하나영 (Stanford University, 현 충남대학교)

한빛사논문

조회276

Stanford University, 현 충남대학교

CV File 179 kb

Sci. Transl. Med., 2024 Jul 31;16(758):eadn6605 | https://doi.org/10.1002/adhm.202400240 A comparative immunological assessment of multiple clinical-stage adjuvants for the R21 malaria vaccine in nonhuman primates

Prabhu S Arunachalam ^{1 †}, NaYoung Ha ^{1 †}, S Moses Dennison ², Rachel L Spreng ^{2 3}, Kelly E Seaton ², Peng Xiao ⁴, Yupeng Feng ¹, Veronika I Zarnitsyna ⁵, Dmitri Kazmin¹, Mengyun Hu ¹, Jordan M Santagata ¹, Xia Xie ¹, Kenneth Rogers ⁴, Lisa M Shirreff ⁴, Claire Chottin ⁴, Alexandra J Spencer ⁶, Sheetij Dutta ⁷, Katherine Prieto⁸, Jean-Philippe Julien ^{8 9}, Mark Tomai ¹⁰, Christopher B Fox¹¹, Francois Villinger ⁴, Adrian V S Hill ⁶, Georgia D Tomaras ^{2 3}, Bali Pulendran ^{1 12 13 *}

¹Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.

²Center for Human Systems Immunology, Department of Surgery, Duke University, Durham, NC 27701, USA.

³Duke Human Vaccine Institute, Duke University, Durham, NC 27703, USA.

⁴New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.

⁵Department of Microbiology and Immunology, Emory University, Atlanta, GA 30329, USA.

⁶The Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.

⁷Structural Vaccinology Laboratory, Biologics Research and Development Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.

⁸Program in Molecular Medicine, Hospital for Sick Children Research Institute, Toronto, ON M5G 0A4, Canada.

⁹Departments of Biochemistry and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.

¹⁰Solventum, Saint Paul, MN 55144, USA.

¹¹Access to Advanced Health Institute (AAHI), Seattle, WA 98102, USA.

¹²Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA.

¹³Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA.

^†These authors contributed equally
^*Corresponding author: correspondence to Bali Pulendran

Abstract

Authorization of the Matrix-M (MM)–adjuvanted R21 vaccine by three countries and its subsequent endorsement by the World Health Organization for malaria prevention in children are a milestone in the fight against malaria. Yet, our understanding of the innate and adaptive immune responses elicited by this vaccine remains limited. Here, we compared three clinically relevant adjuvants [3M-052 + aluminum hydroxide (Alum) (3M), a TLR7/8 agonist formulated in Alum; GLA-LSQ, a TLR4 agonist formulated in liposomes with QS-21; and MM, the now-approved adjuvant for R21] for their capacity to induce durable immune responses to R21 in macaques. R21 adjuvanted with 3M on a 0, 8, and 23–week schedule elicited anti-circumsporozoite antibody responses comparable in magnitude to the R21/MM vaccine administered using a 0-4-8–week regimen and persisted up to 72 weeks with a half-life of 337 days. A booster dose at 72 weeks induced a recall response similar to the R21/MM vaccination. In contrast, R21/GLA-LSQ immunization induced a lower, short-lived response at the dose used. Consistent with the durable serum antibody responses, MM and 3M induced long-lived plasma cells in the bone marrow and other tissues, including the spleen. Furthermore, whereas 3M stimulated potent and persistent antiviral transcriptional and cytokine signatures after primary and booster immunizations, MM induced enhanced expression of interferon- and TH2-related signatures more highly after the booster vaccination. Collectively, these findings provide a resource on the immune responses of three clinically relevant adjuvants with R21 and highlight the promise of 3M as another adjuvant for malarial vaccines.

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형식Research article
게재일2024년 07월 (BRIC 등록일 2024-08-06)
연구진국외 연구진
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