Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4( )/CD8( ) T cells and humoral responses in macaques
Z Li, M Khanna, SL Grimley, P Ellenberg, CA Gonelli, Wen Shi Lee, TH Amarasena, AD Kelleher, DFJ Purcell, SJ Kent, C Ranasinghe
Scientific Reports | NATURE RESEARCH | Published : 2020
Inducing humoral, cellular and mucosal immunity is likely to improve the effectiveness of HIV-1 vaccine strategies. Here, we tested a vaccine regimen in pigtail macaques using an intranasal (i.n.) recombinant Fowl Pox Virus (FPV)-gag pol env-IL-4R antagonist prime, intramuscular (i.m.) recombinant Modified Vaccinia Ankara Virus (MVA)-gag pol-IL-4R antagonist boost followed by an i.m SOSIP-gp140 boost. The viral vector-expressed IL-4R antagonist transiently inhibited IL-4/IL-13 signalling at the vaccination site. The SOSIP booster not only induced gp140-specific IgG, ADCC (antibody-dependent cellular cytotoxicity) and some neutralisation activity, but also bolstered the HIV-specific cellular ..View full abstract
Awarded by ANU Discovery Translation Fund Grant
Awarded by National Health and Medical Research Council (NHMRC)
The authors would like to thank Dr. David Boyle for providing the original parental rFPV vaccine constructs, and Dr. Ronald Jackson for his assistance with the recombinant HIV vaccine construction. Support staff and Veterinarian at the AAHL facility for their assistance. Drs. Mee Ling Munier and John Zaunders for advice related to the cytotoxic assays. Ms Xiangyu Zhou for her assist with the scatterplot quadrant analysis and R. This work was supported by the ANU Discovery Translation Fund Grant # 230 awarded to CR and the National Health and Medical Research Council (NHMRC) Development Grant APP1136351 awarded to CR, SJK, ADK, DP.