Safety and immunogenicity of a novel psittacine beak and feather disease vaccine and optimisation of a thermostable spray-dried formulation.

Abstract

Beak and feather disease virus (Circovirus parrot) associated Psittacine Beak and Feather Disease (PBFD) continues to pose a threat to wild and captive parrot populations globally, particularly in Australia where it has been listed as a Key Threatening Process to endangered psittacine bird species. A practical and safe vaccine delivery system for immunologically naïve nestling and fledgling birds is crucial for early seroconversion, to provide a fighting chance against high environmental load of wild type infections. Current experimental vaccines rely on recombinant capsid proteins delivered via parenteral routes, which are poorly suited to large-scale deployment and early-life immunisation. Recognising the limitations of injectable vaccines and the need for minimally invasive strategies, this study explores a novel spray-dried subunit vaccine formulation aimed at improving thermostability, shelf-life, and delivery potential for mucosal immunisation, especially in juvenile birds. This study explores a novel spray-dried PBFD vaccine formulation, addressing key issues of thermostability, mucosal delivery, and early-life applicability. Using a Design of Experiment (DoE) approach, the study optimised spray drying parameters to produce protein macroparticles of 3.1-9.5 μm, ideal for phagocytic uptake by antigen presenting cells. The spray-dried vaccine formulation maintained the residual moisture content within suitable range to balance microbial safety and protein stability under thermal stress. This experimental formulation also retained antigenicity over 12 months at room temperature, outperforming shelf life of the recombinant virus-like particles (VLPs) in physiological buffer. Seroconversion trials in- vivo demonstrated strong humoral responses in experimental chicken model, when administered in intramuscular route. In contrast, seroconversion following mucosal administration (oculonasal or cloacal) was not statistically significant nevertheless, the responses detected in individual birds indicate potential for improvement through the incorporation of mucosal adjuvants and refinement of delivery strategies. This study provides proof-of-concept that a spray-dried, VLP-based PBFD vaccine demonstrates strong antigenicity, thermostability, and extended shelf life, with the capacity to elicit a robust antibody response.