Immune cell surface receptors engaged by ChAd155-hIi-HBV and MVA-HBV vectors

The target 'Immune cell surface receptors engaged by ChAd155-hIi-HBV and MVA-HBV vectors' refers to the collective group of host cell surface molecules that interact with the viral vectors used in the GSK3528869A therapeutic vaccine regimen for chronic hepatitis B. These include entry receptors such as the Coxsackievirus and Adenovirus Receptor (CAR) for the ChAd155 vector and various attachment factors, such as heparan sulfate proteoglycans, for the Modified Vaccinia Ankara (MVA) vector [3, 8]. A key feature of this vaccine is the use of the human Invariant chain (hIi, also known as CD74) fused to HBV antigens, which facilitates the targeting of these antigens to the Major Histocompatibility Complex (MHC) class II pathway to enhance CD4+ T-cell activation [5, 11]. Additionally, the vectors engage innate pattern recognition receptors, including Toll-like receptors (TLRs) like TLR9, to stimulate the production of pro-inflammatory cytokines and interferons that act as intrinsic adjuvants [3, 12]. This multi-receptor engagement is designed to break the immune tolerance associated with chronic HBV infection and induce potent, polyfunctional T-cell responses aimed at achieving a functional cure [1, 6].

Other names

Coxsackievirus and adenovirus receptor (CAR)CXADRCD74 (HLA class II antigen-associated invariant chain)Major Histocompatibility Complex class II (MHC-II)Toll-like receptors (TLR2, TLR4, TLR9)Heparan sulfate proteoglycans (HSPGs)Pattern recognition receptors (PRRs)

The vaccine vectors bind to host cell surface receptors (e.g., CAR for ChAd155) to facilitate entry and subsequent expression of HBV antigens. The antigens are fused to the human Invariant chain (CD74) to enhance their presentation via the MHC class II pathway. Innate immune receptors (TLRs) sense the vector components, providing adjuvant signals that promote the activation of HBV-specific T and B cells.