The potential of adenoviral vaccine vectors with altered antigen presentation capabilities

ABSTRACT

Introduction: Despite their appeal as vaccine vectors, adenoviral vectors are yet unable to induce protective immune responses against some weakly immunogenic antigens. Additionally, the maximum doses of adenovirus-based vaccines are limited by vector-induced toxicity, causing vector elimination and diminished immune responses against the target antigen. In order to increase immune responses to the transgene, while maintaining a moderate vector dose, new technologies for improved transgene presentation have been developed for adenoviral vaccine vectors.

Areas covered: This review provides an overview of different genetic-fusion adjuvants that aim to improve antigen presentation in the context of adenoviral vector-based vaccines. The influence on both T cell and B cell responses are discussed, with a main focus on two technologies: MHC class II-associated invariant chain and virus-like-vaccines.

Expert opinion: Different strategies have been tested to improve adenovirus-based vaccinations with varying degrees of success. The reviewed genetic adjuvants were designed to increase antigen processing and MHC presentation, or promote humoral immune responses with an improved conformational antigen display. While none of the introduced technologies is universally applicable, this review shall give an overview to identify potential improvements for future vaccination approaches.

KEYWORDS:

• Adenoviral vectors
• adjuvants
• invariant chain
• vaccines
• virus-like particles
• virus-like-vaccines
• cancer
• endogenous retroviruses

Article highlights

• Recombinant adenoviruses are potent vaccine vectors, but are still unable to induce sufficient immune responses against some weakly immunogenic antigens.

• Vector-induced toxicity at high doses raises a requirement for strategies to increase transgene immunogenicity.

• Fusing genetic adjuvants to a transgene, encoded by an adenoviral vector, can increase T- and/or B-cell responses against the target protein.

• Genetic-fusion adjuvants tested in adenoviral vectors are for example β2-microglobulin, heat-shock proteins, calreticulin, C4bp oligomerization sequence, herpes simplex virus glycoprotein D and MHC class II-associated invariant chain.

• The MHC class II-associated invariant chain-technology is currently tested in clinical trials and has the highest potential, by increasing both CD8+ and CD4+ T cell responses.

• Displaying target proteins on adenovirus-encoded virus-like particles (VLVs) can help to present the antigens in a more natural conformation, for inducing potent immune responses against HIV or cancer antigens.

Author contributions

All authors took part in the writing and proofreading of the review. LN wrote the discussion and conclusion, created the figures and table. CF wrote the introduction. LN, CF, ACA and PJH were equally involved in writing and correcting the remaining text.

Declaration of interest

L Neukirch is an inventor on a patent application WO/2019/043127 which pertains virus-like-vaccines for use against cancer and hold option rights for shares in the company InProTher ApS that develops immunotherapy based on virus-like-vaccines. P J Holst is an inventor on the patent applications WO2007062656, WO2010057501A1, WO/2018/037045, WO2018172259, and WO/2019/043127 which pertains to the Invariant chain technology, furin modified invariant chain technology and Virus-Like-Vaccines for use against cancer. PJH is further an employee of and shareholder in InProTher ApS that develops immunotherapy based on virus-like-vaccines. C Fougeroux is an inventor on the patent application WO2018172259, which pertains furin site engineered into the Invariant chain adjuvant technology. A C Andersson is an employee of InProTher ApS that develops immunotherapy based on virus-like-vaccines. 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.

Reviewer Disclosures

A reviewer has disclosed that they are a co-founder of and consultant to a company that is using adenoviral vectors to develop vaccines against cancer and infectious diseases. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

The authors received no financial support for the research, authorship, and publication of this article.