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

Background The development of an influenza vaccine for poultry that provides broadly protective immunity against influenza H5Nx viruses is a challenging goal. Results Lactococcus lactis (L. lactis)/pNZ8149-HA1-M2 expressing hemagglutinin-1 (HA1) of A/chicken/Vietnam/NCVD-15A59/2015 (H5N6) and the conserved M2 gene of A/Vietnam/1203/2004 (H5N1) was generated. L. lactis/pNZ8149-HA1-M2 could induce significant humoral, mucosal and cell-mediated immune responses, as well as neutralization antibodies. Importantly, L. lactis/pNZ8149-HA1-M2 could prevent disease symptoms without significant weight loss and confer protective immunity in a chicken model against lethal challenge with divergent influenza H5Nx viruses, including H5N6 and H5N1. Conclusions L. lactis/pNZ8149-HA1-M2 can serve as a promising vaccine candidate in poultry industry for providing protection against H5Nx virus infection in the field application.

Orally Fed Recombinant Lactococcus lactis Displaying Surface Anti-Fimbrial Nanobodies Protects Piglets against Escherichia coli Causing Post-Weaning Diarrhea

Post-weaning diarrhea (PWD) and edema disease (ED), caused by enterotoxigenic and Shiga toxin producing Escherichia coli (ETEC and STEC) strains, are important diseases of newly weaned piglets worldwide. The objective of this study is to develop a passive immunization strategy to protect piglets against PWD and ED using recombinant Lactococcus lactis added to piglet diet at weaning. The Variable Heavy chain domains of Heavy chain antibodies (VHHs) or Nanobodies (Nbs), directed against the fimbrial adhesins FaeG (F4 fimbriae) and FedF (F18 fimbriae) of E. coli were cloned and expressed on the surface of L. lactis. In vitro, the recombinant L. lactis strains agglutinated and inhibited adhesion of cognate F4 or F18 fimbriae expressing E. coli to pig villous preparation. In vivo, the anti-F4 L. lactis protected weaned piglets against a challenge with an F4-positive ETEC strain. Piglets supplemented with oral anti-F4 L. lactis showed reduced fecal E. coli shedding. We concluded that the surface expressed Nanobodies on L. lactis neutralized the adhesins of targeted E. coli and abrogated gut colonization, the first step in disease pathogenesis. As a proof of concept, we demonstrated the potential of passive immunization with recombinant L. lactis as a viable alternative to antibiotic prophylaxis in preventing piglet-post-weaning diarrhea.

Recombinant Lactococcus, a New Approach to Oral Vaccines

Background and Aim: The genus of Lactococcus lactis belonging to the Lactic Acid Bacteria (LAB) group, is a gram-positive, faculative anaerobic, non-spore-forming, and non-motile bacterium. The present study aimed to introduce LAB, especially non-pathogenic, non-invasive, and safe Lactococcus lactis. Accordingly, we examined the previous studies concerning the advantages, limitations, promotion methods, and future prospects of oral vaccines based on this bacterium. This is because it is a potentially promising strategy for the vaccine production and prevention of some infectious diseases. Methods & Materials: In this review article, 62 studies related to Lactococcus lactis and its application in producing oral vaccines were collected through searching databases, such as PubMed, Google Scholar, Scopus published from 1981 to 2020. Ethical Considerations This article was approved by the Ethical Research Committee of Arak University of Medical Sciences with the number 1396/99. Results: Lactococcus lactis, as a safe microorganism, is widely used in the food industry. Live recombinant Lactococcus lactis as a "biologic drug" is orally administered as one of the live vaccines expressing viral and bacterial antigens. Conclusion: Recombinant Lactococcus-based vector can be suitable substitutes for live attenuated vaccines. Moreover, it can be a safe and food-grade host for manufacturing the desired products of human consumption over other systems. It also presents a high potential for vaccine delivery, especially through mucosal methods to prevent or treat certain diseases.

Recombinant Lactococcus Expressing a Novel Variant of Infectious Bursal Disease Virus VP2 Protein Can Induce Unique Specific Neutralizing Antibodies in Chickens and Provide Complete Protection

Recent reports of infectious bursal disease virus (IBDV) infections in China, Japan, and North America have indicated the presence of variant, and the current conventional IBDV vaccine cannot completely protect against variant IBDV. In this study, we constructed recombinant Lactococcus lactis (r-L. lactis) expressing a novel variant of IBDV VP2 (avVP2) protein along with the Salmonella resistance to complement killing (RCK) protein, and Western blotting analysis confirmed that r-L. lactis successfully expressed avVP2-RCK fusion protein. We immunized chickens with this vaccine and subsequently challenged them with the very virulent IBDV (vvIBDV) and a novel variant wild IBDV (avIBDV) to evaluate the immune effect of the vaccine. The results show that the r-L. lactis-avVP2-RCK-immunized group exhibited a 100% protection rate when challenged with avIBDV and 100% survival rate to vvIBDV. Furthermore, this immunization resulted in the production of unique neutralizing antibodies that cannot be detected by conventional ELISA. These results indicate that r-L. lactis-avVP2-RCK is a promising candidate vaccine against IBDV infections, which can produce unique neutralizing antibodies that cannot be produced by other vaccines and protect against IBDV infection, especially against the variant strain.