A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants.
A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants.
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DOI：
10.1073/pnas.2116147118
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发表时间：
2021-11-02
影响因子：
11.1
通讯作者：
Ploegh HL
中科院分区：
文献类型：
--
作者：
Pishesha N;Harmand TJ;Rothlauf PW;Praest P;Alexander RK;van den Doel R;Liebeskind MJ;Vakaki MA;McCaul N;Wijne C;Verhaar E;Pinney W 3rd;Heston H;Bloyet LM;Pontelli MC;Ilagan MXG;Jan Lebbink R;Buchser WJ;Wiertz EJHJ;Whelan SPJ;Ploegh HL
疫苗仍然是减少SARS-CoV-2传播、发病率和死亡率的最大希望。现有的疫苗需要冷藏和先进的制造能力，使其分配复杂化，特别是在欠发达国家。我们报告了一种基于蛋白质的SARS-CoV-2疫苗，它直接特异性靶向抗原呈递细胞。它由SARS-CoV-2刺突受体结合结构域（SpikeRBD）融合到识别II类主要组织相容性复合物抗原（VHHMHCII）的纳米抗体组成。我们的疫苗在年轻和老年小鼠中均产生了针对SARS-CoV-2及其变体的强大的体液（高滴度结合和中和抗体）和细胞免疫。VHHMHCII-SpikeRBD在室温下稳定至少7天，并且可以冻干而不损失功效，这是出于物流原因的理想属性。由严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）引起的大流行已导致1亿多人感染和数百万人死亡。有效的疫苗仍然是减少SARS-CoV-2传播、发病率和死亡率的最大希望。目前使用的疫苗需要冷藏和先进的制造能力，这使疫苗的分配复杂化，特别是在欠发达国家。我们报告了一种候选SARS-CoV-2疫苗的开发，该疫苗纯粹基于蛋白质并直接靶向抗原呈递细胞。它由SARS-CoV-2刺突受体结合结构域（SpikeRBD）融合到羊驼衍生的纳米抗体组成，该纳米抗体识别II类主要组织相容性复合物抗原（VHHMHCII）。该疫苗增强了针对SARS-CoV-2及其变体的强大的体液和细胞免疫。用两个剂量的VHHMHCII-SpikeRBD免疫的年轻小鼠和老年小鼠均引发高滴度结合和中和抗体。免疫还诱导强细胞免疫，包括强的CD8 T细胞应答。VHHMHCII-SpikeRBD在室温下稳定至少7天，可冻干而不丧失效力。
Vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. Currently available vaccines require cold storage and sophisticated manufacturing capacity, complicating their distribution, especially in less developed countries. We report a protein-based SARS-CoV-2 vaccine that directly and specifically targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (SpikeRBD) fused to a nanobody that recognizes class II major histocompatibility complex antigens (VHHMHCII). Our vaccine elicits robust humoral (high-titer binding and neutralizing antibodies) and cellular immunity against SARS-CoV-2 and its variants in both young and aged mice. VHHMHCII-SpikeRBD is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy, desirable attributes for logistical reasons. The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 100 million infections and millions of deaths. Effective vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. The vaccines in current use require cold storage and sophisticated manufacturing capacity, which complicates their distribution, especially in less developed countries. We report the development of a candidate SARS-CoV-2 vaccine that is purely protein based and directly targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (SpikeRBD) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHHMHCII). This vaccine elicits robust humoral and cellular immunity against SARS-CoV-2 and its variants. Both young and aged mice immunized with two doses of VHHMHCII-SpikeRBD elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHHMHCII-SpikeRBD is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.
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影响因子：
30.3
作者：
Case, James Brett;Rothlauf, Paul W.;Whelan, Sean P. J.
通讯作者：
Whelan, Sean P. J.
DOI：
10.1084/jem.180.3.1159
发表时间：
1994-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Unutmaz D;Pileri P;Abrignani S
通讯作者：
Abrignani S
影响因子：
56.9
作者：
Baum, Alina;Fulton, Benjamin O.;Kyratsous, Christos A.
通讯作者：
Kyratsous, Christos A.
DOI：
10.1007/978-1-0716-0211-9_9
发表时间：
2020-01-01
期刊：
MERS CORONAVIRUS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Algaissi, Abdullah;Hashem, Anwar M.
通讯作者：
Hashem, Anwar M.
DOI：
10.1126/science.abh1282
发表时间：
2021-04-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Reynolds CJ;Pade C;Gibbons JM;Butler DK;Otter AD;Menacho K;Fontana M;Smit A;Sackville-West JE;Cutino-Moguel T;Maini MK;Chain B;Noursadeghi M;UK COVIDsortium Immune Correlates Network;Brooks T;Semper A;Manisty C;Treibel TA;Moon JC;UK COVIDsortium Investigators;Valdes AM;McKnight Á;Altmann DM;Boyton R
通讯作者：
Boyton R