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ABSTRACT
Introduction
The use of biocompatible polymers, from natural or synthetic sources, opened the door for a new era in vaccine research. These polymers offer the possibility to develop nanostructured antigen carriers that can be easily internalized by antigen-presenting cells, due to their nanometric size. Besides, the incorporation of an adjuvant allows increasing and modulating the immune response for both, polymers with or without self-adjuvant properties.
Areas covered
The historical background and the state-of-the-art in the use of polymers as antigen carriers are addressed in the first part of this review. Then, an overview of the immunology of vaccination is provided. Finally, the main advances in the field, based on the prototypes that are licensed or undergoing clinical trials, but also the challenges that limit the translation of many polymer-based nanostructure vaccines with promising preclinical results, are discussed.
Expert opinion
Polymeric nanostructured vaccines have a great potential in modern vaccinology. However, the translation into the market is hampered due to several limitations. Studies on correlates of protection to provide suitable biomarkers, new and better methods of synthesis to produce more reproducible nanovaccines, a deeper knowledge in the immune system and in the physiopathology of the infectious diseases will surely improve and boost the field in the next years.
Article highlights
Subunit vaccines are safer than those containing whole pathogens but less immunogenic. For that reason, nanostructures carrying antigen and immunostimulant molecules, such as pathogen-associated molecular patterns (PAMPs), are a good alternative for the development of efficacious vaccines for both, prophylactic and therapeutic approaches.
Nanostructures, due to their pathogen-like sizes and shapes, are well internalized by antigen-presenting cells (APCs). Intensive research on polymeric nanostructures for antigen delivery to APCs has been conducted in the last decades, as well as, in the development of synthetic polymers with self-adjuvant properties.
Development of new nanoparticulated adjuvants has been a hallmark in modern vaccines. Specifically, oil-in-water nanoemulsions with good immunostimulant properties and the capacity to induce broader immune responses (T helper Th1/Th2) than the conventional aluminum salts have been approved.
Vaccines composed of virus mimetic particles, mainly the virus-like particles (VLPs), have also been successfully licensed; however, other polymeric nanostructured vaccines have not reached the market yet, apart from some limited exceptions. One of the main drawbacks for some polymeric nanostructures to reach the market is the lack of stability and the batch-to-batch reproducibility.
Systematic studies are strongly needed for the identification of correlates of immune protection associated with the nanocarrier physicochemical properties, composition, antigens, and adjuvants selected.
A deeper immunological understanding of some complex infectious diseases like tuberculosis or malaria, and chronic diseases like cancer, is crucial to improve vaccine design and, accordingly, its efficacy.
This box summarizes key points contained in the article.
Declaration of interest
A González-Fernández is co-promotor of the company NanoImmunoTech. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Supplementary material
Supplemental data for this article can been accessed here.