Oral mRNA Vaccines Against Infectious Diseases- A Bacterial Perspective [Invited]

Abstract

The mRNA vaccines from Pfizer/BioNTech and Moderna were granted emergency approval in record time in the history of vaccinology and played an instrumental role in limiting the pandemic caused by SARS-CoV-2. The success of these vaccines resulted from over 3 decades of research from many scientists. However, the development of orally administrable mRNA vaccine development is surprisingly underexplored. Our group specializing in Salmonella-based vaccines explored the possibility of oral mRNA vaccine development. Oral delivery was made possible by the exploitation of the Semliki Forest viral replicon and Salmonella vehicle for transgene amplification and gene delivery, respectively. Herein we highlight the prospect of developing oral replicon-based mRNA vaccines against infectious diseases based on our recent primary studies on SARS-CoV-2. Further, we discuss the potential advantages and limitations of bacterial gene delivery.

Salmonella-mediated oral delivery of multiple-target vaccine constructs with conserved and variable regions of SARS-CoV-2 protect against the Delta and Omicron variants in hamster

“…Further dose optimization of mix vaccine will be useful to acquire a potential broad-spectrum protection. The findings reinforce the exploitation of bacteria-mediated delivery for the development of safe, effective and convenient oral mRNA vaccine against SARS-CoV-2 and also other infectious diseases [ 49 ].…”

“…The plasmid expressing antigens was delivered by Salmonella -based vaccine strain for efficient delivery of antigens to target tissues [ 13 , 14 ]. With the innate ability of Salmonella to invade and proliferate in professional antigen-presenting cells (APCs), it has the advantage to directly deliver the DNA cargo to these cells and subsequently result in induction of cellular and humoral response [ 49 ]. Also, as safety concern is one of the important considerations in vaccine development especially with live-attenuated bacteria, of the vaccine delivery strain JOL2500 used in this study with genotype of Δlon, ΔcpxR, ΔsifA , and Δasd has been proven to have optimal survival in the host without any virulence [ 14 , 50 ].…”

Nanomaterials for mRNA‐based therapeutics: Challenges and opportunities

“…In addition, conventional vaccines are not suitable for cancer vaccine development. In contrast, mRNA vaccines encoded using tumor‐associated antigens (TAAs) can be developed more rapidly with cost‐effective approaches 111–113 …”

Salmonella as a Promising Curative Tool against Cancer

“…Recently, several studies have focused on cancer treatment using the direct delivery of heterogeneous antigens or genes encoding anti-tumor molecules. Bacteria, including Salmonella species, have been significantly attenuated in their virulence in order to rule out a major threat of systemic infection or collateral damage [ 13 , 29 ].…”