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- Title
Vaccination with toxofilin DNA in combination with an alum-monophosphoryl lipid A mixed adjuvant induces significant protective immunity against Toxoplasma gondii.
- Authors
Pengxia Song; Shenyi He; Aihua Zhou; Gang Lv; Jingjing Guo; Jian Zhou; Yali Han; Huaiyu Zhou; Zhen Hao; Hua Cong; Song, Pengxia; He, Shenyi; Zhou, Aihua; Lv, Gang; Guo, Jingjing; Zhou, Jian; Han, Yali; Zhou, Huaiyu; Hao, Zhen; Cong, Hua
- Abstract
<bold>Background: </bold>A widely prevalent disease, toxoplasmosis poses serious health threats to both humans and animals; therefore, development of an ideal DNA vaccine against Toxoplasma gondii is needed eagerly. The purpose of the present study is to assess the protective efficacy of a DNA vaccine encoding the T. gondii toxofilin gene (pEGFP-toxofilin). In addition, toxofilin DNA vaccine combined with the individual adjuvants, alum or monophosphoryl lipid A (MPLA), or a mixture of alum-MPLA adjuvant were screened for their ability to enhance antibody responses.<bold>Methods: </bold>Using bioinformatics, we analyzed the gene and amino acid sequences of the toxofilin protein, recognizing and identifying several potential linear B and T helper (Th)-1 cell epitopes. BALB/c mice were immunized three times with either toxofilin DNA vaccine alone or in combination with the adjuvants such as alum, MPLA or an alum-MPLA mixture. The systemic immune response was evaluated by cytokine, the percentage of CD4 (+) and CD8 (+) T cells and specific antibody measurement. Two weeks after the last immunization, protective efficacy was evaluated by challenging intraperitoneally with 1 × 104 tachyzoites of T. gondii or intragastrically with 20 cysts of T. gondii PRU strain.<bold>Results: </bold>All experimentally immunized mice developed strong humoral and cellular immune responses compared with the control groups. Moreover, by comparison with the non-adjuvant toxofilin DNA vaccine group, adding alum adjuvant to toxofilin DNA vaccine resulted in an increase in humoral response and a skewed Th2 response. However, the MPLA adjuvant with toxofilin DNA vaccine induced significantly enhanced humoral and Th1-biased immune responses. Importantly, the co-administration of alum-MPLA adjuvant in combination with the toxofilin DNA vaccine shifted the Th2 immune response to a Th1 response compared with the alum-toxofilin group, and elicited the strongest humoral and Th1 responses among all the groups. At the same time, a longer survival time and less cyst amounts against T. gondii infection were also observed in the alum-MPLA-toxofilin group in comparison with single or no adjuvant groups.<bold>Conclusions: </bold>Toxoplasma gondii toxofilin is a promising vaccine candidate that warrants further development. Co-administration of the alum-MPLA adjuvant mixture with DNA vaccine could effectively enhance immunogenicity and strongly skew the cellular immune response towards a Th1 phenotype.
- Subjects
DNA vaccines; PHOSPHORYL group; IMMUNE response; TOXOPLASMA gondii; TOXOPLASMOSIS; DISEASE prevalence; VACCINATION; ANIMAL experimentation; IMMUNOMODULATORS; CELLULAR immunity; LIPIDS; MICE; MICROFILAMENT proteins; PROTEINS; PROTOZOA; VACCINES; ALUM compounds; ANTIBODY formation; PHARMACODYNAMICS; PREVENTION
- Publication
BMC Infectious Diseases, 2017, Vol 17, p1
- ISSN
1471-2334
- Publication type
journal article
- DOI
10.1186/s12879-016-2147-1