Vector Development Timeline for Mucosal Vaccination and Treatment of Disease Using Lactococcus lactis and Design Approaches of Next Generation Food Grade Plasmids

Abstract

Lactococcus lactis has been used historically in fermentation and food preservation processes as it is considered safe for human consumption (GRAS—Generally Recognized As Safe). Nowadays, in addition to its wide use in the food industry, L. lactis has been used as a bioreactor for the production of molecules of medical interest, as well as vectors for DNA delivery. These applications are possible due to the development of promising genetic tools over the past few decades, such as gene expression, protein targeting systems, and vaccine plasmids. Thus, this review presents some of these genetic tools and their evolution, which allow us to envision new biotechnological and therapeutic uses of L. lactis. Constitutive and inductive expression systems will be discussed, many of which have been used successfully for heterologous production of different proteins, tested on animal models. In addition, advances in the construction of new plasmids to be used as potential DNA vaccines, delivered by this microorganism, will also be viewed. Finally, we will focus on the scene of gene expression systems known as “food-grade systems” based on inducing compounds and safe selection markers, which eliminate the need for the use of compounds harmful to humans or animal health and potential future prospects for their applications.

Protective immunity induced by oral vaccination with a recombinant Lactococcus lactis vaccine against H5Nx in chickens

“…Since the safety profile of L. lactis is well established, this organism has significant appeal as a mucosal vaccine delivery vector [ 17 , 18 ]. Various heterologous bacterial and viral antigens have been expressed on L. lactis , and antigen-specific immune responses have been reported [ 19 , 20 ]. Notably, recombinant L. lactis has been engineered for the design and development of influenza vaccines [ 21 – 23 ].…”

An oral vaccine against CVA16 (Coxsackievirus A16) was developed by constructing a recombinant<i> Lactococcus lactis</i>

“…Secondly, the level of protein expressed by lactic acid bacteria is low, implying that it is easy to purify the exogenous proteins. Moreover, lactic acid bacteria-based oral vaccine is administered through gastrointestinal mucosa antigen presentation, and can induce the production of an effective immune response [13].…”

Advanced Strategies for Food-Grade Protein Production: A New E. coli/Lactic Acid Bacteria Shuttle Vector for Improved Cloning and Food-Grade Expression

“…Overall, these properties make such non-spore forming organism a promising cell factory for high-level proteins production and their in vivo delivery for medical uses. For this purpose, several L. lactis constitutive and inducible expression systems have been proposed, the former being preferable for in vivo expression [24,25,26,27,28].…”