Design and evaluation of the immunogenicity and efficacy of a biomimetic particulate formulation of viral antigens

Abstract

Subunit viral vaccines are typically not as efficient as live attenuated or inactivated vaccines at inducing protective immune responses. This paper describes an alternative ‘biomimetic’ technology; whereby viral antigens were formulated around a polymeric shell in a rationally arranged fashion with a surface glycoprotein coated on to the surface and non-structural antigen and adjuvant encapsulated. We evaluated this model using BVDV E2 and NS3 proteins formulated in poly-(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with polyinosinic:polycytidylic acid (poly(I:C) as an adjuvant (Vaccine-NP). This Vaccine-NP was compared to ovalbumin and poly(I:C) formulated in a similar manner (Control-NP) and a commercial adjuvanted inactivated BVDV vaccine (IAV), all inoculated subcutaneously and boosted prior to BVDV-1 challenge. Significant virus-neutralizing activity, and E2 and NS3 specific antibodies were observed in both Vaccine-NP and IAV groups following the booster immunisation. IFN-γ responses were observed in ex vivo PBMC stimulated with E2 and NS3 proteins in both vaccinated groups. We observed that the protection afforded by the particulate vaccine was comparable to the licenced IAV formulation. In conclusion, the biomimetic particulates showed a promising immunogenicity and efficacy profile that may be improved by virtue of being a customisable mode of delivery.

Bovine Pestivirus Heterogeneity and Its Potential Impact on Vaccination and Diagnosis

“…An assessment of longitudinal responses to all the different BVDV proteins in the course of natural infection has not been conducted. However, E2 and NS3 have been shown to be the immunodominant proteins by assessment of ex vivo T cell responses to peptide pools representing the whole Pestivirus A (BVDV-1) proteome following experimental infection [ 39 ].…”

“…One such approach, DNA vaccination, has been trialled with mixed success and is generally deemed to be effective but comes with challenges such as the optimal route of delivery. The use of recombinant subunit proteins had earlier been deemed insufficient to provide effective protection, not least when focusing on E2 [ 39 , 78 , 79 , 80 , 81 ]. The combination of antigens (e.g., E2 and NS3) in formulations with molecular adjuvants to stimulate antigen-presenting cells [ 58 , 59 ] has been more successful, but requires further refinement.…”

Distinct Immunologic Properties of Soluble Versus Particulate Antigens

“…In this regard vaccines, in which recombinant proteins are displayed as virus-like particles, such as hepatitis B and human papilloma virus have proven clinically safe and highly effective in preventing the corresponding viral infections ( 16 , 17 ). Many additional vaccination approaches using antigen particulation as a platform are currently under investigation ( 18 – 21 ), to mention only a few.…”

Comparative analysis of adaptive immune responses following experimental infections of cattle with bovine viral diarrhoea virus-1 and an Asiatic atypical ruminant pestivirus

“…The cells were incubated at 37°C for 48 h after which cell-free supernatants were harvested after centrifugation and stored at À80°C until analysed. The release of IFN-c in culture supernatants was measured using a bovine IFNc ELISA as previously described [21]. IFN-c, IL-4, IL-10 and MIP-1b were simultaneously quantified using a custom-designed multi-array electrochemiluminescence detection assay (Meso Scale Discovery, Gaithersburg, USA) as described [22].…”