A Self-Biomineralized Novel Adenovirus Vectored COVID-19 Vaccine for Boosting Immunization of Mice.

A Self-Biomineralized Novel Adenovirus Vectored COVID-19 Vaccine for Boosting Immunization of Mice.
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DOI:
10.1007/s12250-021-00434-3
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发表时间:
2021-10
期刊:
影响因子:
5.5
通讯作者:
Li C
Li C
中科院分区:
医学2区
文献类型:
--
作者:
Luo S;Zhang P;Zou P;Wang C;Liu B;Wu C;Li T;Zhang L;Zhang Y;Li C

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SARS-CoV-2已在全球造成380多万人死亡,几种类型的COVID-19疫苗被紧急批准使用,包括腺病毒载体疫苗。然而,热不稳定性和预先存在的免疫力限制了它的广泛应用。为了克服这些障碍,我们构建了一个自生物矿化腺病毒载体COVID-19疫苗(Sad 23 L-nCoV-S-CaP),在生理条件下,在携带SARS-CoV-2刺突蛋白(S)全长基因的Sad 23 L载体的基础上产生一个磷酸钙矿物外壳(CaP)。检测了该Sad 23 L-nCoV-S-CaP疫苗的结构、热稳定性、免疫原性和避免预先存在的免疫问题的特征。在热稳定性试验中,Sad 23 L-nCoV-S-CaP可在4 °C下储存超过45天,在26 °C下储存超过8天,在37 °C下储存约2天。此外,Sad 23 L-nCoV-S-CaP诱导了更高水平的S特异性抗体和T细胞应答,并且不受预先存在的抗Sad 23 L免疫的影响,表明其可以用作Sad 23 L-nCoV-S引发疫苗的加强免疫。用Sad 23 L-nCoV-S-CaP疫苗加强分别诱导105.01抗S1、104.77抗S2结合抗体、103.04假病毒中和抗体(IC 50)的高滴度和IFN-γ(1466.16 SFC/106细胞)对S肽的稳健T细胞应答。综上所述,COVID-19疫苗Sad 23 L-nCoV-S-CaP的自身生物矿化提高了疫苗效力,可用于预防人类SARS-CoV-2感染的初免-加强方案。在线版本包含补充材料,可通过10.1007/s12250-021-00434-3获得。
SARS-CoV-2 has caused more than 3.8 million deaths worldwide, and several types of COVID-19 vaccines are urgently approved for use, including adenovirus vectored vaccines. However, the thermal instability and pre-existing immunity have limited its wide applications. To circumvent these obstacles, we constructed a self-biomineralized adenovirus vectored COVID-19 vaccine (Sad23L-nCoV-S-CaP) by generating a calcium phosphate mineral exterior (CaP) based on Sad23L vector carrying the full-length gene of SARS-CoV-2 spike protein (S) under physiological condition. This Sad23L-nCoV-S-CaP vaccine was examined for its characteristics of structure, thermostability, immunogenicity and avoiding the problem of preexisting immunity. In thermostability test, Sad23L-nCoV-S-CaP could be stored at 4 °C for over 45 days, 26 °C for more than 8 days and 37 °C for approximately 2 days. Furthermore, Sad23L-nCoV-S-CaP induced higher level of S-specific antibody and T cell responses, and was not affected by the pre-existing anti-Sad23L immunity, suggesting it could be used as boosting immunization on Sad23L-nCoV-S priming vaccination. The boosting with Sad23L-nCoV-S-CaP vaccine induced high titers of 105.01 anti-S1, 104.77 anti-S2 binding antibody, 103.04 pseudovirus neutralizing antibody (IC50), and robust T-cell response of IFN-γ (1466.16 SFCs/106 cells) to S peptides, respectively. In summary, the self-biomineralization of the COVID-19 vaccine Sad23L-nCoV-S-CaP improved vaccine efficacy, which could be used in prime-boost regimen for prevention of SARS-CoV-2 infection in humans. The online version contains supplementary material available at 10.1007/s12250-021-00434-3.
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