Single-cycle adenovirus vectors in the current vaccine landscape

Abstract

Introduction: Traditional inactivated and protein vaccines generate strong antibodies, but struggle to generate T cell responses. Attenuated pathogen vaccines generate both, but risk causing the disease they aim to prevent. Newer gene-based vaccines drive both responses and avoid the risk of infection. While these replication-defective (RD) vaccines work well in small animals, they can be weak in humans because they do not replicate antigen genes like more potent replication-competent (RC) vaccines. RC vaccines generate substantially stronger immune responses, but also risk causing their own infections. To circumvent these problems, we developed single-cycle adenovirus (SC-Ad) vectors that amplify vaccine genes, but that avoid the risk of infection. This review will discuss these vectors and their prospects for use as vaccines.

Areas covered: This review provides a background of different types of vaccines. The benefits of gene-based vaccines and their ability to replicate antigen genes are described. Adenovirus vectors are discussed and compared to other vaccine types. Replication-defective, single-cycle, and replication-competent Ad vaccines are compared.

Expert commentary: The potential utility of these vaccines are discussed when used against infectious diseases and as cancer vaccines. We propose a move away from replication-defective vaccines towards more robust replication-competent or single-cycle vaccines.

Keywords: Vaccines; adenovirus; gene-based vaccines; replicating.

Figure 1:

Effects of Vector Genome Replication on Antigen Gene Amplification and Production of Infectious Progeny Viruses.

Figure 2:. Adenovirus Vaccines.

Schematic diagram showing Ad genes key to relevant vaccine functions. RC-, SC-, and RD-A ds all carry most Ad ORFs (not shown). Helper-dependent Ads (HD-Ads) are deleted for all of these adenovir us ORFs.