1. Introduction
accines used to prevent and control pathogens include DNA vaccines, subunit vaccines, attenuated live vaccines, as well as vector (carrier) vaccines. Current strategies have focused on developing novel vaccines against infectious diseases; they are based on identifying the immunogenic antigens capable of eliciting the necessary immune response to fight pathogens and their delivery system [7]. The present review study aimed to introduce non-pathogenic, non-invasive, and safe Lactococcus lactis bacteria. Furthermore, we evaluated the advantages and limitations of using recombinant Lactococcus lactis-based vaccines; review studies on oral vaccines based on them; vaccine promotion methods and future prospects, as a promising strategy for vaccine production, and preventing some infectious diseases.
2. Materials and Methods
In this review article, 62 articles related to Lactococcus and its wide applications concerning oral vaccine production were collected from 1998 to 2020. Accordingly, we searched the following databases: Scopus, PubMed, and Google Scholar databases. The keywords used in this study included ”Immunity, Lactococcus lactis, and Mucosal, Vaccine” (Figures 1, 2, 3, 4 & Table 1).   

3. Results
Lactococcus lactis is Generally Recognized As Safe (GRAS) and can be widely used in the food industry. Live recombinant Lactococcus lactis, as a biopharmaceutical, is administered orally as a live vaccine expressing viral and bacterial antigens.
4. Discussion and Conclusion 
Vectors based on recombinant lactococci can be desirable alternatives to attenuated strain vaccines. Furthermore, they can be considered as a food-grade and safe host for producing human products, compared to other manufacturing systems. It also has a high potential for vaccine delivery, especially through mucosal methods for the prevention or treatment of some diseases. Additionally, Lactococcus lactis is among the most suitable cellular plants for the expression and secretion of heterologous proteins. A reason for the widespread use of this bacterium is the rapid secretion of protein in this bacterium and the feasible purification of the protein. Moreover, Lactococcus lactis is an efficient host for producing recombinant proteins for therapeutic purposes [34]. Lactococci, for several main reasons, can induce mucosal immunity (secretory IgA secretion) and systemic immunity, resist acidic gastric conditions, bind to the intestinal epithelium, and enhance the immune response as an adjuvant. Besides, the poor immune response against them, less immunity tolerance to them, also less adverse effects make it an appropriate option of live vectors in immunotherapy and immunoprophylaxis. With these characteristics, LAB-based vectors are a suitable alternative to vaccines for the attenuated strains of pathogenic microorganisms, liposomes, and microparticles [1]. Recombinant lactococcus, as a food-grade safe host for producing the desired product, food, or other human consumption is safer than other production systems. However, using such genetically modified microorganisms requires extensive clinical and controlled studies and the proper evaluation of the performance and safety of such drugs, especially for humans.

Ethical Considerations
Compliance with ethical guidelines
This article was approved by the Ethical Research Committee of Arak University of Medical Sciences with the number 1396/99.

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors. 

Authors' contributions
All authors met the standard criteria for writing based on the recommendations of the International Committee of Publishers of Medical Journals (ICMJE).

Conflicts of interest
The authors stated no conflicts of interest.
 

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