Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation

Abstract

Vaccine development has had a huge impact on human health. However, there is a significant need to develop efficacious vaccines for several existing as well as emerging respiratory infectious diseases. Several challenges need to be overcome to develop efficacious vaccines with translational potential. This review focuses on two aspects to overcome some barriers – 1) the development of nanoparticle-based vaccines, and 2) the choice of suitable animal models for respiratory infectious diseases that will allow for translation. Nanoparticle-based vaccines, including subunit vaccines involving synthetic and/or natural polymeric adjuvants and carriers, as well as those based on virus-like particles offer several key advantages to help overcome the barriers to effective vaccine development. These include the ability to deliver combinations of antigens, target the vaccine formulation to specific immune cells, enable cross-protection against divergent strains, act as adjuvants or immunomodulators, allow for sustained release of antigen, enable single dose delivery, and potentially obviate the cold chain. While mouse models have provided several important insights into the mechanisms of infectious diseases, they are often a limiting step in translation of new vaccines to the clinic. An overview of different animal models involved in vaccine research for respiratory infections, with advantages and disadvantages of each model, are discussed. Taken together, advances in nanotechnology, combined with the right animal models for evaluating vaccine efficacy, has the potential to revolutionize vaccine development for respiratory infections.

Mucosal vaccine delivery: Current state and a pediatric perspective

“…Polyanydride-based particles are biodegradable and biocompatible, and have recently been used for mucosal vaccination in addition to their use for vaccination via other parenteral routes [110]. Ulrey et al showed that a single intranasal dose of recombinant protein F1-V encapsulated in polyanydride particles could induce long-lived protective immunity in mice against Yersinia pestis , which can causes pneumonic plague, a severe respiratory disease [111].…”

Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell-mediated immune response in pigs

“…The particulate vaccines trials to advance the potential of nanotechnology based approach demand the evaluation of a candidate vaccines in multiple animal models, including in pig before choosing the right model for translational studies to revolutionize vaccine development against highly demanding respiratory infections like influenza in humans [80]. In mice using a welldefined and highly conserved IAV-derived CTLs peptides encapsulated in PLGA microspheres induction of strong CTLs response and complete protection against a viral challengewas achieved [81].…”

Histological studies on the development of porcine tonsils after birth

“…To observe the development of porcine tonsils, we sampled the tonsils, and observed histological changes of tonsils from birth to sexual maturity. An understanding of porcine tonsillar development may lay the foundation for further studies on the immune mechanism of tonsils and for nasal and oral vaccination (Renukaradhya et al, ).…”

“…However, because of the absence of tonsils in mice, the use of mouse models has limitations for the study of human respiratory disease. Porcine respiratory tracts are more similar to humans than those of mice; therefore, pigs are considered to be an ideal animal model for humans (Renukaradhya, Narasimhan, & Mallapragada, 2015).…”