Immunogenicity of Recombinant Attenuated Salmonella enterica Serovar Typhimurium Vaccine Strains Carrying a Gene That Encodes Eimeria tenella Antigen SO7

Abstract

Recombinant attenuated Salmonella vaccines against avian coccidiosis were developed to deliver Eimeria species antigens to the lymphoid tissues of chickens via the type 3 secretion system (T3SS) and the type 2 secretion system (T2SS) of Salmonella. For antigen delivery via the T3SS, the Eimeria tenella gene encoding sporozoite antigen SO7 was cloned downstream of the translocation domain of the Salmonella enterica serovar Typhimurium sopE gene in the parental pYA3868 and pYA3870 vectors to generate pYA4156 and pYA4157. Newly constructed T3SS vectors were introduced into host strain 8879 (⌬phoP233 ⌬sptP1033::xylE ⌬asdA16), an attenuated derivative of the highly virulent UK-1 strain. The SopE-SO7 fusion protein was secreted by the T3SS of Salmonella. The vector pYA4184 was constructed for delivery of the SO7 antigen via the T2SS. The SO7 protein was toxic to Salmonella when larger amounts were synthesized; thus, the synthesis of this protein was placed under the control of the lacI repressor gene, whose expression in turn was dependent on the amount of available arabinose in the medium. The pYA4184 vector was introduced into host strain 9242 (⌬phoP233 ⌬asdA16 ⌬araBAD23 ⌬relA198::araC P BAD lacI TT [TT is the T4ipIII transcription terminator]). In addition to SO7, for immunization and challenge studies we used the EAMZ250 antigen of Eimeria acervulina, which was previously shown to confer partial protection against E. acervulina challenge when it was delivered via the T3SS. Immunization of chickens with a combination of the SO7 and EAMZ250 antigens delivered via the T3SS induced superior protection against challenge by E. acervulina. In contrast, chickens immunized with SO7 that was delivered via the T2SS of Salmonella were better protected from challenge by E. tenella.

Coccidiosis: recent advancements in the immunobiology of Eimeria species, preventive measures, and the importance of vaccination as a control tool against these Apicomplexan parasites

“…27,70,71 Some other researchers have been able to use attenuated Salmonella successfully as a vaccine delivery tool. 61,62 Eimeria spp., being intestinal parasites, have a predisposition to the gut mucosa, and therefore, mucosal delivery of antigens is the preferred target for optimum vaccine efficacy.…”

“…Several antigens, both in their native form and as recombinant proteins, have been successfully employed in various studies. 27,[59][60][61][62][63][64][65][66] Their efficacy in terms of stimulating a robust immune response is remarkable, as they are involved in establishing a well-defined host-parasite relationship. Even though recombinant vaccines have not been successful commercially, efforts are being made to decipher hostparasite interactions, leading to much more meaningful approaches for recombinant vaccine development.…”

Live Attenuated Salmonella Vaccines against Mycobacterium tuberculosis with Antigen Delivery via the Type III Secretion System

“…We have reported the advantages of using new-generation recombinant attenuated Salmonella vaccine (RASV) strains that are phenotypically similar to the wild-type strain at the time of oral vaccination as an alternative for vaccination (23,24,52,79). These RASV strains are able to colonize and persist in the lymphoid tissue without causing disease symptoms when carrying heterologous antigens, thereby inducing higher protective mucosal and systemic immune responses against a number of infectious diseases (27,45,47,48,68,74,83). Additionally, several approaches have been employed to improve the ability of Salmonella to survive in the gastrointestinal tract and to reach the lymphoid tissues.…”

“…Attenuated Salmonella enterica has been used both as a homologous vaccine and as a delivery system for recombinant heterologous antigens to induce protective immunity against several infectious diseases and tumor sources in animal models (10,19,24,27,35,48,53,65,68,70). Oral administration of Salmonella allows infection of Peyer's patches via M cells, as well as phagocytosis by dendritic cells sampling the gut mucosa and colonization of the mesenteric lymph nodes, liver, and spleen, generating mucosal, humoral, and cellular immune responses against Salmonella and its heterologous antigens (10,19,24,49,77,81).…”

“…Several groups of investigators have used the SPI-1 T3SS effector protein SopE or SptP fused to viral (simian immunodeficiency virus [SIV] and lymphocytic choriomeningitis virus [LCMV]) or protozoan (Eimeria acervulina and E. tenella) antigens to deliver these antigens to the host cell cytosol (27,48,68). These investigators demonstrated that delivery of antigens by the T3SS stimulated antigen-specific cytotoxic T-cell responses, antigen-specific CD8 ϩ memory T cells, and protection against challenge with viral or Eimeria pathogens (27,48,68).…”