Salmonella typhimurium deletion mutants lacking adenylate cyclase and cyclic AMP receptor protein are avirulent and immunogenic

Curtiss, rd R; Sm, Kelly

doi:10.1128/iai.55.12.3035-3043.1987

Cited by 410 publications

(147 citation statements)

References 61 publications

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“…Attenuated adenoviruses exist in other species which might also be developed for live rDNA vectors permitting expression of the coronavirus gene inserts in the intestine. Similarly, attenuated strains of Salmonella are attractive as potential live vectors for enteric viruses such as coronaviruses because they have the potential to target the expressed proteins directly to lymphoid tissues of the gut (Clements et al, 1986; Curtiss and Kelly, 1987). Although only in the early stages of development, such live rDNA vectors may play a key role in the generation of future coronavirus vaccines.…”

Section: New Strategies For Coronavirus Vaccinesmentioning

confidence: 99%

Coronavirus immunogens

Saif

1993

Veterinary Microbiology

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Coronaviruses (CV) infect a variety of livestock, poultry and companion animals. They belong to at least five antigenic groups. CV cause localized infections of the respiratory and/or intestinal tracts, with the exception of feline infectious peritonitis virus (FIPV) and hemagglutinating encephalomyelitis (HEV) which cause systemic infections. The enteropathogenic CV infect the villous enterocytes resulting in villous atrophy leading to malabsorptive diarrhea. Several CV (bovine CV-BCV, porcine respiratory CV-PRCV, infectious bronchitis virus-IBV) cause respiratory disease. Current evidence indicates that protection against enteric and respiratory CV infections is mediated by passive or active immunity at the primary site of CV replication. Maternal vaccination approaches to induce passive immunity include the use of inactivated and modified live viral vaccines. Modified live viruses and a Ts mutant CV (FIPV) are also used as oral or intranasal vaccines to induce active mucosal immunity. The success of these vaccines in the field is often compromised by a number of potential problems. Coronaviruses are spherical, enveloped viruses, ranging from 80-160 nm in diameter and containing a positive-stranded RNA genome. They possess prominent surface spikes and some species display a fringe of smaller surface projections believed to be the hemagglutinin (HE). Coronaviruses possess 3 to 4 structural proteins: the spike (S) glycoprotein (150-200 kDa), the integral membrane glycoprotein (M; 20-30 kDa) and the nucleocapsid phosphoprotein (N; 43-50 kDa). A subset of CV (BCV, HEV, turkey CV) possess a third glycoprotein on the virion surface, the HE (60-65 kDa). These proteins can be quantitated using pooled monoclonal antibodies (mAb) to distinct epitopes of each protein in ELISA. Most research has focused on the S protein as a candidate antigen for CV vaccines since it induces virus neutralizing (VN) antibodies. However the HE protein stimulates the production of VN and HE inhibiting antibodies and the M protein induces antibodies that neutralize virus in the presence of complement. Attempts to correlate in vitro VN antibody activity with in vivo protection have shown that the passive transfer of VN mAb to the S or HE protein conferred passive protection against CV challenge in some studies, but not others. Additional research has implicated a possible role for other CV proteins in immunity. Studies of mAb to the M protein of transmissible gastroenteritis (TGEV) have provided evidence for a direct role of the M protein in the induction of alpha IFN by porcine blood leukocytes. The potential significance of this phenomenon to immunity to TGEV is unclear.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: New Strategies For Coronavirus Vaccinesmentioning

confidence: 99%

Coronavirus immunogens

Saif

1993

Veterinary Microbiology

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“…A variety of attenuated Salmonella strains have been generated in laboratories worldwide (Bacon et al, 1950;Bacon et al, 1951;Germanier and Furer, 1971;Hoiseth and Stocker, 1981). S. typhimurium Acya Acrp mutants, which are deficient in the synthesis of adenylate cyclase and the cyclic AMP (CAMP) receptor protein (CRP), are both avirulent and immunogenic in orally immunized mice, while retaining their ability to colonize and persist in the GALT (Curtiss III and Kelly, 1987). Several heterologous genes from different pathogens have been expressed in S. typhimurium A cya A crp.…”

Section: Introductionmentioning

confidence: 99%

Characterization of transmissible gastroenteritis coronavirus S protein expression products in avirulent S. typhimurium Δcya Δcrp: persistence, stability and immune response in swine

Smerdou

Urniza²,

Iii

et al. 1996

Veterinary Microbiology

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The spike protein from transmissible gastroenteritis virus (TGEV) was expressed in attenuated S. typhimurium delta cya delta crp delta asd chi 3987. Three partially overlapping fragments of TGEV S gene, encoding the amino-terminal, intermediate, and carboxy-terminal end of the protein, as well as the full length gene were inserted into the asd+ plasmid pYA292 to generate recombinant plasmids pYATS-1, pYATS-2, pYATS-3, and pYATS-4, respectively, which were transformed into S. typhimurium chi 3987. Recombinant S. typhimurium chi 3987 (pYATS-1) and chi 3987 (pYATS-4) expressing constitutively a 53 kDa amino-terminal fragment of the S protein and the full length protein (144 kDa), respectively, showed high stability. After 50 generations in vitro 60% and 20% of the bacteria transformed with pYATS-1 and pYATS-4, respectively, expressed the S-protein antigen. Since S. typhimurium chi 3987 (pYATS-1) showed a better level of expression and stability in vitro, this recombinant strain was selected as a potential bivalent vector to induce both immunity to Salmonella and TGEV in swine. In order to study colonization of swine tissues by S. typhimurium delta cya delta crp, a gene conferring resistance to rifampicin was cloned into the chromosome of S. typhimurium chi 3987, generating chi 4509 strain. Both S. typhimurium chi 4509 (pYA292) and chi 4509 (pYATS-1) colonized the ileum of orally inoculated swine with clearance of bacteria between days 10-20 post-infection. The expression of the amino-terminal fragment of the S protein diminished the ability of S. typhimurium chi 4509 (pYATS-1) to colonize deep tissues. The recombinant strain S. typhimurium chi 3987 (pYATS-1) induced TGEV specific antibodies in both serum and saliva of orally inoculated swine.

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“…They were mainly concerned with survival/persistence of the thyA vaccine strain after excretion, such that thymine-less death under these conditions would be sufficient. This is interesting, since thyA mutants of S. Typhimurium are not attenuated (Curtiss and Kelly, 1987). Of course, L. lactis does not need additional attenuation.…”

Section: Biological Containment Features Of Recombinant Attenuated Bamentioning

confidence: 99%

Antigen Delivery System II

Curtiss

2015

Mucosal Immunology

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Salmonella typhimurium deletion mutants lacking adenylate cyclase and cyclic AMP receptor protein are avirulent and immunogenic

Cited by 410 publications

References 61 publications

Coronavirus immunogens

Coronavirus immunogens

Characterization of transmissible gastroenteritis coronavirus S protein expression products in avirulent S. typhimurium Δcya Δcrp: persistence, stability and immune response in swine

Antigen Delivery System II

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