Genetic engineering strategies for construction of multivalent chimeric VLPs vaccines

ABSTRACT

Introduction: Over the past two decades, virus-like particles (VLPs) have been developed as a new generation of vaccines against viral infections. Based on VLPs, chimeric VLPs (chi–VLPs) have been generated through genetic modifications or chemical couplings. For construction of multivalent chi–VLPs vaccines, multiple genetic engineering strategies are continuously being developed. Thus, it is important to provide a summary as reference for researchers in this field.

Areas covered: The representative studies on the genetic engineered multivalent chi–VLPs are summarized and mainly focused on chimeric capsid VLPs and chimeric enveloped VLPs. The advantages and limitations of each strategy are also discussed at last, as well as opinions on platform choice and future directions of eVLPs vaccines.

Expert opinion: The design of multivalent chi–VLPs vaccines needs to meet the following specifications: 1) the incorporated antigens are suggested to display on the exposed surface of chi–VLPs and do not have excessive adverse effects on the stability of chi–VLPs; 2) the chi–VLPs should elicit protective antibodies against the incorporated antigen as well as the source virus of VLPs. However, there is no requirement of retaining the antigenicity of VLPs when using VLPs solely as carriers for antigens display or drug delivery.

KEYWORDS:

• Chimeric virus-like particles
• multivalent vaccines
• construction strategy
• VLPs vaccine
• genetic fusion
• foreign antigens
• capsid
• envelope

Acknowledgement

We would like to thank Xiuyue Chen, Yifan Jiang and Yiwen Qin for assistance with data collection. We are also grateful to prof. Naidong Wang and prof. Aibing Wang for critical reading of the manuscript.

Article Highlights

• To elicit a high-level B cell response, foreign antigens can be displayed on the chi-VLPs by fusion to the surface exposed N/C-ter or loops of Caps or envelope proteins.

• N/C-ter junction can accommodate large peptides and loops insertions prefer short epitopes or motifs.

• For the construction of multivalent chi-VLPs vaccines, incorporated antigens should not have excessive adverse effects on the stability of chi-VLPs and antigenicity of original VLPs.

• Foreign antigens can be anchored on the envelope of chi-eVLPs by adding specific elements of SP, HR, TM/CT, or GPI domains.

• eVLPs also have great potentials in application of vaccines. Since more candidate sites and more flexible structures are advantages for modifications in envelope proteins compared with Caps.

• Future success of eVLPs and chi-eVLPs vaccines may lie in 1) accommodation of cellular membrane consumption and improvement of eVLPs secretion, 2) development of technologies in eVLPs purification and storage, 3) structure analysis and prediction of membrane proteins.

Author Contributions

Xinnuo Lei drafted and wrote the main body of the manuscript, including the revision. Xiong Cai reviewed the manuscript and proposed valuable suggestions. Yi Yang wrote, supervised and revised this manuscript.

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 grants from the Hunan Provincial Natural Science Foundation (grant no. 2018JJ2293 to CX), Hunan Education Department’s Science & Research Project (grant no. 17K069).