Vaccination in patients with kidney failure: lessons from COVID-19.
Vaccination in patients with kidney failure: lessons from COVID-19.
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DOI：
10.1038/s41581-022-00617-5
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发表时间：
2022-11
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影响因子：
--
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感染是慢性肾脏病(CKD)患者的第二大死亡原因。需要足够的体液(抗体)和细胞(T细胞驱动)免疫，以最大限度地减少病原体进入，促进病原体清除，从而实现感染控制。疫苗接种可以产生对特定病原体的细胞和体液免疫，并用于预防许多危及生命的传染病。然而，CKD患者的疫苗接种效果会减弱。免疫系统的过早老化和慢性全身低度炎症是这些患者免疫改变的主要原因。在SARS-CoV-2感染的情况下，新冠肺炎对慢性肾脏病患者，特别是肾功能衰竭患者有相当大的有害影响。因此，通过成功接种疫苗来预防新冠肺炎对这一脆弱人群至关重要。尽管接受透析的患者的血清转换率与肾功能正常的患者相当，但大多数肾移植受者在接种两剂新冠肺炎疫苗后无法产生体液免疫。重要的是，一些不能产生抗体的患者仍然有可检测到的疫苗特异性T细胞反应，这可能足以预防严重的新冠肺炎。对于肾衰竭患者，尚未建立预防SARS-CoV-2的相关性，但迫切需要它们来实现个性化疫苗接种方案。有效的疫苗接种策略对于降低肾衰竭患者感染相关发病率和死亡率的高风险至关重要。在这里，作者检查了这些患者的疫苗诱导免疫，特别是他们对新冠肺炎疫苗接种的反应，在肾功能障碍和免疫抑制药物使用导致的免疫损伤的背景下。慢性肾脏病(CKD)患者由于CKD相关的免疫系统过早老化和慢性全身性低度炎症，疫苗接种反应减弱。体液免疫(B细胞驱动)和细胞免疫(T细胞驱动)通常都是控制感染所必需的。抗体在预防病毒感染方面特别有效，而T细胞在清除病毒和帮助预防严重疾病方面发挥关键作用。即使在因原发或继发免疫缺陷而不能产生抗体的患者中，也能检测到针对SARS-CoV-2刺突蛋白的T细胞反应。肾小球滤过率与新冠肺炎的严重程度相关-在肾脏疾病患者中，肾功能衰竭患者的新冠肺炎预后最差。还没有为肾衰竭患者建立预防SARS-CoV-2的相关性，但迫切需要它们来实现个性化的疫苗接种方案。无反应或低反应的患者应该被确定为有针对性的额外加强剂量或使用单抗进行预防性治疗。肾功能衰竭患者的疫苗反应也可能通过使用更高剂量的疫苗、佐剂或皮内接种来增加；在接种疫苗之前暂时减少免疫抑制药物也可能是可行的。
Infection is the second leading cause of death in patients with chronic kidney disease (CKD). Adequate humoral (antibody) and cellular (T cell-driven) immunity are required to minimize pathogen entry and promote pathogen clearance to enable infection control. Vaccination can generate cellular and humoral immunity against specific pathogens and is used to prevent many life-threatening infectious diseases. However, vaccination efficacy is diminished in patients with CKD. Premature ageing of the immune system and chronic systemic low-grade inflammation are the main causes of immune alteration in these patients. In the case of SARS-CoV-2 infection, COVID-19 can have considerable detrimental effects in patients with CKD, especially in those with kidney failure. COVID-19 prevention through successful vaccination is therefore paramount in this vulnerable population. Although patients receiving dialysis have seroconversion rates comparable to those of patients with normal kidney function, most kidney transplant recipients could not generate humoral immunity after two doses of the COVID-19 vaccine. Importantly, some patients who were not able to produce antibodies still had a detectable vaccine-specific T cell response, which might be sufficient to prevent severe COVID-19. Correlates of protection against SARS-CoV-2 have not been established for patients with kidney failure, but they are urgently needed to enable personalized vaccination regimens. Effective vaccination strategies are crucial to mitigate the high risk of infection-associated morbidity and mortality in patients with kidney failure. Here, the authors examine vaccine-induced immunity in these patients, in particular their responses to COVID-19 vaccination, in the context of the immune impairment induced by kidney dysfunction and the use of immunosuppressive medications. Patients with chronic kidney disease (CKD) have diminished vaccination responses owing to CKD-associated premature ageing of the immune system and chronic systemic low-grade inflammation. Both humoral (B cell-driven) and cellular (T cell-driven) immunity are generally required to control infections. Antibodies are particularly efficient in preventing viral infections, whereas T cells have a key role in viral clearance and help to prevent severe disease. T cell responses against the SARS-CoV-2 spike protein can be detected even in patients who are not able to produce antibody owing to primary or secondary immune deficiency. The glomerular filtration rate correlates with the severity of COVID-19 — among patients with kidney disease, the worst COVID-19 outcomes are observed in patients with kidney failure. Correlates of protection against SARS-CoV-2 have not been established for patients with kidney failure but they are urgently needed to enable personalized vaccination regimens. Patients with absent or low responses should be identified for targeted additional booster doses or pre-emptive therapy with monoclonal antibodies. Vaccine responses in patients with kidney failure might also be increased through the use of higher vaccine doses, adjuvants or intradermal vaccination; temporary reduction of immunosuppressive drugs before vaccination might also be feasible.
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影响因子：
6.1
作者：
Bertrand, Dominique;Chavarot, Nathalie;Guerrot, Dominique
通讯作者：
Guerrot, Dominique
影响因子：
13.2
作者：
Barraclough, Katherine A.;Wiggins, Kathryn J.;Playford, E. Geoffrey
通讯作者：
Playford, E. Geoffrey
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
影响因子：
19.6
作者：
Benotmane I;Bruel T;Planas D;Fafi-Kremer S;Schwartz O;Caillard S
通讯作者：
Caillard S
影响因子：
4.4
作者：
Boonstra, A;Barrat, FJ;O'Garra, A
通讯作者：
O'Garra, A