An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice.,Science Translational Medicine

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An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice.
Science Translational Medicine ( IF 15.8 ) Pub Date : 2022-01-26 , DOI: 10.1126/scitranslmed.abj5305
Etsuro Nanishi _{1,

2} , Francesco Borriello _{1,

2,

3} , Timothy R O'Meara ₁ , Marisa E McGrath ₄ , Yoshine Saito ₁ , Robert E Haupt ₄ , Hyuk-Soo Seo _{5,

6} , Simon D van Haren _{1,

2} , Cecilia B Cavazzoni ₇ , Byron Brook _{1,

2} , Soumik Barman _{1,

2} , Jing Chen ₈ , Joann Diray-Arce _{1,

2} , Simon Doss-Gollin ₁ , Maria De Leon ₁ , Alejandra Prevost-Reilly ₁ , Katherine Chew ₁ , Manisha Menon ₁ , Kijun Song ₅ , Andrew Z Xu ₅ , Timothy M Caradonna ₉ , Jared Feldman ₉ , Blake M Hauser ₉ , Aaron G Schmidt _{9,

10} , Amy C Sherman _{1,

11} , Lindsey R Baden ₁₁ , Robert K Ernst ₁₂ , Carly Dillen ₄ , Stuart M Weston ₄ , Robert M Johnson ₄ , Holly L Hammond ₄ , Romana Mayer ₁₃ , Allen Burke ₁₃ , Maria E Bottazzi _{14,

15} , Peter J Hotez _{14,

15} , Ulrich Strych _{14,

16} , Aiquan Chang ₁₇ , Jingyou Yu ₁₇ , Peter T Sage ₇ , Dan H Barouch ₁₇ , Sirano Dhe-Paganon _{5,

6} , Ivan Zanoni _{2,

3} , Al Ozonoff _{1,

2} , Matthew B Frieman ₄ , Ofer Levy _{1,

2,

18} , David J Dowling _{1,

2}

Affiliation

Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA 02115, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA.
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Research Computing Group, Boston Children's Hospital, Boston, MA 02115, USA.
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201, USA.
Department of Pathology, University of Maryland Medical Center, Baltimore, MD 21201, USA.
Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine, Houston, TX 77030, USA.
National School of Tropical Medicine and Departments of Pediatrics and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
National School of Tropical Medicine and Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

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.

中文翻译：

氢氧化铝：CpG 佐剂可增强 SARS-CoV-2 受体结合域疫苗对老年小鼠的保护作用。

为了结束 COVID-19 大流行，仍然迫切需要在全球范围内部署能够为多个年龄段提供保护的疫苗，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，但仍需要更多实用且可扩展的 SARS-CoV-2 疫苗来满足全球需求。用适当的佐剂配制的蛋白质亚单位疫苗代表了解决这一迫切需求的一种方法。受体结合域 (RBD) 是 SARS-CoV-2 中和抗体的关键靶点，但免疫原性较差。因此，我们比较了单独的模式识别受体 (PRR) 激动剂或与氢氧化铝 (AH) 配制的模式识别受体 (PRR) 激动剂，并将它们与 AS01B 和 AS03 类乳剂佐剂进行基准测试，以确定它们在年轻和老年小鼠中增强 RBD 免疫原性的潜力。我们发现，相对于单独的 AH，AH 和 CpG 佐剂制剂 (AH:CpG) 在两个年龄组中产生的抗 RBD 中和抗体滴度增加了 80 倍，并保护老年小鼠免受 SARS-CoV-2 攻击。 AH:CpG 佐剂的 RBD 疫苗可引发针对野生型 SARS-CoV-2 和 B.1.351（β）变体的中和抗体，其血清浓度与获得许可的 Pfizer-BioNTech BNT162b2 mRNA 疫苗诱导的血清浓度相当。 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，并增强年轻和老年小鼠的人类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 作为一种负担得起的疫苗，可能对多个年龄组有效。

更新日期：2021-11-16

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