Maintained partial protection against Streptococcus pneumoniae despite B-cell depletion in mice vaccinated with a pneumococcal glycoconjugate vaccine.
Maintained partial protection against Streptococcus pneumoniae despite B-cell depletion in mice vaccinated with a pneumococcal glycoconjugate vaccine.
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DOI：
10.1002/cti2.1366
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发表时间：
2022
影响因子：
5.8
通讯作者：
Brown JS
中科院分区：
文献类型：
--
作者：
Ercoli G;Ramos-Sevillano E;Pearce E;Ragab S;Goldblatt D;Weckbecker G;Brown JS
抗CD20单抗治疗迅速耗尽循环中95%的CD20+B细胞 。B细胞耗尽是治疗自身免疫性疾病和B细胞恶性肿瘤的有效方法，但也会增加呼吸道感染的风险。这种对获得性免疫的影响可以通过接种疫苗来抵消。我们使用小鼠模型来研究B细胞耗尽对肺炎球菌疫苗接种的影响，包括对感染的保护和疫苗接种的时间与B细胞耗尽的关系。用抗CD20抗体去除C57BL/6雌性小鼠的B细胞，并在抗CD20治疗前和治疗后分别接种两种剂量的Prevnar-13疫苗。采用全细胞酶联免疫吸附试验和流式细胞仪抗体结合试验检测B细胞谱和肺炎链球菌特异性免疫球蛋白。通过用肺炎链球菌(S. )肺炎模型攻击小鼠来评估疫苗诱导的保护作用。对肺炎链球菌(S. )的抗体反应在接种后耗尽的小鼠B细胞中基本保持不变，从而对肺炎球菌感染具有充分的保护作用。相比之下，接种Prevnar-13的小鼠在B细胞耗尽(B细胞数量减少90%)的情况下，循环中抗 肺炎沙门氏菌Ig G和Ig M水平(用ELISA法和流式细胞仪抗体结合分析测定)降低。然而，一些抗体反应保持了下来，尽管疫苗诱导的对肺炎链球菌感染的保护受到了损害，但仍有50%的挑战小鼠预防了败血症。这项研究表明，尽管在B细胞严重枯竭期间疫苗的效力受到损害，但仍保留了一些保护效力，这表明接种疫苗仍然是有益的。B细胞耗尽患者接种肺炎球菌疫苗的时机对疫苗效果至关重要。这项研究表明，虽然只有在耗尽之前给小鼠接种疫苗才能确保完全保护，但耗尽期间/耗尽后接种疫苗也可以提供一定程度的对S. 肺炎的免疫力。
Anti‐CD20 monoclonal antibody therapy rapidly depletes > 95% of CD20+ B cells from the circulation. B‐cell depletion is an effective treatment for autoimmune disease and B‐cell malignancies but also increases the risk of respiratory tract infections. This effect on adaptive immunity could be countered by vaccination. We have used mouse models to investigate the effects of B‐cell depletion on pneumococcal vaccination, including protection against infection and timing of vaccination in relation to B‐cell depletion. C57BL/6 female mice were B‐cell depleted using anti‐CD20 antibody and immunized with two doses of Prevnar‐13 vaccine either before or after anti‐CD20 treatment. B‐cell repertoire and Streptococcus pneumoniae–specific IgG levels were measured using whole‐cell ELISA and flow cytometry antibody‐binding assay. Protection induced by vaccination was assessed by challenging the mice using a S. pneumoniae pneumonia model. Antibody responses to S. pneumoniae were largely preserved in mice B‐cell depleted after vaccination resulting in full protection against pneumococcal infections. In contrast, mice vaccinated with Prevnar‐13 while B cells were depleted (with > 90% reduction in B‐cell numbers) had decreased circulating anti–S. pneumoniae IgG and IgM levels (measured using ELISA and flow cytometry antibody binding assays). However, some antibody responses were maintained, and, although vaccine‐induced protection against S. pneumoniae infection was impaired, septicaemia was still prevented in 50% of challenged mice. This study showed that although vaccine efficacy during periods of profound B‐cell depletion was impaired some protective efficacy was preserved, suggesting that vaccination remains beneficial. Timing of pneumococcal vaccination in B‐cell–depleted patients is critical for vaccine efficacy. This study shows that, although full protection can only be ensured by vaccinating mice before depletion, vaccination during/after depletion can also provide a degree of immunity against S. pneumoniae.
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DOI：
10.1093/infdis/jis212
发表时间：
2012-05-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Clutterbuck EA;Lazarus R;Yu LM;Bowman J;Bateman EA;Diggle L;Angus B;Peto TE;Beverley PC;Mant D;Pollard AJ
通讯作者：
Pollard AJ
影响因子：
9.1
作者：
Eisenberg RA;Jawad AF;Boyer J;Maurer K;McDonald K;Prak ET;Sullivan KE
通讯作者：
Sullivan KE
影响因子：
9.2
作者：
Reglinski M;Ercoli G;Plumptre C;Kay E;Petersen FC;Paton JC;Wren BW;Brown JS
通讯作者：
Brown JS
影响因子：
7.3
作者：
Ercoli G;Ramos-Sevillano E;Nakajima R;de Assis RR;Jasinskas A;Goldblatt D;Felgner P;Weckbecker G;Brown J
通讯作者：
Brown J
影响因子：
--
作者：
Dixon, W. G.;Watson, K.;Symmons, D. P. M.
通讯作者：
Symmons, D. P. M.