mina et al., science 1 november 2019 - unispital basel · the antibody repertoire and magnitude of...
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Mina et al., Science 1 November 2019
Journal Club Infektiologie 11.11.2019
Silvio Ragozzino
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Background
• Measles endemic in much of the world à >100,000 deaths yearly
• Increase in M&M for as long as 5 years after infection
• Since 2018 increased incidence as a result of reduced vaccination
• Importance of understanding consequences of measles virus infection
• Immunosuppression after measles:
Ø1908 Clemens von Pirquet: negative cutaneous tuberculin reaction in children
ØDecreased interferon signaling, skewed cytokine response, lymphopenia
ØMV receptor highly expressed on memory T, B, Plasma cells à «Immunological amnesia»
• Aim: identify and quantify effects of measles on the immune system
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Methods
• Paired blood samples from unimmunized children during a measles outbreak in the NetherlandsØchildren who developed measles (n=77)
Øuninfected children (n=5)
• Control cohortsØage-matched controls, sampled 3 months apart (n=28)
Øage-matched controls, sampled 1 year apart (n=31)
Øadult controls (n=22)
Øchildren before and after MMR vaccination (n=33)
o Mild measles (n=34)
o Severe measles (n=43)
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Methods
• VirScan: PhIP-Seq technology
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Methods
• Expanded VirScan Library
ØFull proteomes of most viruses
ØMany bacterial proteins
• Comprehensive measure of antibody repertoire diversity
• Epitope binding signal (EBS): a relative measure of antibody titer for
each epitope
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Results and discussion
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Antibody repertoire diversityCntl A: age-matched, 3 monthsCntl B: age-matched, 1 yearCntl C: healthy adults
Enterovirus
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Antibody repertoire diversity
• Mean reduction of 20% in the overall diversity or size of the antibody repertoire after MV infection
• Increase in MV-specific epitopes in children after measles or MMR vaccination
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• No changes in total IgG (ELISA)
• Restructuring of the antibody
repertoire after measles
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Effect on preexisting immune memory
• After severe or mild measles,children lost a median of 40% or33% respectively, of their totalpreexisting pathogen-specificantibody repertoires
• Controls retained 90% of their repertoires
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Effect on strength of epitope recognition
After measles 40% reductions in EBSs
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Effect of MMR vaccine on immune repertoire
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Reconstruction of the immune repertoire
• Subset of children with increased EBS for specific pathogens after
measles à New exposure?
• High transmissible respiratory pathogens
• Spatially clustered?
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Reconstruction of the immune repertoire
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Experimental measles infections
• 4 rhesus macaques• VirScan antibody profiling before and 5 months after measles
• Each monkey lost, on average, 40 to 60% of its preexisting antibody repertoire
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Conclusions
• Measles is associated with large reductions in both the diversity of
the antibody repertoire and magnitude of the binding signal
• Rebuilding of immune memory through reexposure à increased
clinical risks
• Measles vaccine does not impair immune repertoire, on the contrary,
prevents immune amnesia and reduces morbidity and mortality risks