Oral Vaccination with Attenuated Salmonella typhimurium-Delivered TsPmy DNA Vaccine Elicits Protective Immunity against Trichinella spiralis in BALB/c Mice

• Published in: PLoS neglected tropical diseases 2016-09, Vol.10 (9), p.e0004952-e0004952
• Main Authors: Wang, Lei, Wang, Xiaohuan, Bi, Kuo, Sun, Ximeng, Yang, Jing, Gu, Yuan, Huang, Jingjing, Zhan, Bin, Zhu, Xinping
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Antibodies, Helminth - blood; Biology and Life Sciences; Cytokines - blood; Female; Genetic Vectors; Health aspects; Immunoglobulin A - blood; Immunoglobulin G - blood; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Parasite vaccines; Receptors, CCR - genetics; Receptors, CCR10 - genetics; Recombinant proteins; Recombinant Proteins - immunology; Research and Analysis Methods; Salmonella typhimurium - genetics; Salmonella typhimurium - immunology; Th1-Th2 Balance; Trichina worm; Trichinella spiralis - isolation & purification; Trichinellosis - immunology; Trichinellosis - prevention & control; Tropomyosin - immunology; Vaccination - methods; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - immunology; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0004952

Our previous studies showed that Trichinella spiralis paramyosin (TsPmy) is an immunomodulatory protein that inhibits complement C1q and C8/C9 to evade host complement attack. Vaccination with recombinant TsPmy protein induced protective immunity against T. spiralis larval challenge. Due to the difficulty in producing TsPmy as a soluble recombinant protein, we prepared a DNA vaccine as an alternative approach in order to elicit a robust immunity against Trichinella infection. The full-length TsPmy coding DNA was cloned into the eukaryotic expression plasmid pVAX1, and the recombinant pVAX1/TsPmy was transformed into attenuated Salmonella typhimurium strain SL7207. Oral vaccination of mice with this attenuated Salmonella-delivered TsPmy DNA vaccine elicited a significant mucosal sIgA response in the intestine and a systemic IgG antibody response with IgG2a as the predominant subclass. Cytokine analysis also showed a significant increase in the Th1 (IFN-γ, IL-2) and Th2 (IL-4, 5, 6, 10) responses in lymphocytes from the spleen and MLNs of immunized mice upon stimulation with TsPmy protein. The expression of the homing receptors CCR9/CCR10 on antibody secreting B cells may be related to the translocation of IgA-secreted B cells to local intestinal mucosa. The mice immunized with Salmonella-delivered TsPmy DNA vaccine produced a significant 44.8% reduction in adult worm and a 46.6% reduction in muscle larvae after challenge with T. spiralis larvae. Our results demonstrated that oral vaccination with TsPmy DNA delivered by live attenuated S. typhimurium elicited a significant local IgA response and a mixed Th1/Th2 immune response that elicited a significant protection against T. spiralis infection in mice.