccine does not appear to differ between infants vaccinated earlier or later. Vaccination from 6 months of age should be recommended if the risk of being infected with measles is considered greater than the risk of not attaining full vaccination protection.

Combination Measles-Mumps-Rubella-Varicella Vaccine in Healthy Children: A Systematic Review and Meta-analysis of Immunogenicity and Safety.

A combined measles-mumps-rubella-varicella (MMRV) vaccine is expected to facilitate universal immunization against these 4 diseases. This study was undertaken to synthesize current research findings of the immunogenicity and safety of MMRV in healthy children.We searched PubMed, Embase, BIOSIS Previews, Web of Science, Cochrane Library, and other databases through September 9, 2014. Eligible randomized controlled trials (RCTs) were selected and collected independently by 2 reviewers. Meta-analysis was conducted using Stata 12.0 and RevMan 5.3.Twenty-four RCTs were included in qualitative synthesis. Nineteen RCTs compared single MMRV dose with measles-mumps-rubella vaccine with or without varicella vaccine (MMR + V/MMR). Similar seroconversion rates of these 4 viruses were found between comparison groups. There were comparable geometric mean titers (GMTs) against mumps and varicella viruses between MMRV group and MMR + V/MMR group. MMRV group achieved enhanced immune response to measles component, with GMT ratio of 1.66 (95% confidence interval [CI] 1.48, 1.86; P < 0.001) for MMRV versus MMR and 1.62 (95% CI 1.51, 1.70; P < 0.001) for MMRV versus MMR + V. Meanwhile, immune response to rubella component in MMRV group was slightly reduced, GMT ratios were 0.81 (95% CI 0.78, 0.85; P < 0.001) and 0.79 (95% CI 0.76, 0.83; P < 0.001), respectively. Well tolerated safety profiles were demonstrated except higher incidence of fever (relative risks 1.12-1.60) and measles/rubella-like rash (relative risks 1.44-1.45) in MMRV groups.MMRV had comparable immunogenicity and overall safety profiles to MMR + V/MMR in healthy children based on current evidence.

Reactogenicity and immunogenicity of measles-rubella combined vaccine in school-entry-aged subjects with naturally acquired measles immunity.

BACKGROUND: The reintroduction of measles-rubella combined (MR) vaccination to Japan raised concerns about adverse events as well as immunogenicity related to booster immunization in subjects with naturally acquired immunity to measles or rubella. METHODS: The time course of reactogenicity and antibody responses in recipients with pre-existing immunity to measles through natural infection was observed. Eighteen children aged 80-104 months received MR booster vaccination; 16 of them had had previous rubella vaccination. RESULTS: There were virtually no clinical reactions related to booster vaccination, and a highly significant antibody response to rubella antigen, whereas the antibody rise to measles was statistically significant but poor. CONCLUSIONS: Vaccination of individuals already immune is not harmful. Booster immunization to rubella for Japanese children is vitally important.

Protective potential of MMR vaccine against complete Freund's adjuvant-induced inflammation in rats.

The aim of the present study was to investigate the effect of MMR vaccine on inflammation which was induced by complete Freund's adjuvant (CFA) in male Sprague-Dawley rats. Rats were randomly divided into the control, CFA, MMR and CFA + MMR groups. Inflammatory symptoms such as paw oedema was measured in CFA-injected rats' paw. Body weight changes and alterations in some haematological parameters and oxidative stress markers following CFA injection were checked. In CFA-inflammed rats, there was a significant increase in rat paw thickness and decrease in body weight increment. MMR exhibited a significant anti-inflammatory effect as manifested by reduction in paw thickness and normal gain in body weight when administered 1 week prior to induction of inflammation. The altered haematological parameters (TLC) and oxidative stress markers (MDA, GSH, SOD) in the inflammed rats were significantly brought back to near normal by MMR treatment. In conclusion, MMR vaccine showed a reduction in rat paw thickness and it could significantly normalize the haematological and biochemical abnormalities in CFA-induced inflammatory pain model in rats. Our data suggested that MMR could be a potential protective agent against certain types of inflammatory pain. Further histopathological and radiological studies are required to confirm the possibility of developing novel therapeutic vaccines against some forms of arthritis.

