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Humoral responses to the measles, mumps and rubella vaccine are impaired in Leigh Syndrome French Canadian patients.

ABSTRACT: Leigh Syndrome French Canadian (LSFC) is a rare autosomal recessive metabolic disorder characterized by severe lactic acidosis crises and early mortality. LSFC patients carry mutations in the Leucine Rich Pentatricopeptide Repeat Containing (LRPPRC) gene, which lead to defects in the respiratory chain complexes and mitochondrial dysfunction. Mitochondrial respiration modulates cellular metabolic activity, which impacts many cell types including the differentiation and function of immune cells. Hence, we postulated that, in addition to neurological and metabolic disorders, LSFC patients may show impaired immune activity. To gain insight into the quality of the immune response in LSFC patients, we examined the response to the measles, mumps and rubella (MMR) vaccine by measuring antibody titers to MMR in the plasma. In a cohort of eight LSFC patients, the response to the MMR vaccine was variable, with some individuals showing antibodies to all three viruses, while others had antibodies to two or fewer viruses. These results suggest that the mutations in the LRPPRC gene present in LSFC patients may affect the immune response to vaccines. Monitoring vaccine response in this fragile population should be considered to ensure full protection against pathogens.

SUBMITTER: Fois A

PROVIDER: S-EPMC7577467 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Humoral responses to the measles, mumps and rubella vaccine are impaired in Leigh Syndrome French Canadian patients.

Fois Adrien A Boucher-Lafleur Anne-Marie AM Thompson Legault Julie J Renaud Christian C Morin Charles C Des Rosiers Christine C Coderre Lise L Laprise Catherine C Lesage Sylvie S

PloS one 20201021 10

Leigh Syndrome French Canadian (LSFC) is a rare autosomal recessive metabolic disorder characterized by severe lactic acidosis crises and early mortality. LSFC patients carry mutations in the Leucine Rich Pentatricopeptide Repeat Containing (LRPPRC) gene, which lead to defects in the respiratory chain complexes and mitochondrial dysfunction. Mitochondrial respiration modulates cellular metabolic activity, which impacts many cell types including the differentiation and function of immune cells. H ...[more]

PMID: 33085679

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Project description:In the U.S., measles, mumps, and rubella vaccination is recommended as two vaccine doses. A third dose of measles-mumps-rubella (MMR) vaccine is being administered in certain situations (e.g., identified seronegativity and during outbreaks). We studied rubella-specific humoral immunity (neutralizing antibody, enzyme-linked immunosorbent assay/ELISA IgG titer and antibody avidity) and the frequencies of antigen-specific memory B cells before and after a third dose of MMR-II in 109 female participants of childbearing age (median age, 34.5 years old) from Olmsted County, MN, with two documented prior MMR vaccine doses. The participants were selected from a cohort of 1117 individuals if they represented the high and the low ends of the rubella-specific antibody response spectrum. Of the 109 participants, we identified four individuals (3.67% of all study participants; 7.14% of the low-responder group) that were seronegative at Baseline (rubella-specific ELISA IgG titers <10 IU/mL), suggesting a lack of protection against rubella before receipt of a third MMR vaccine dose. The peak geometric mean neutralizing antibody titer one month following the third dose of MMR vaccine for the cohort was 243 NT50 (CI; 241, 245), which is expected for a cohort with two doses of MMR, and the peak geometric mean IgG titer was 150 IU/mL (CI; 148, 152) with no seronegative individuals at Day 28. One-third of all subjects (31.8% for the neutralizing antibody; 30.8% for the IgG titer) experienced a significant boost (≥4-fold) of antibody titers one month following vaccination. Antibody titers and other tested immune-response variables were significantly higher in the high-responder group compared to the low-responder group. The frequencies of rubella-specific memory B cells were modestly associated with the antibody titers. Our study suggests the importance of yet unknown inherent biologic and immune factors for the generation and maintenance of rubella-vaccine-induced humoral immune responses.

Project description:BackgroundThe reported coverage of the measles-rubella (MR) or measles-mumps-rubella (MMR) vaccine is greater than 99.0% in Zhejiang province. However, the incidence of measles, mumps, and rubella remains high. In this study, we assessed MMR seropositivity and disease distribution by age on the basis of the current vaccination program, wherein the first dose of MR is administered at 8 months and the second dose of MMR is administered at 18-24 months.MethodsCross-sectional serological surveys of MMR antibodies were conducted by collecting epidemiological data in Zhejiang province, China in 2011. In total, 1015 participants were randomly selected from two surveillance sites. Serum MMR-specific immunoglobulin G levels were tested by enzyme-linked immunosorbent assay. The geometric mean titers and seroprevalence with 95% confidence intervals (CIs) were calculated by age and gender. Proportions of different dose of vaccine by age by vaccine were also identified. Statistically significant differences between categories were assessed by the Chi-square test.ResultsOver 95% seroprevalence rates of measles were seen in all age groups except <7 months infants. Children aged 5-9 years were shown lower seropositivity rates of mumps while elder adolescences and young adults were presented lower rubella seroprevalence. Especially, rubella seropositivity was significantly lower in female adults than in male. Nine measles cases were unvaccinated or unknown vaccination history. Among them, 66.67% (6/9) patients were aged 20-29 years while 33.33% (3/9) were infants aged 8-12 months. In addition, 57.75% (648/1122) patients with mumps were children aged 5-9 years, and 50.54% (94/186) rubella cases were aged 15-39 years.ConclusionsA timely two-dose MMR vaccination schedule is recommended, with the first dose at 8 months and the second dose at 18-24 months. An MR vaccination speed-up campaign may be necessary for elder adolescents and young adults, particularly young females.

Dataset Information

Humoral responses to the measles, mumps and rubella vaccine are impaired in Leigh Syndrome French Canadian patients.

Publications

Humoral responses to the measles, mumps and rubella vaccine are impaired in Leigh Syndrome French Canadian patients.

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