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| ISV Paper of the Month |
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December 2011 |
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A mechanism for glycoconjugate vaccine activation
of the adaptive immune system and its implications for vaccine design |
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Fikri Y Avci, Xiangming Li, Moriya Tsuji & Dennis
L Kasper |
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Nature Medicine, Vol. 17, No. 12, 1602-1609 |
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Glycoconjugate vaccines have provided enormous health
benefits globally, but they have been less successful in some populations at high
risk for developing disease. To identify new approaches to enhancing glycoconjugate
effectiveness, we investigated molecular and cellular mechanisms governing the immune
response to a prototypical glycoconjugate vaccine. We found that in antigen-presenting
cells a carbohydrate epitope is generated upon endolysosomal processing of group
B streptococcal type III polysaccharide coupled to a carrier protein. In conjunction
with a carrier protein–derived peptide, this carbohydrate epitope binds major histocompatibility
class II (MHCII) and stimulates carbohydrate- specific CD4+ T cell clones to produce
interleukins 2 and 4—cytokines essential for providing T cell help to antibody-producing
B cells. An archetypical glycoconjugate vaccine that we constructed to maximize
the presentation of carbohydrate-specific T cell epitopes is 50–100 times more potent
and substantially more protective in a neonatal mouse model of group B Streptococcus
infection than a vaccine constructed by methods currently used by the vaccine industry.
Our discovery of how glycoconjugates are processed resulting in presentation of
carbohydrate epitopes that stimulate CD4+ T cells has key implications for glycoconjugate
vaccine design that could result in greatly enhanced vaccine efficacy. |
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Also see a related N&V article: |
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A sweet T cell response |
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Rino Rappuoli & Ennio De Gregorio |
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Nature Medicine, Vol. 17, No. 12, 1551-1552 |
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Although protein-polysaccharide conjugate vaccines provide notable clinical benefits,
it is still not fully understood how they work. A new mechanism of action for these
vaccines has been identified in which T cells can recognize sugar epitopes in the
context of the major histocompatibility complex (MHC) provided they are bound to
a protein ‘anchor’, which allows binding of the sugar epitope to the MHC |
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