A causal multiomics study discriminates the early immune features of Ad5-vectored Ebola vaccine recipients

The vaccine-induced innate immune response is essential for the generation of an antibody response.To date,how Ad5-vectored vaccines are influenced by preexisting anti-Ad5 antibodies during activation of the early immune response remains unclear.Here,we investigated the specific alterations in GP1,2-specific IgG-related elements of the early immune response at the genetic,molecular,and cellular levels on days 0,1,3,and 7 after Ad5-EBOV vaccination.In a causal multiomics analysis,distinct early immune responses associated with GP1,2-specific IgG were observed in Ad5-EBOV recipients with a low level of preexisting anti-Ad5 antibodies.This study revealed the correlates of the Ad5-EBOV-induced IgG response and provided mechanistic evidence for overcoming preexisting Ad5 immunity during the administration of Ad5-vectored vaccines.

利用回归模型筛选出近天然的抗原-抗体对接模拟结构

在抗原-抗体分子对接模拟所生成的大量计算生成构象中筛选出近天然结构,即接近真实情况的抗原-抗体结合模式。借鉴QSAR原理,定义抗原-抗体接触面描述符并利用Discovery Studio 4.5软件平台计算出各对接模拟构象的接触面描述符和能量参数。构造训练集数据进行回归分析,建立预测对接模拟构象是否是近天然结构的数学模型。通过测试集和实际应用情况检验该数学模型。通过回归分析所建立的数学模型能够在成百上千的抗原-抗体对接模拟构象中有效筛选出其中的近天然结构,在测试集验证和4G7抗体结合模式预测应用中具有良好的表现,验证了该数学模型的有效性和实用性。经验性的抗原-抗体接触面特征如氢键密度、氨基酸对偏好性指数等以及能量参数能够共同有效表征近天然结构,所建立的数学模型有效增强了通过分子对接预测抗原-抗体结合模式的可行性。

Comparative characterization of antibody responses induced by Ad5-vectored spike proteins of emerging SARS-CoV-2 VOCs

Highly divergent SARS-CoV-2 variants have continuously emerged and spread around the world,and updated vaccines and innovative vaccination strategies are urgently needed to address the global SARS-COV2 pandemic.Here,we established a series of Ad5-vectored SARS-CoV-2 variant vaccines encoding multiple spike proteins derived from the Alpha,Beta,Gamma,Epsilon,Kappa,Delta and Omicron lineages and analyzed the antibody immune responses induced by single-dose and prime-boost vaccination strategies against emerging SARS-CoV-2 variants of concern(VOCs).Single-dose vaccination with SARS-CoV-2 variant vaccines tended to elicit the optimal self-matched neutralizing effects,and Ad5-B.1.351 produced more broad-spectrum cross-neutralizing antibodies against diverse variants.In contrast,prime-boost vaccination further strengthened and broadened the neutralizing antibody responses against highly divergent SARS-CoV-2 variants.The heterologous administration of Ad5-B.1.617.2 and Ad5-B.1.429 to Ad5-WT-primed mice resulted in superior antibody responses against most VOCs.In particular,the Omicron spike could only stimulate self-matched neutralizing antibodies with infrequent cross-reactivities to other variants used in single-dose vaccination strategies;moreover,with prime-boost regimens,this vaccine elicited an optimal specific neutralizing antibody response to Omicron,and prompted cross-antibody responses against other VOCs that were very similar to those obtained with Ad5-WT booster.Overall,this study delineated the unique characteristics of antibody responses to the SARS-CoV-2 VOC spikes with the single-dose or prime-boost vaccination strategies and provided insight into the vaccine development of next SARS-CoV-2 VOCs.

Broadly neutralizing antibodies against Omicron-included SARS-CoV-2 variants induced by vaccination

The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection-and vaccination-induced antibodies,highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies(bnAbs).Here,we developed a panel of bnAbs against Omicron and other variants of concern(VOCs)elicited by vaccination of adenovirus-vectored COVID-19 vaccine(Ad5-nCoV).