Subviral particle as vaccine and vaccine platform

Abstract

Recombinant subvirual particles retain similar antigenic features of their authentic viral capsids and thus have been applied as nonreplicating subunit vaccines against viral infection and illness. Additionally, the self-assembled, polyvalent subviral particles are excellent platforms to display foreign antigens for immune enhancement for vaccine development. These subviral particle-based vaccines are noninfectious and thus safer than the conventional live attenuated and inactivated vaccines. While several VLP vaccines are available in the markets, numerous others, including dual vaccines against more than one pathogen, are under clinical or preclinical development. This article provides an update of these efforts.

Lessons learned from successful human vaccines: Delineating key epitopes by dissecting the capsid proteins

“…The dominant neutralizing epitopes are identified using a method of antibody cross-blocking of a given mAb versus a clinical serum or serum from an immunized animal. The detection of virus neutralizing activity is usually achieved by PCR-based 6 virus capturing neutralization assay for HEV-specific antibodies or a pseudovirus neutralization model for anti-HPV antibodies 21,22 . Additionally, the neutralizing effect of serum antibodies against a human viral pathogen can be tested by passive immunity of transferring polyclonal antibodies or administration of one or more monoclonal antibody followed by virus challenge in animal models 8 .…”

“…In addition, VLPs are highly ordered macromolecular assemblies of the viral protein(s), presenting virion-like epitopes that can be uptaken by antigen presenting cells. The VLP antigen with regular and repetitive epitopes has been demonstrated to more effectively stimulate the immune response than subunit proteins or peptides with much smaller molecular weights [5][6][7] .…”

Adjuvant formulations for virus-like particle (VLP) based vaccines

“…The main characteristics of VLPs are their resemblance in morphology, biochemical composition and size (20–200 nm) to the originating native virion but they lack viral genetic material and are therefore unable to replicate or cause infection [23]. Indeed, some VLPs are indistinguishable from the original virion when examined by electron microscopy [26].…”

“…As discussed above, VLPs have a bio-particulate structure that is beneficial for APC recognition and uptake as well as BCR crosslinking [23,30,31]. For this reasons VLPs-based vaccine may not necessitate of adjuvants carriers like aluminum salts, which are important for the delivery of subunit vaccines antigens to APC.…”

“…Furthermore, several clinical trials are currently ongoing for VLP vaccines against influenza [20], norovirus [21], and chikungunya virus (CHIK) [22] (https://clinicaltrials.gov/). Although VLP-based vaccines alone have been shown to be more efficacious than subunit vaccines [23], formulation with adjuvants is relevant to optimize their activity and enhance their potency [24]. Indeed, adjuvants are a class of immunomodulatory molecules [25] able to augment vaccine effectiveness and safety by: 1) enhancing immunogenicity and increasing the duration of protection; 2) broadening the induction of the immune response; 3) reducing vaccine dosage and vaccination cost (antigen sparing); 4) accelerating the immune response; 5) stimulating a stronger immunological memory; 6) improving efficacy in weak responder patients such as neonates, the elderly and immunocompromised individuals (Graphical Abstract).…”