Use of lentiviral vectors in vaccination

ABSTRACT

Introduction

Lentiviral vectors have emerged as powerful vectors for vaccination, due to their high efficiency to transduce dendritic cells and to induce long-lasting humoral immunity, CD8⁺ T cells, and effective protection in numerous preclinical animal models of infection and oncology.

Areas covered

Here, we reviewed the literature, highlighting the relevance of lentiviral vectors in vaccinology. We recapitulated both their virological and immunological aspects of lentiviral vectors. We compared lentiviral vectors to the gold standard viral vaccine vectors, i.e. adenoviral vectors, and updated the latest results in lentiviral vector-based vaccination in preclinical models.

Expert opinion

Lentiviral vectors are non-replicative, negligibly inflammatory, and not targets of preexisting immunity in human populations. These are major characteristics to consider in vaccine development. The potential of lentiviral vectors to transduce non-dividing cells, including dendritic cells, is determinant in their strong immunogenicity. Notably, lentiviral vectors can be engineered to target antigen expression to specific host cells. The very weak inflammatory properties of these vectors allow their use in mucosal vaccination, with particular interest in infectious diseases that affect the lungs or brain, including COVID-19. Recent results in various preclinical models have reinforced the interest of these vectors in prophylaxis against infectious diseases and in onco-immunotherapy.

KEYWORDS:

• Antigen expression in vivo
• humoral immunity
• lentiviral vectors
• long-lasting immune memory
• non-integrating lentiviral vectors
• transduction
• t-cell immunity
• vaccination

Acknowledgments

The authors are very grateful to Dr. François Anna (Pasteur-TheraVectys Joint Laboratory) for helpful discussions.

Article highlights

• Lentiviral vectors have emerged as a particularly powerful vaccinal platform, as they exhibit a combined capacity to induce both strong and long-lasting T-cell and humoral immunity.

• Lentiviral vectors are not targets of preexisting vector-specific immunity in human populations.

• Non-integrating versions of lentiviral vectors are highly immunogenic and circumvent the potential genotoxicity associated with the use of integrating vectors.

• The exclusion of all structural and functional HIV genes from the lentiviral genome ensures that the resulting vector is replication defective and only expresses the transgene of interest.

• Pseudotyping of lentiviral vectors with the heterologous Vesicular Stomatitis Virus envelope Glycoprotein (VSV-G) confers them with broad tropism for various cell types, including dendritic cells.

• The potential of lentiviral vectors to transduce non-dividing antigen presenting cells is a favorable characteristic for vaccine development.

• Lentiviral vectors can be engineered to transductionally or transcriptionally target antigen expression to specific host tissue/cells.

• Lentiviral vectors are non-cytopathic and very weakly inflammatory and can therefore be used for mucosal vaccination via the nasal route, with a particular interest in infectious diseases that affect the lungs or brain.

• Recent results in preclinical models have reinforced the relevance of these vectors in both prophylactic vaccination and onco-immunotherapy.

Author contributions

All authors substantially contributed to the conception and design of the review article and interpreting the relevant literature, and have been involved in writing the review article or revised it for intellectual content.

Additional information

Funding

This manuscript was funded by TheraVectys and Institut Pasteur.