An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice.
An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice.
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DOI：
10.1126/scitranslmed.abj5305
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发表时间：
2022-01-26
影响因子：
17.1
通讯作者：
中科院分区：
文献类型：
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作者：
为结束COVID-19大流行，仍迫切需要在全球部署可为多个年龄组提供保护的疫苗，特别是在低收入和中等收入国家。尽管基于mRNA和腺病毒载体技术的SARS-CoV-2疫苗已迅速开发出来，但还需要额外实用且可扩展的SARS-CoV-2疫苗才能满足全球需求。用适当佐剂配制的蛋白亚单位疫苗代表了解决这一迫切需求的方法。受体结合结构域（RBD）是SARS-CoV-2中和抗体的关键靶点，但免疫原性差。因此，我们比较了模式识别受体（PRR）激动剂单独或与氢氧化铝（AH）一起配制，并将其与AS 01 B和AS 03样乳剂佐剂进行基准测试，以确定其在年轻和老年小鼠中增强RBD免疫原性的潜力。我们发现AH和CpG佐剂制剂（AH：CpG）在两个年龄组中产生的抗RBD中和抗体滴度相对于单独AH增加80倍，并且保护老年小鼠免受SARS-CoV-2攻击。AH：CpG佐剂RBD疫苗在血清浓度与许可的Pfizer-BioNTech BNT 162 b2 mRNA疫苗诱导的血清浓度相当的情况下，引发针对野生型SARS-CoV-2和B.1.351（β）变体的中和抗体。AH：CpG在年轻成年小鼠和老年小鼠的引流淋巴结中诱导相似的细胞因子和趋化因子基因富集模式，并增强年轻和老年人的人单核细胞中细胞因子和趋化因子的产生。这些数据支持进一步开发AH：CpG佐剂RBD作为可负担得起的疫苗，其可在多个年龄组中有效。一种氢氧化铝：CpG佐剂可提高SARS-CoV-2 RBD在老年小鼠中的免疫原性，并激活从老年人中分离的白细胞。
Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic, especially in low- and middle-income countries. Although vaccines against SARS-CoV-2 based on mRNA and adenoviral-vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are required to meet global demand. Protein subunit vaccines formulated with appropriate adjuvants represent an approach to address this urgent need. The receptor-binding domain (RBD) is a key target of SARS-CoV-2 neutralizing antibodies but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists alone or formulated with aluminum hydroxide (AH) and benchmarked them against AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that an AH and CpG adjuvant formulation (AH:CpG) produced an 80-fold increase in anti-RBD neutralizing antibody titers in both age groups relative to AH alone and protected aged mice from the SARS-CoV-2 challenge. The AH:CpG-adjuvanted RBD vaccine elicited neutralizing antibodies against both wild-type SARS-CoV-2 and the B.1.351 (beta) variant at serum concentrations comparable to those induced by the licensed Pfizer-BioNTech BNT162b2 mRNA vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and enhanced cytokine and chemokine production in human mononuclear cells of younger and older adults. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups. An aluminum hydroxide:CpG adjuvant improves SARS-CoV-2 RBD immunogenicity in aged mice and activates leukocytes isolated from older humans.
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DOI：
10.1073/pnas.2106845118
发表时间：
2021-09-21
影响因子：
11.1
作者：
Dalvie NC;Rodriguez-Aponte SA;Hartwell BL;Tostanoski LH;Biedermann AM;Crowell LE;Kaur K;Kumru OS;Carter L;Yu J;Chang A;McMahan K;Courant T;Lebas C;Lemnios AA;Rodrigues KA;Silva M;Johnston RS;Naranjo CA;Tracey MK;Brady JR;Whittaker CA;Yun D;Brunette N;Wang JY;Walkey C;Fiala B;Kar S;Porto M;Lok M;Andersen H;Lewis MG;Love KR;Camp DL;Silverman JM;Kleanthous H;Joshi SB;Volkin DB;Dubois PM;Collin N;King NP;Barouch DH;Irvine DJ;Love JC
通讯作者：
Love JC
影响因子：
16.6
作者：
Bates TA;Leier HC;Lyski ZL;McBride SK;Coulter FJ;Weinstein JB;Goodman JR;Lu Z;Siegel SAR;Sullivan P;Strnad M;Brunton AE;Lee DX;Adey AC;Bimber BN;O'Roak BJ;Curlin ME;Messer WB;Tafesse FG
通讯作者：
Tafesse FG
影响因子：
8
作者：
Dowling, David J.;van Haren, Simon D.;Levy, Ofer
通讯作者：
Levy, Ofer
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
影响因子：
5.5
作者：
Chen WH;Tao X;Agrawal AS;Algaissi A;Peng BH;Pollet J;Strych U;Bottazzi ME;Hotez PJ;Lustigman S;Du L;Jiang S;Tseng CK
通讯作者：
Tseng CK