Preclinical developments in the delivery of protein antigens for vaccination

ABSTRACT

Introduction

Vaccine technology has constantly advanced since its origin. One of these advancements is where purified parts of a pathogen are used rather than the whole pathogen. Subunit vaccines have no chance of causing disease; however, alone these antigens are often poorly immunogenic. Therefore, they can be paired with immune stimulating adjuvants. Further, subunits can be combined with delivery strategies such as nano/microparticles to enrich their delivery to organs and cells of interest as well as protect them from in vivo degradation. Here, we seek to highlight some of the more promising delivery strategies for protein antigens.

Areas covered

We present a brief description of the different types of vaccines, clinically relevant examples, and their disadvantages when compared to subunit vaccines. Also, specific preclinical examples of delivery strategies for protein antigens.

Expert opinion

Subunit vaccines provide optimal safety given that they have no risk of causing disease; however, they are often not immunogenic enough on their own to provide protection. Advanced delivery systems are a promising avenue to increase the immunogenicity of subunit vaccines, but scalability and stability can be improved. Further, more research is warranted on systems that promote a mucosal immune response to provide better protection against infection.

KEYWORDS:

• Vaccine
• nano/microparticle
• infectious disease

Article highlights

• The main types of vaccines include live-attenuated, inactivated, and subunit.

• Vaccines can either be delivered by systemic or mucosal routes which will in turn affect the generation of mucosal antibodies.

• Adjuvants are often included in vaccine formulations to increase immunogenicity. Many adjuvants mimic PAMPs to activate the immune system.

• Subunit vaccines are not immunogenic enough on their own and require delivery strategies and adjuvants to improve efficacy.

• Current preclinical delivery strategies for subunit vaccines include lipid-based delivery systems, polymeric nano/microparticles, inorganic nanoparticles, cell-based delivery methods, protein nanoparticles, and microneedles.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by NIH NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) Contract #75N93019C00052 (PI: Ross) and NIH R01AI147497 (PI: Ainslie).