CD46 measles virus receptor polymorphisms influence receptor protein expression and primary measles vaccine responses in naive australian children

Despite the availability of measles vaccines, infants continue to die from measles. Measles vaccine responses vary between individuals, and poor immunogenicity is likely to preclude protection against measles. CD46 is a ubiquitously expressed specific receptor for vaccine strains of measles virus. C...

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Main Authors: Clifford, H., Hayden, C., Khoo, S., Zhang, Guicheng, Le Souëf, P., Richmonda, P.
Format: Journal Article
Published: 2012
Online Access:http://hdl.handle.net/20.500.11937/13870
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author Clifford, H.
Hayden, C.
Khoo, S.
Zhang, Guicheng
Le Souëf, P.
Richmonda, P.
author_facet Clifford, H.
Hayden, C.
Khoo, S.
Zhang, Guicheng
Le Souëf, P.
Richmonda, P.
author_sort Clifford, H.
building Curtin Institutional Repository
collection Online Access
description Despite the availability of measles vaccines, infants continue to die from measles. Measles vaccine responses vary between individuals, and poor immunogenicity is likely to preclude protection against measles. CD46 is a ubiquitously expressed specific receptor for vaccine strains of measles virus. CD46 polymorphisms have not been functionally investigated but may affect CD46 protein expression, which in turn may mediate primary measles antibody responses in infants. In a cohort of children aged 12 to 14 months from Perth, Australia (n=137), after their first dose of measles-mumps-rubella (MMR) vaccine, CD46 polymorphisms were genotyped, and postvaccination measles IgG and CD46 protein expression before and after measles lysate stimulation of cells were measured. Three CD46 variants (rs7144, rs11118580, and rs2724384) were significantly associated with measles virus-specific IgG levels (P=0.008, P=0.026, and P=0.018, respectively). There were significant differences between CD46 rs7144 genotypes and CD46 protein expression on T cells, as well as the downregulation of CD46 and T-cell frequency after measles lysate stimulation. We show that CD46 polymorphisms were associated with primary measles antibody responses in naive infants. We also report the first association of a measles virus receptor polymorphism with functional effects on the receptor, suggesting a possible mechanism through which antibody responses are altered. Elucidating all of the interconnecting genetic factors that alter primary measles vaccine responses may be important for identifying children at risk of poor immunogenicity or vaccine failure and for the future design of vaccine strategies to help these children. Copyright © 2012, American Society for Microbiology.
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spelling curtin-20.500.11937-138702017-09-13T15:01:03Z CD46 measles virus receptor polymorphisms influence receptor protein expression and primary measles vaccine responses in naive australian children Clifford, H. Hayden, C. Khoo, S. Zhang, Guicheng Le Souëf, P. Richmonda, P. Despite the availability of measles vaccines, infants continue to die from measles. Measles vaccine responses vary between individuals, and poor immunogenicity is likely to preclude protection against measles. CD46 is a ubiquitously expressed specific receptor for vaccine strains of measles virus. CD46 polymorphisms have not been functionally investigated but may affect CD46 protein expression, which in turn may mediate primary measles antibody responses in infants. In a cohort of children aged 12 to 14 months from Perth, Australia (n=137), after their first dose of measles-mumps-rubella (MMR) vaccine, CD46 polymorphisms were genotyped, and postvaccination measles IgG and CD46 protein expression before and after measles lysate stimulation of cells were measured. Three CD46 variants (rs7144, rs11118580, and rs2724384) were significantly associated with measles virus-specific IgG levels (P=0.008, P=0.026, and P=0.018, respectively). There were significant differences between CD46 rs7144 genotypes and CD46 protein expression on T cells, as well as the downregulation of CD46 and T-cell frequency after measles lysate stimulation. We show that CD46 polymorphisms were associated with primary measles antibody responses in naive infants. We also report the first association of a measles virus receptor polymorphism with functional effects on the receptor, suggesting a possible mechanism through which antibody responses are altered. Elucidating all of the interconnecting genetic factors that alter primary measles vaccine responses may be important for identifying children at risk of poor immunogenicity or vaccine failure and for the future design of vaccine strategies to help these children. Copyright © 2012, American Society for Microbiology. 2012 Journal Article http://hdl.handle.net/20.500.11937/13870 10.1128/CVI.05652-11 unknown
spellingShingle Clifford, H.
Hayden, C.
Khoo, S.
Zhang, Guicheng
Le Souëf, P.
Richmonda, P.
CD46 measles virus receptor polymorphisms influence receptor protein expression and primary measles vaccine responses in naive australian children
title CD46 measles virus receptor polymorphisms influence receptor protein expression and primary measles vaccine responses in naive australian children
title_full CD46 measles virus receptor polymorphisms influence receptor protein expression and primary measles vaccine responses in naive australian children
title_fullStr CD46 measles virus receptor polymorphisms influence receptor protein expression and primary measles vaccine responses in naive australian children
title_full_unstemmed CD46 measles virus receptor polymorphisms influence receptor protein expression and primary measles vaccine responses in naive australian children
title_short CD46 measles virus receptor polymorphisms influence receptor protein expression and primary measles vaccine responses in naive australian children
title_sort cd46 measles virus receptor polymorphisms influence receptor protein expression and primary measles vaccine responses in naive australian children
url http://hdl.handle.net/20.500.11937/13870