Heterogeneity in Vaccinal Immunity to SARS-CoV-2 Can Be Addressed by a Personalized Booster Strategy.
Heterogeneity in Vaccinal Immunity to SARS-CoV-2 Can Be Addressed by a Personalized Booster Strategy.
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DOI：
10.3390/vaccines11040806
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发表时间：
2023-04-06
期刊：
影响因子：
7.8
通讯作者：
Chakravarty A
中科院分区：
文献类型：
--
作者：
Stoddard M;Yuan L;Sarkar S;Mangalaganesh S;Nolan RP;Bottino D;Hather G;Hochberg NS;White LF;Chakravarty A
SARS-CoV-2 疫苗最初被证明可以大大降低严重疾病和死亡的风险。然而，药代动力学 (PK) 减弱和病毒快速进化会降低中和抗体 (nAb) 结合滴度，导致疫苗保护作用丧失。此外，疫苗 nAb 反应的强度和持久性存在个体间异质性。在这里，我们提出了个性化的助推器策略作为该问题的潜在解决方案。我们基于模型的方法将 SARS-CoV-2 初次疫苗接种反应中的个体间异质性纳入药代动力学/药效学 (PK/PD) 模型中，以预测疫苗保护中人群水平的异质性。我们根据 nAb 效力的变异倍数降低，进一步研究了随着时间的推移，进化免疫逃避对疫苗保护的影响。我们的研究结果表明，病毒进化将降低疫苗预防严重疾病的有效性，特别是对于免疫反应较不持久的个体。更频繁地加强免疫可能会恢复对免疫反应较弱的个体的疫苗保护。我们的分析表明，ECLIA RBD 结合测定强烈预测序列匹配的假病毒的中和。这可能是快速评估个体免疫保护的有用工具。我们的工作表明，针对严重疾病的疫苗保护并不确定，并确定了降低免疫脆弱个体风险的潜在途径。
SARS-CoV-2 vaccinations were initially shown to substantially reduce risk of severe disease and death. However, pharmacokinetic (PK) waning and rapid viral evolution degrade neutralizing antibody (nAb) binding titers, causing loss of vaccinal protection. Additionally, there is inter-individual heterogeneity in the strength and durability of the vaccinal nAb response. Here, we propose a personalized booster strategy as a potential solution to this problem. Our model-based approach incorporates inter-individual heterogeneity in nAb response to primary SARS-CoV-2 vaccination into a pharmacokinetic/pharmacodynamic (PK/PD) model to project population-level heterogeneity in vaccinal protection. We further examine the impact of evolutionary immune evasion on vaccinal protection over time based on variant fold reduction in nAb potency. Our findings suggest viral evolution will decrease the effectiveness of vaccinal protection against severe disease, especially for individuals with a less durable immune response. More frequent boosting may restore vaccinal protection for individuals with a weaker immune response. Our analysis shows that the ECLIA RBD binding assay strongly predicts neutralization of sequence-matched pseudoviruses. This may be a useful tool for rapidly assessing individual immune protection. Our work suggests vaccinal protection against severe disease is not assured and identifies a potential path forward for reducing risk to immunologically vulnerable individuals.
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DOI：
10.2807/1560-7917.es.2022.27.18.2200322
发表时间：
2022-05
期刊：
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin
影响因子：
--
作者：
通讯作者：
--
DOI：
10.3390/v12121390
发表时间：
2020-12-04
期刊：
Viruses
影响因子：
--
作者：
Hashem AM;Algaissi A;Almahboub SA;Alfaleh MA;Abujamel TS;Alamri SS;Alluhaybi KA;Hobani HI;AlHarbi RH;Alsulaiman RM;ElAssouli MZ;Hala S;Alharbi NK;Alhabbab RY;AlSaieedi AA;Abdulaal WH;Bukhari A;Al-Somali AA;Alofi FS;Khogeer AA;Pain A;Alkayyal AA;Almontashiri NAM;Ahmad BM;Li X
通讯作者：
Li X
影响因子：
9.4
作者：
Addetia A;Crawford KHD;Dingens A;Zhu H;Roychoudhury P;Huang ML;Jerome KR;Bloom JD;Greninger AL
通讯作者：
Greninger AL
影响因子：
64.5
作者：
Garcia-Beltran, Wilfredo F.;St Denis, Kerri J.;Balazs, Alejandro B.
通讯作者：
Balazs, Alejandro B.
影响因子：
13.8
作者：
De Marco, Lorenzo;D'Orso, Silvia;Pirronello, Marta;Verdiani, Alice;Termine, Andrea;Fabrizio, Carlo;Capone, Alessia;Sabatini, Andrea;Guerrera, Gisella;Placido, Roberta;Sambucci, Manolo;Angelini, Daniela F.;Giannessi, Flavia;Picozza, Mario;Caltagirone, Carlo;Salvia, Antonino;Volpe, Elisabetta;Balice, Maria Pia;Rossini, Angelo;Rotzschke, Olaf;Giardina, Emiliano;Battistini, Luca;Borsellino, Giovanna
通讯作者：
Borsellino, Giovanna