RT Journal Article
SR Electronic
T1 Investigating vaccine uptake dynamics of neutrophils using HIV-1 Envelope glycoprotein trimer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.10.515906
DO 10.1101/2022.11.10.515906
A1 Philip Y.X. Ngo
YR 2022
UL http://biorxiv.org/content/early/2022/11/13/2022.11.10.515906.abstract
AB Rhesus macaques were previously immunized with two distinct subunit vaccine candidates, to monitor antigen trafficking by immune cells infiltrating the site of injection. The first, a formulation based on the HIV-1 envelope glycoprotein (Env) and the other based on the RSV-fusion (F) protein. Neutrophil and monocyte uptake profiles were vastly different between the vaccine candidates despite similar cell infiltration numbers, hinting that antigen characteristics could orchestrate different innate responses. Notably, the Env trimer is significantly more glycosylated than RSV-F.Recapitulating these in vivo observations under reliable in vitro conditions is thus of importance in exploring uptake dynamics and insights into the manipulation of innate responses. The study later demonstrated a complement component, Mannose Binding Lectin (MBL), to be resistant to heat-inactivation and binds Env in a CRDdependent manner. Interestingly, the data suggests a heat-labile component of the serum hinders MBL from binding to Env, which corresponded to a weaker uptake profile. Also, the generation of 3 differentially glycosylated Env variants to study glycan-mediated uptake by neutrophils derived contrary observations. In all, modulation of MBL interactions could potentially target specific innate immune cells, particularly neutrophils, and the later development of adaptive immune responses after immunization.Competing Interest StatementThe authors have declared no competing interest.AIDSAcquired Immune Deficiency SyndromeAFAlexa FlourCDcluster of differentiationDCdendritic celdLNsDraining Lymph NodesELISAEnzyme-Linked Immunosorbent AssayFCSfetal calf serumFSC-A/Hforward scatter area/heightFcRFragment crystallisable receptorGCgerminal centergpglycoproteinHBSSHank’s balanced salt solutionHIV-1human immunodeficiency virus 1HLA-DRhuman leukocyte antigen – DR isotypeHPLCHigh performance Liquid Chromatographyi.d.Intradermali.m.IntramuscularIgimmunoglobulinMHC-IImajor histocompatibility complex IMWMolecular WeightNHPnon-human primatePBSphosphate buffered salinePMNspolymorphonuclear neutrophilsRMRhesus macaques (Macaca mulatta)ROSreactive oxygen speciesRPMrounds per minuteRTroom temperatureRSVrespiratory syncytial virusSSC-Asideward scatter area