Single administration vaccines: delivery challenges, in vivo performance, and translational considerations

ABSTRACT

Introduction

With a limited global supply of vaccines and an increasing vaccine hesitancy, improving vaccination coverage has become a priority. Current vaccination regimes require multiple doses to be administered in a defined schedule where missed doses may lead to incomplete vaccine coverage and failure of immunization programmes. As such, there is an ever-increasing demand to convert multi-dose injectable vaccines into single-dose formats, often called single administration vaccines (SAVs).

Areas covered

This review summarizes recent developments in the field of SAVs, with a focus on pulsatile or controlled-release formulations. It will identify the technical challenges, translational as well as commercial barriers to SAVs development. Furthermore, the progress of SAV formulations for hepatitis B and polio vaccines will be reviewed thoroughly as case studies, with a focus on the development challenges and the preclinical immunogenicity/reactogenicity data.

Expert opinion

Despite the efforts to develop SAVs, few attempts have advanced to Phase-I trials. Considering the SAV development journey and bottlenecks, including commercial barriers from the early stages, may overcome some of the hurdles around the technology. The renewed global focus on vaccines since the COVID-19 pandemic could facilitate development of a new generation of technologies for pandemic preparedness including strategies for SAVs.

KEYWORDS:

• Single administration vaccines
• vaccine controlled release
• vaccine stability
• commercialization
• Hepatitis B vaccine
• multiple dose vaccine
• microsphere formulation
• PLGA

Article highlights

• Multiple dose COVID-19 vaccines are potential candidates of single administration vaccine technology.

• Modifying release to generate a sustained or pulsatile release profile to minimize burst release is one of the major formulation challenges.

• Maintaining stability of sensitive antigens during different stages of preparation, storage, and in vivo environment is a key challenge associated with SAV.

• Promising SAV attempts have not progressed to human clinical trials yet probably because of cost implications on the final product and the translational cost of taking a product from bench to cGMP manufacturing and into Phase I studies.

• The renewed global focus on vaccinations since the COVID-19 pandemic may provide an impetus for SAV commercialization for pandemic preparedness in the future.

Declaration of interest

‘Aston University and Avaxzipen have a relevant vaccine formulation technology under development with potential for commercialization. As the corresponding author, I have disclosed those interests fully to Taylor & Francis, and have in place a collaboration agreement for managing any potential conflicts arising from this arrangement. M Prasanna, MK Howard and P Dulal are employees of AVaxziPen. A Walters is currently an employee and shareholder of AstraZeneca. 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 material discussed in the manuscript apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and Aston University funded Midlands Integrative Biosciences Training Partnership (MIBTP) (BB/T00746X/1).