A Rift Valley fever mRNA vaccine elicits strong immune responses in mice and rhesus macaques

Ting Bian; Meng Hao; Xiaofan Zhao; Chuanyi Zhao; Gang Luo; Zhendong Zhang; Guangcheng Fu; Lu Yang; Yi Chen; Yudong Wang; Changming Yu; Yilong Yang; Jianmin Li; Wei Chen

doi:10.1038/s41541-023-00763-2

A Rift Valley fever mRNA vaccine elicits strong immune responses in mice and rhesus macaques

NPJ Vaccines. 2023 Oct 27;8(1):164. doi: 10.1038/s41541-023-00763-2.

Authors

Ting Bian^#^{1

2

3}, Meng Hao^#¹, Xiaofan Zhao¹, Chuanyi Zhao¹, Gang Luo⁴, Zhendong Zhang⁴, Guangcheng Fu¹, Lu Yang¹, Yi Chen¹, Yudong Wang¹, Changming Yu¹, Yilong Yang⁵, Jianmin Li^{6

7}, Wei Chen⁸

Affiliations

¹ Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, 100071, China.
² Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture and Rural Affairs, Nanjing, China.
³ Frontier Biotechnology Laboratory, Zhejiang University-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou, China.
⁴ School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, China.
⁵ Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, 100071, China. yyl_pku@126.com.
⁶ Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, 100071, China. lijmqz@126.com.
⁷ Frontier Biotechnology Laboratory, Zhejiang University-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou, China. lijmqz@126.com.
⁸ Laboratory of Vaccine and Antibody Engineering, Beijing Institute of Biotechnology, Beijing, 100071, China. cw0226@foxmail.com.

^# Contributed equally.

Abstract

Rift Valley fever virus (RVFV) is listed as a priority pathogen by the World Health Organization (WHO) because it causes serious and fatal disease in humans, and there are currently no effective countermeasures. Therefore, it is urgent to develop a safe and efficacious vaccine. Here, we developed six nucleotide-modified mRNA vaccines encoding different regions of the Gn and Gc proteins of RVFV encapsulated in lipid nanoparticles, compared their ability to induce immune responses in mice and found that mRNA vaccine encoding the full-length Gn and Gc proteins had the strongest ability to induce cellular and humoral immune responses. IFNAR^(-/-) mice vaccinated with mRNA-GnGc were protected from lethal RVFV challenge. In addition, mRNA-GnGc induced high levels of neutralizing antibodies and cellular responses in rhesus macaques, as well as antigen-specific memory B cells. These data demonstrated that mRNA-GnGc is a potent and promising vaccine candidate for RVFV.