Lactococcus lactis Expressing Type I Interferon From Atlantic Salmon Enhances the Innate Antiviral Immune Response In Vivo and In Vitro

Abstract

In salmon farming, viruses are responsible for outbreaks that produce significant economic losses for which there is a lack of control tools other than vaccines. Type I interferon has been successfully used for treating some chronic viral infections in humans. However, its application in salmonids depends on the proper design of a vehicle that allows its massive administration, ideally orally. In mammals, administration of recombinant probiotics capable of expressing cytokines has shown local and systemic therapeutic effects. In this work, we evaluate the use of Lactococcus lactis as a type I Interferon expression system in Atlantic salmon, and we analyze its ability to stimulate the antiviral immune response against IPNV, in vivo and in vitro. The interferon expressed in L. lactis, even though it was located mainly in the bacterial cytoplasm, was functional, stimulating Mx and PKR expression in CHSE-214 cells, and reducing the IPNV viral load in SHK-1 cells. In vivo, the oral administration of this L. lactis producer of Interferon I increases Mx and PKR expression, mainly in the spleen, and to a lesser extent, in the head kidney. The oral administration of this strain also reduces the IPNV viral load in Atlantic salmon specimens challenged with this pathogen. Our results show that oral administration of L. lactis producing Interferon I induces systemic effects in Atlantic salmon, allowing to stimulate the antiviral immune response. This probiotic could have effects against a wide variety of viruses that infect Atlantic salmon and also be effective in other salmonids due to the high identity among their type I interferons.

Efficacy and safety of Oral LL‐37 against the Omicron BA.5.1.3 variant of SARS‐COV‐2: A randomized trial

“…The safety of recombinant L. lactis hybrid GMZ2 (NCT00424944) is confirmed as already publicly used as vaccine against rabies 26 . Furthermore, oral administration of L. lactis secreting interferon I induce systemic effects and reduces viral load in Atlantic salmon 27 . Taken together, these results implied that the LBP (genetically unmodified/or modified) might be a new avenue to treat COVID‐19 patients on account to their excellent safety profiles.…”

“…26 Furthermore, oral administration of L. lactis secreting interferon I induce systemic effects and reduces viral load in Atlantic salmon. 27 Taken together, these results implied that the LBP (genetically unmodified/or modified) might be a new avenue to treat COVID-19…”

Recombinant Probiotic Preparations: Current State, Development and Application Prospects

“…Immunization of mice and piglets with the recombinant strain promoted the development of an immune response against both fimbriae. Furthermore, serum antibodies of immunized animals inhibited the adhesion of ETES strains [147].…”

Importance of Probiotics in Fish Aquaculture: Towards the Identification and Design of Novel Probiotics

“…Recombinant probiotics have also been used to express proteins that stimulate the immune response in fish, such as cytokines [ 145 , 146 ] and chemokines [ 147 ], the intestinal barrier [ 148 ], or enzymes that disrupt chemical communication in pathogens [ 149 ]. In the case of the cytokines, L. lactis has been used to deliver Interferon I and II, conferring protection against IPNV and F. psychrophilum , respectively [ 145 , 146 ].…”

“…Recombinant probiotics have also been used to express proteins that stimulate the immune response in fish, such as cytokines [ 145 , 146 ] and chemokines [ 147 ], the intestinal barrier [ 148 ], or enzymes that disrupt chemical communication in pathogens [ 149 ]. In the case of the cytokines, L. lactis has been used to deliver Interferon I and II, conferring protection against IPNV and F. psychrophilum , respectively [ 145 , 146 ]. On the other hand, a strain from the Bacillus genus isolated from the intestinal microbiota of Nile tilapia has been used to express CC-Chemokine, increasing the humoral and cellular immune response in Nile tilapia [ 147 ].…”