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Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice.
BMC Infect Dis. 2017 01 11; 17(1):59.BI

Abstract

BACKGROUND

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite with a broad host range including most warm-blooded animals, including humans. T. gondii surface antigen 1 (SAG1) is a well-characterized T. gondii antigen. T. gondii expresses five nonmitochondrial rhomboid intramembrane proteases, TgROM1-5. TgROM4 is uniformly distributed on the surface of T. gondii and involved in regulating MIC2, MIC3, MIC6, and AMA1 during T. gondii invasion of host cells. Bioinformatics have predicted ROM4 B-cell and T-cell epitopes. Immunization strategy is also a key factor in determining the effectiveness of the immune response and has gained increasing attention in T. gondii vaccine research. In this study, we used a DNA prime-peptide boost vaccination regimen to assess the protective efficacy of various vaccination strategies using TgROM4.

METHODS

We identified a polypeptide (YALLGALIPYCVEYWKSIPR) using a bioinformatics approach, and immunized mice using a DNA-prime and polypeptide-boost regimen. BALB/c mice were randomly divided into six groups, including three experimental groups (peptide, pROM4 and pROM4/peptide) and three control groups (PBS, pEGFP-C1 and pSAG1). Mice were then immunized intramuscularly four times. After immunization, IgG and cytokine productions were determined using enzyme-linked immunosorbent assays. The survival time of mice was evaluated after challenge with tachyzoites of T. gondii RH strain. Additionally, the number of cysts in the brain was determined after intragastric challenge with cysts of T. gondii PRU strain.

RESULTS

Mice vaccinated with different immunization regimens (peptide, pROM4 and pROM4/peptide) elicited specific humoral and cellular responses, with high levels of IgG, IgG2a, and interferon (IFN)-γ. Moreover, IgG, IgG2a and IFN-γ levels were highest in the pROM4/peptide group. Immunized mice, especially those in the pROM4/peptide group, had prolonged survival times after challenge with tachyzoites and reduced numbers of brain cysts after infection compared with negative controls.

CONCLUSION

A DNA prime-peptide boost regimen based on ROM4 elicited the highest level of humoral and cellular immune responses among immunization regimens, and may be a promising approach to increase the efficacy of DNA immunization.

Authors+Show Affiliations

Department of Parasitology, Shandong University School of Medicine, Jinan, Shandong Province, 250012, People's Republic of China.Department of Pediatrics, Provincial Hospital Affiliated to Shandong University, Shandong University School of Medicine, 250021, Jinan, Shandong Province, People's Republic of China.Department of Parasitology, Shandong University School of Medicine, Jinan, Shandong Province, 250012, People's Republic of China.Qilu Hospital of shandong University, Qingdao, 266035, Shandong Province, People's Republic of China.Department of Ji Nan Children's Hospital, 250022, Jinan, Shandong Province, People's Republic of China.Department of Parasitology, Shandong University School of Medicine, Jinan, Shandong Province, 250012, People's Republic of China.Department of Parasitology, Shandong University School of Medicine, Jinan, Shandong Province, 250012, People's Republic of China.Department of Parasitology, Shandong University School of Medicine, Jinan, Shandong Province, 250012, People's Republic of China.Department of Parasitology, Shandong University School of Medicine, Jinan, Shandong Province, 250012, People's Republic of China.Department of Parasitology, Shandong University School of Medicine, Jinan, Shandong Province, 250012, People's Republic of China.Department of Parasitology, Shandong University School of Medicine, Jinan, Shandong Province, 250012, People's Republic of China. shenyi.he@hotmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28077075

Citation

Han, Yali, et al. "Protection Via a ROM4 DNA Vaccine and Peptide Against Toxoplasma Gondii in BALB/c Mice." BMC Infectious Diseases, vol. 17, no. 1, 2017, p. 59.
Han Y, Zhou A, Lu G, et al. Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice. BMC Infect Dis. 2017;17(1):59.
Han, Y., Zhou, A., Lu, G., Zhao, G., Wang, L., Guo, J., Song, P., Zhou, J., Zhou, H., Cong, H., & He, S. (2017). Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice. BMC Infectious Diseases, 17(1), 59. https://doi.org/10.1186/s12879-016-2104-z
Han Y, et al. Protection Via a ROM4 DNA Vaccine and Peptide Against Toxoplasma Gondii in BALB/c Mice. BMC Infect Dis. 2017 01 11;17(1):59. PubMed PMID: 28077075.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice. AU - Han,Yali, AU - Zhou,Aihua, AU - Lu,Gang, AU - Zhao,Guanghui, AU - Wang,Lin, AU - Guo,Jingjing, AU - Song,Pengxia, AU - Zhou,Jian, AU - Zhou,Huaiyu, AU - Cong,Hua, AU - He,Shenyi, Y1 - 2017/01/11/ PY - 2016/04/09/received PY - 2016/12/10/accepted PY - 2017/1/13/entrez PY - 2017/1/13/pubmed PY - 2017/7/8/medline KW - Bioinformatics KW - Immunization strategy KW - Peptide KW - ROM4 KW - Toxoplasma gondii KW - Vaccine SP - 59 EP - 59 JF - BMC infectious diseases JO - BMC Infect. Dis. VL - 17 IS - 1 N2 - BACKGROUND: Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite with a broad host range including most warm-blooded animals, including humans. T. gondii surface antigen 1 (SAG1) is a well-characterized T. gondii antigen. T. gondii expresses five nonmitochondrial rhomboid intramembrane proteases, TgROM1-5. TgROM4 is uniformly distributed on the surface of T. gondii and involved in regulating MIC2, MIC3, MIC6, and AMA1 during T. gondii invasion of host cells. Bioinformatics have predicted ROM4 B-cell and T-cell epitopes. Immunization strategy is also a key factor in determining the effectiveness of the immune response and has gained increasing attention in T. gondii vaccine research. In this study, we used a DNA prime-peptide boost vaccination regimen to assess the protective efficacy of various vaccination strategies using TgROM4. METHODS: We identified a polypeptide (YALLGALIPYCVEYWKSIPR) using a bioinformatics approach, and immunized mice using a DNA-prime and polypeptide-boost regimen. BALB/c mice were randomly divided into six groups, including three experimental groups (peptide, pROM4 and pROM4/peptide) and three control groups (PBS, pEGFP-C1 and pSAG1). Mice were then immunized intramuscularly four times. After immunization, IgG and cytokine productions were determined using enzyme-linked immunosorbent assays. The survival time of mice was evaluated after challenge with tachyzoites of T. gondii RH strain. Additionally, the number of cysts in the brain was determined after intragastric challenge with cysts of T. gondii PRU strain. RESULTS: Mice vaccinated with different immunization regimens (peptide, pROM4 and pROM4/peptide) elicited specific humoral and cellular responses, with high levels of IgG, IgG2a, and interferon (IFN)-γ. Moreover, IgG, IgG2a and IFN-γ levels were highest in the pROM4/peptide group. Immunized mice, especially those in the pROM4/peptide group, had prolonged survival times after challenge with tachyzoites and reduced numbers of brain cysts after infection compared with negative controls. CONCLUSION: A DNA prime-peptide boost regimen based on ROM4 elicited the highest level of humoral and cellular immune responses among immunization regimens, and may be a promising approach to increase the efficacy of DNA immunization. SN - 1471-2334 UR - https://www.unboundmedicine.com/medline/citation/28077075/Protection_via_a_ROM4_DNA_vaccine_and_peptide_against_Toxoplasma_gondii_in_BALB/c_mice_ L2 - https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-2104-z DB - PRIME DP - Unbound Medicine ER -