PropertyValue
?:abstract
  • 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 and humoral responses. Specifically, superior sustained systemic and mucosal HIV Gag-specific poly-functional/cytotoxic CD4(+) and CD8(+) T cells were detected with the IL-4R antagonist adjuvanted strategy compared to the unadjuvanted control. In the systemic compartment elevated Granzyme K expression was linked to CD4(+) T cells, whilst Granzyme B/TIA-1 to CD8(+) T cells. In contrast, the cytotoxic marker expression by mucosal CD4(+) and CD8(+) T cells differed according to the mucosal compartment. This vector-based mucosal IL-4R antagonist/SOSIP booster strategy, which promotes cytotoxic mucosal CD4(+) T cells at the first line of defence, and cytotoxic CD4(+) and CD8(+) T cells plus functional antibodies in the blood, may prove valuable in combating mucosal infection with HIV-1 and warrants further investigation.
is ?:annotates of
?:creator
?:doi
?:doi
  • 10.1038/s41598-020-79172-7
?:journal
  • Sci_Rep
?:license
  • cc-by
?:pdf_json_files
  • document_parses/pdf_json/ad6a52831692aecfc9fa7586b89a79141e7038e0.json
?:pmc_json_files
  • document_parses/pmc_json/PMC7744512.xml.json
?:pmcid
?:pmid
?:pmid
  • 33328567.0
?:publication_isRelatedTo_Disease
is ?:relation_isRelatedTo_publication of
?:sha_id
?:source
  • Medline; PMC
?:title
  • Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4(+)/CD8(+) T cells and humoral responses in macaques
?:type
?:year
  • 2020-12-16

Metadata

Anon_0  
expand all