Reappraisal of MMR vaccines currently used in Korea.

BACKGROUND: Although MMR vaccine is widely used in Korea, there are limited studies on the currently used vaccines. We evaluated the immunogenicity and safety of MMR vaccines in Korean children. METHODS: For first and second dose immunization, children aged 12-23 months and 4-6 years were enrolled. All subjects received a single dose of either Priorix™ (Glaxo Smithkline Biologicals, Rixensart, Belgium) or MMRII® (Merck & Co., Inc., West Point, PA, USA). Pre- and postvaccine sera were collected from all participants. Antibody levels were determined by ELISA (Enzygnost®; Dade Behring, Schwalbach, Germany). Safety monitoring included local adverse events for 5 days and systemic adverse events for 42 days following vaccination. RESULTS: One hundred twenty-one subjects were enrolled in the 12-23 months age group and 39 in the 4-6 years age group. The seroconversion rate in the 12-23 months age group was 97.9-100.0% for measles, 85.1-88.9% for mumps and 100.0% for rubella. All children 4-6 years of age previously seronegative showed seroconversion for measles, mumps and rubella. Local adverse events were reported in 8.3-16.1% (12-23 months age) and 27.8-31.6% (4-6 years age), and 40.0-48.2% (12-23 months age) and 42.1-61.1% (4-6 years age) experienced at least more than 1 systemic adverse reaction. No vaccine-related serious adverse events were reported. Among the same age groups, there was no significant difference in adverse events between the two vaccines. CONCLUSION: The MMR vaccines are safe and show good immunogenic responses in children. These data will be invaluable when we introduce diverse vaccines in the following future.

Population-based case-control study of measles, mumps, and rubella and inflammatory bowel disease.

BACKGROUND: Previous controversy was generated over the hypothesis that a paramyxovirus such as measles or vaccination against such viruses might be causally associated with inflammatory bowel disease (IBD). We aimed to determine if Crohn's disease (CD) or ulcerative colitis (UC) subjects are more likely to be seropositive for measles, mumps, or rubella than controls. METHODS: Using our population-based University of Manitoba IBD Research Registry we recruited CD (n = 235) and UC (n = 137) subjects ages 18-50 years for a study involving detailed questionnaires and venipuncture. We accessed the population-based databases of Manitoba Health (single provincial health insurer) to get age-, gender-, and geography-matched non-IBD controls (n = 310). We used a standard enzyme-linked immunosorbent assay (ELISA) to measure serum antibodies. RESULTS: Seropositivity for measles and mumps was similar in controls (98.1%, 78.4%, respectively) as in CD (96.2%, 72.3% respectively) and in UC (95.5%, 74.6%, respectively). However, controls were significantly more likely to be seropositive for rubella (98.1%) than were CD cases (91.0%, P < 0.0002) or UC cases (93.3%, P = 0.01). Males accounted for the significantly lower rates of seropositivity to rubella with CD. While we determined that significantly more controls than CD were vaccinated, we cannot be sure if the increased rate of rubella seropositivity in controls is secondary to wildtype or vaccine-associated infection. CONCLUSIONS: These data suggest there is no association of having acquired measles, mumps, or rubella (by natural infection or through vaccination) and CD or UC. If anything, these data may suggest some protective effect of having acquired rubella infection or vaccine against acquiring CD.

Combination vaccines.

Recently multiple individual vaccines were put together into one syringe. This is ideal to simplify the administration of vaccines and reduce emotional distress from multiple injections. However, combination of many vaccines may interfere with the properties of each individual antigen and complicate the schedule. From earlier studies, most of the combinations of diphtheria-tetanus-pertussis (whole-cell) vaccine (DTPw), Haemophilus influenzae type b vaccine (Hib), hepatitis B vaccine (HBV), and inactivated polio vaccine (IPV) were safe and adequately immunogenic. On the other hand, there was a notable reduction in anti-PRP when Hib was combined with acellular pertussis vaccine (DTPa). Combination of hepatitis A vaccine and HBV was safe and effective. Those coming soon in the pipeline are DTPa-Hib-HBV, MMR-varicella, pneumococcal-meningococcal. With the increase in demand, health-care providers need to be acquainted to these combination vaccines. The bottom line is to make sure that the children get vaccination appropriately.