Mechanistic model for booster doses effectiveness in healthy, cancer, and immunosuppressed patients infected with SARS-CoV-2.
Mechanistic model for booster doses effectiveness in healthy, cancer, and immunosuppressed patients infected with SARS-CoV-2.
复制标题
DOI：
10.1073/pnas.2211132120
复制
发表时间：
2023-01-17
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
目前的SARS-CoV-2疫苗在预防COVID-19或限制健康个体的疾病严重程度方面是有效的，但在癌症或免疫抑制患者中的有效性较低。在这里，我们通过建立我们的数学框架来解释疫苗诱导的免疫力，来解决随着时间的推移预测疫苗有效性的需求。两种mRNA疫苗的加强剂量可以诱导抗体水平和相关类型的适应性免疫细胞数量的稳健增强，预计这在健康患者中提供超过1年的足够保护。然而，我们的模型表明，对于免疫抑制的人或接受免疫抑制治疗的癌症患者，增强效应可能会减弱，应该更频繁地给予增强剂。SARS-CoV-2疫苗在限制疾病严重程度方面是有效的，但在患有癌症或免疫抑制的患者中效果较低。有效性随着时间的推移而减弱，并因疫苗类型而异。此外，以前规定的疫苗是基于祖先的SARS-CoV-2刺突蛋白，新出现的变种可能会逃避。在这里，我们描述了一个机制的数学模型接种疫苗诱导的免疫力。我们用现有的临床数据对其进行了验证，并使用它来模拟疫苗对各种疫苗平台的抗原性较低、毒力增加或细胞结合增强的病毒变体的有效性。该分析包括omicron变体以及假设的未来变体，这些变体对疫苗诱导的抗体具有更大的免疫逃避，并解决了新二价疫苗的潜在益处。我们进一步解释并发癌症或潜在的免疫抑制。该模型证实了免疫抑制患者加强接种疫苗后免疫原性增强，但预测这些个体持续需要加强接种以维持保护。我们进一步研究了变异对免疫抑制个体的影响，作为多次加强剂量之间间隔的函数。我们的模型为未来的疫苗接种提出了可能的策略，并为高危人群提出了量身定制的策略。
Current SARS-CoV-2 vaccines are effective at preventing COVID-19 or limiting disease severity in healthy individuals, but effectiveness is lower among patients with cancer or immunosuppression. Here, we address the need for predictions of vaccine effectiveness over time by building on our mathematical framework to account for vaccination-induced immunity. A booster dose of both mRNA vaccines can induce a robust enhancement of both antibody levels and numbers of pertinent types of adaptive immune cells, which is predicted to provide sufficient protection for more than 1 y in healthy patients. However, our model suggests that for immunosuppressed people or patients with cancer receiving an immunosuppressive treatment, the booster effect may wane and should be given boosters on a more frequent basis. SARS-CoV-2 vaccines are effective at limiting disease severity, but effectiveness is lower among patients with cancer or immunosuppression. Effectiveness wanes with time and varies by vaccine type. Moreover, previously prescribed vaccines were based on the ancestral SARS-CoV-2 spike-protein that emerging variants may evade. Here, we describe a mechanistic mathematical model for vaccination-induced immunity. We validate it with available clinical data and use it to simulate the effectiveness of vaccines against viral variants with lower antigenicity, increased virulence, or enhanced cell binding for various vaccine platforms. The analysis includes the omicron variant as well as hypothetical future variants with even greater immune evasion of vaccine-induced antibodies and addresses the potential benefits of the new bivalent vaccines. We further account for concurrent cancer or underlying immunosuppression. The model confirms enhanced immunogenicity following booster vaccination in immunosuppressed patients but predicts ongoing booster requirements for these individuals to maintain protection. We further studied the impact of variants on immunosuppressed individuals as a function of the interval between multiple booster doses. Our model suggests possible strategies for future vaccinations and suggests tailored strategies for high-risk groups.
登录
查看更多内容
DOI：
10.1016/j.medj.2021.11.004
发表时间：
2021-12-10
期刊：
Med (New York, N.Y.)
影响因子：
--
作者：
Chen RE;Gorman MJ;Zhu DY;Carreño JM;Yuan D;VanBlargan LA;Burdess S;Lauffenburger DA;Kim W;Turner JS;Droit L;Handley SA;Chahin S;Deepak P;O'Halloran JA;Paley MA;Presti RM;Wu GF;Krammer F;Alter G;Ellebedy AH;Kim AHJ;Diamond MS
通讯作者：
Diamond MS
影响因子：
7.3
作者：
Garg AK;Mittal S;Padmanabhan P;Desikan R;Dixit NM
通讯作者：
Dixit NM
影响因子：
13.8
作者：
Lassauniere, Ria;Polacek, Charlotta;Frische, Anders;Boding, Lasse;Saekmose, Susanne Gjorup;Rasmussen, Morten;Fomsgaard, Anders
通讯作者：
Fomsgaard, Anders
影响因子：
50.3
作者：
Naranbhai V;St Denis KJ;Lam EC;Ofoman O;Garcia-Beltran WF;Mairena CB;Bhan AK;Gainor JF;Balazs AB;Iafrate AJ;CANVAX team
通讯作者：
CANVAX team
影响因子：
13.8
作者：
Kamar N;Abravanel F;Marion O;Romieu-Mourez R;Couat C;Del Bello A;Izopet J
通讯作者：
Izopet J