Recombinant adeno-associated virus serotype 9 AAV-RABVG expressing a Rabies Virus G protein confers long-lasting immune responses in mice and non-human primates. Issue 1 (31st December 2022)

• Record Type: Journal Article
• Authors: Shi, Chenjuan; Tian, Li; Zheng, Wenwen; Zhu, Yelei; Sun, Peilu; Liu, Lele; Liu, Wenkai; Song, Yanyan; Xia, Xianzhu; Xue, Xianghong; Zheng, Xuexing
• Is Part Of: Emerging microbes & infections. Volume 11:Issue 1(2022)
• Page Start: 1439
• Page End: 1451
• Publication Date: 2022-12-31
• Subjects: Adeno-associated virus serotype 9 -- rabies virus -- glycoprotein -- vaccine -- neutralizing antibodies; Medical microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.9041
• DOI: 10.1080/22221751.2022.2078226
• Languages: English
• ISSNs: 2222-1751

Abstract

ABSTRACT: Three or four intramuscular doses of the inactivated human rabies virus vaccines are needed for pre- or post-exposure prophylaxis in humans. This procedure has made a great contribution to prevent human rabies deaths, which bring huge economic burdens in developing countries. Herein, a recombinant adeno-associated virus serotype 9, AAV9-RABVG, harbouring a RABV G gene, was generated to serve as a single dose rabies vaccine candidate. The RABV G protein was stably expressed in the 293T cells infected with AAV9-RABVG. A single dose of 2 × 10 11 v.p. of AAV9-RABVG induced robust and long-term positive seroconversions in BALB/c mice with a 100% survival from a lethal RABV challenge. In Cynomolgus Macaques vaccinated with a single dose of 1 × 10 13 v.p. of AAV9-RABVG, the titres of rabies VNAs increased remarkably from 2 weeks after immunity, and maintained over 31.525 IU/ml at 52 weeks. More DCs were activated significantly for efficient antigen presentations of RABV G protein, and more B cells were activated to be responsible for antibody responses. Significantly more RABV G specific IFN-γ-secreting CD4+ and CD8+ T cells, and IL-4-secreting CD4+ T cells were activated, and significantly higher levels of IL-2, IFN-γ, IL-4, and IL-10 were secreted to aid immune responses. Overall, the AAV9-RABVG was a single dose rabies vaccine candidate with great promising by inducing robust, long-term humoral responses and both Th1 and Th2 cell-mediated immune responses in mice and non-human primates.