Pattern-recognition receptors sensing ALVAC vector components (PRRs (ALVAC))

Pattern-recognition receptors (PRRs) sensing ALVAC vector components are a specialized group of innate immune sensors that detect the canarypox virus-based ALVAC vector. ALVAC is a highly attenuated, non-replicating poxvirus used as a delivery vehicle in various vaccine candidates, most notably in the RV144 HIV-1 vaccine trial (Rerks-Ngarm et al., 2009). Upon entry into host cells, ALVAC releases viral DNA and generates double-stranded RNA (dsRNA) intermediates, which are detected by cytoplasmic sensors such as cyclic GMP-AMP synthase (cGAS), Absent in Melanoma 2 (AIM2), and the NLRP3 inflammasome (Poli et al., 2013; Poli et al., 2017). The activation of these PRRs triggers downstream signaling pathways, specifically the cGAS-STING axis and inflammasome assembly, leading to the production of Type I interferons (IFN-α/β) and pro-inflammatory cytokines like IL-1β and IL-18. These sensing mechanisms are critical for the immunogenicity of ALVAC-based vaccines, as they provide the necessary danger signals or adjuvant effects required to prime adaptive immune responses. By stimulating these receptors, ALVAC promotes the maturation of dendritic cells and the subsequent activation of T-cells and B-cells. While primarily studied in the context of HIV prevention, ALVAC-sensing PRRs are also relevant in cancer immunotherapy, where the vector is used to deliver tumor-associated antigens. Understanding the specific PRRs involved allows for the rational design of more effective viral vectors and adjuvants that can precisely modulate the innate immune environment to achieve protective immunity.

Other names

ALVAC-sensing PRRsInnate immune sensors of canarypox virusPoxvirus-sensing receptorscGAS-STING and AIM2 sensing of ALVAC

Agonism of innate immune sensors (cGAS, AIM2, TLR3, NLRP3) to induce pro-inflammatory cytokines and Type I interferons, enhancing adaptive immune responses.