The recombinant Lactococcus lactis oral vaccine induces protection against C. difficile spore challenge in a mouse model

Autor: Weiwei Yan, Hua Xiang, Sean P. McDonough, Hongxuan He, Maosheng Yang, Katherine J. Wu, Maira Aparecida S. Moreira, Nengfeng Lin, Shanguang Guo, Yung-Fu Chang
Rok vydání: 2015
Předmět:
Colon
Bacterial Toxins
Genetic Vectors
Clostridium difficile toxin A
Clostridium difficile toxin B
Biology
Microbiology
law.invention
Enterotoxins
Mice
Bacterial Proteins
law
Chlorocebus aethiops
Escherichia coli
Lactococus lactisTcd
medicine
Animals
Colitis
Vero Cells
Spores
Bacterial
Mouth
Vaccines
Synthetic
General Veterinary
General Immunology and Microbiology
Clostridioides difficile
Immunogenicity
Lactococcus lactis
Vaccine trial
Public Health
Environmental and Occupational Health
Clostridium difficile
medicine.disease
biology.organism_classification
Antibodies
Bacterial
Virology
Recombinant Proteins
ATcbB
Mice
Inbred C57BL
Disease Models
Animal
Infectious Diseases
Immunoglobulin G
Bacterial Vaccines
Immunoglobulin A
Secretory
Clostridium Infections
Recombinant DNA
Molecular Medicine
Genetic Engineering
Zdroj: LOCUS Repositório Institucional da UFV
Universidade Federal de Viçosa (UFV)
instacron:UFV
ISSN: 0264-410X
DOI: 10.1016/j.vaccine.2015.02.006
Popis: Clostridium difficile infection (CDI) causes nosocomial antibiotic-associated diarrhea and colitis in the developed world. Two potent cytotoxins, toxin A (TcdA) and toxin B (TcdB) are the virulence factors of this disease and can be a good vaccine candidate against CDI. In the present study, we genetically engineered Lactococcus lactis to express the nontoxic, recombinant fragments derived from TcdA and TcdB C-terminal receptor binding domains (Tcd-AC and Tcd-BC) as an oral vaccine candidate. The immunogenicity of the genetically engineered L. lactis oral vaccine delivery system (animal groups LAC and LBC or the combination of both, LACBC) was compared with the recombinant TcdA and TcdB C-terminal receptor binding domain proteins (animal groups PAC and PBC or the combination of both, PACBC), which were expressed and purified from E. coli. After the C. difficile challenge, the control groups received PBS or engineered L. lactis with empty vector, showed severe diarrhea symptoms and died within 2–3 days. However, both the oral vaccine and recombinant protein vaccine groups had significantly lower mortalities, body weight decreases and histopathologic lesions than the control sham-vaccine groups (p < 0.05) except group LBC which only had a 31% survival rate after the challenge. The data of post infection survival showed that an average of 86% of animals survived in groups PAC and PACBC, 75% of animals survived in group LACBC, and 65% of animals survived in group LAC. All of the vaccinated animals produced higher titers of both IgG and IgA than the control groups (p < 0.05), and the antibodies were able to neutralize the cytopathic effect of toxins in vitro. The results of this study indicate that there is a potential to use L. lactis as a delivery system to develop a cost effective oral vaccine against CDI.
Databáze: OpenAIRE
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