دورية أكاديمية
Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM197 conjugate vaccine
| العنوان: | Short Vi-polysaccharide abrogates T-independent immune response and hyporesponsiveness elicited by long Vi-CRM197 conjugate vaccine |
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| المؤلفون: | Micoli, F, Bjarnarson, SP, Arcuri, M, Aradottir Pind, AA, Magnusdottir, GJ, Necchi, F, Di Benedetto, R, Carducci, M, Schiavo, F, Giannelli, C, Pisoni, I, Martin, LB, Del Giudice, G, MacLennan, CA, Rappuoli, R, Jonsdottir, I, Saul, A |
| بيانات النشر: | National Academy of Sciences |
| سنة النشر: | 2021 |
| المجموعة: | Oxford University Research Archive (ORA) |
| الوصف: | Polysaccharide-protein conjugates have been developed to overcome the T-independent response, hyporesponsiveness to repeated vaccination, and poor immunogenicity in infants of polysaccharides. To address the impact of polysaccharide length, typhoid conjugates made with short- and long-chain fractions of Vi polysaccharide with average sizes of 9.5, 22.8, 42.7, 82.0, and 165 kDa were compared. Long-chain-conjugated Vi (165 kDa) induced a response in both wild-type and T cell-deficient mice, suggesting that it maintains a T-independent response. In marked contrast, short-chain Vi (9.5 to 42.7 kDa) conjugates induced a response in wild-type mice but not in T cell-deficient mice, suggesting that the response is dependent on T cell help. Mechanistically, this was explained in neonatal mice, in which long-chain, but not short-chain, Vi conjugate induced late apoptosis of Vi-specific B cells in spleen and early depletion of Vi-specific B cells in bone marrow, resulting in hyporesponsiveness and lack of long-term persistence of Vi-specific IgG in serum and IgG + antibody-secreting cells in bone marrow. We conclude that while conjugation of long-chain Vi generates T-dependent antigens, the conjugates also retain T-independent properties, leading to detrimental effects on immune responses. The data reported here may explain some inconsistencies observed in clinical trials and help guide the design of effective conjugate vaccines. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://ora.ox.ac.uk/objects/uuid:f0f6dc4c-2a6b-4941-ad8f-78d5ceed3686Test; https://doi.org/10.1073/pnas.2005857117Test |
| DOI: | 10.1073/pnas.2005857117 |
| الإتاحة: | https://doi.org/10.1073/pnas.2005857117Test https://ora.ox.ac.uk/objects/uuid:f0f6dc4c-2a6b-4941-ad8f-78d5ceed3686Test |
| حقوق: | info:eu-repo/semantics/openAccess ; CC Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) |
| رقم الانضمام: | edsbas.B3C85B0F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1073/pnas.2005857117 |
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