A self-assembled graphene oxide adjuvant induces both enhanced humoral and cellular immune responses in influenza vaccine

Shiyi Huang; Yiyang Li; Shuang Zhang; Youming Chen; Wenqiong Su; David J Sanchez; John D H Mai; Xiao Zhi; Hongjun Chen; Xianting Ding

doi:10.1016/j.jconrel.2023.11.047

A self-assembled graphene oxide adjuvant induces both enhanced humoral and cellular immune responses in influenza vaccine

J Control Release. 2024 Jan:365:716-728. doi: 10.1016/j.jconrel.2023.11.047. Epub 2023 Dec 11.

Authors

Shiyi Huang¹, Yiyang Li², Shuang Zhang², Youming Chen², Wenqiong Su², David J Sanchez³, John D H Mai⁴, Xiao Zhi⁵, Hongjun Chen⁶, Xianting Ding⁷

Affiliations

¹ Department of Pathology, Wenling First People's Hospital, Wenling City, Zhejiang Province 317500, China; Institute for Personalized Medicine, School of Biomedical Engineering, State Key laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai 200030, China.
² Institute for Personalized Medicine, School of Biomedical Engineering, State Key laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai 200030, China.
³ Pharmaceutical Sciences Department, College of Pharmacy, Western University of Health Sciences, Pomona 91766, CA, USA.
⁴ Alfred E. Mann Institute for Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.
⁵ Shanghai Institute of Virology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: zhixiao@sjtu.edu.cn.
⁶ Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. Electronic address: vetchj@shvri.ac.cn.
⁷ Department of Pathology, Wenling First People's Hospital, Wenling City, Zhejiang Province 317500, China; Institute for Personalized Medicine, School of Biomedical Engineering, State Key laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address: dingxianting@sjtu.edu.cn.

PMID: 38036004
DOI: 10.1016/j.jconrel.2023.11.047

Abstract

Antiviral vaccine is essential for preventing and controlling virus spreading, along with declining morbidity and mortality. A major challenge in effective vaccination lies in the ability to enhance both the humoral and cellular immune responses by adjuvants. Herein, self-assembled nanoparticles based on graphene oxide quantum dots with components of carnosine, resiquimod and Zn²⁺ ions, namely ZnGC-R, are designed as a new adjuvant for influenza vaccine. With its high capability for antigen-loading, ZnGC-R enhances antigen utilization, improves DC recruitment, and activates antigen-presenting cells. Single cell analysis of lymphocytes after intramuscular vaccination revealed that ZnGC-R generated multifaceted immune responses. ZnGC-R stimulated robust CD4⁺CCR7^loPD-1^hi Tfh and durable CD8⁺CD44^hiCD62L^- T_EM immune responses, and simultaneously promoted the proliferation of CD26⁺ germinal center B cells. Besides, ZnGC-R elicited 2.53-fold higher hemagglutination-inhibiting antibody than commercial-licensed aluminum salt adjuvant. ZnGC-R based vaccine induced 342% stronger IgG antibody responses compared with vaccines with inactivated virus alone, leading to 100% in vivo protection efficacy against the H1N1 influenza virus challenge.

Keywords: Adjuvant; Graphene oxide quantum dots; Influenza; Mass cytometry; Vaccine.

MeSH terms

Adjuvants, Immunologic / pharmacology
Adjuvants, Pharmaceutic / pharmacology
Antibodies, Viral
Graphite*
Humans
Immunity, Cellular
Influenza A Virus, H1N1 Subtype*
Influenza Vaccines*
Orthomyxoviridae Infections* / prevention & control

Substances

Influenza Vaccines
graphene oxide
Adjuvants, Immunologic
Adjuvants, Pharmaceutic
Antibodies, Viral
Graphite