Abstract
Nucleotide exchange factor (GrpE), a highly conserved antigen, is rapidly expressed and upregulated when Ureaplasma urealyticum infects a host, which could act as a candidative vaccine if it can induce an anti-U. urealyticum immune reaction. Here, we evaluated the vaccine potential of recombinant GrpE protein adjuvanted by Freund's adjuvant (FA), to protect against U. urealyticum genital tract infection in a mouse model. After booster immunization in mice with FA, the GrpE can induced both humoral and cellular immune response after intramuscular injection into BALB/c mice. A strong humoral immune response was detected in the GrpE-immunized mice characterized by production of high titers of antigen-specific serum IgG (IgG1, IgG2a, and IgG3) antibodies. At the same time, the GrpE also induced a Th1-biased cytokine spectrum with high levels of IFN-γ and TNF-α after re-stimulation with immunogen GrpE in vitro, suggesting that GrpE could trigger the Th1 response when used for vaccination in the presence of FA. Although GrpE vaccination in the presence of a Th1-type adjuvant-induced had readily detectable Th1 responses, there wasn't increase inflammation in response to the infection. More importantly, the robust immune responses in mice after immunization with GrpE showed a significantly reduced U. urealyticum burden in cervical tissues. Histopathological analysis confirmed that tissues of GrpE-immunized BALB/c mice were protected against the pathological effects of U. urealyticum infection. In conclusion, this study preliminarily reveals GrpE protein as a promising new candidate vaccine for preventing U. urealyticum reproductive tract infection.
Highlights
Ureaplasma urealyticum, one of the smallest self-replicating prokaryotic microorganisms, belongs to the Mollicutes class of bacteria and lacks a cell wall, it evolved from Gram-positive ancestors [1]
The results clearly show that intramuscular injection of recombinant GrpE into BALB/c mice generates a specific antibody response
Our results showed that the recombinant GrpE protein mainly induces Th1 response of higher IgG2a and IgG3 antibodies level, and is as easy to detect as IgG1 antibodies (Figure 2B)
Summary
Ureaplasma urealyticum, one of the smallest self-replicating prokaryotic microorganisms, belongs to the Mollicutes class of bacteria and lacks a cell wall, it evolved from Gram-positive ancestors [1]. U. urealyticum is generally regarded as a low-virulent commensal, which commonly colonizes the adult genitourinary tract in humans [2]. Adults are mainly infected through sexual contact, with the cervix being the main site of colonization in women. Maternalfetal transmission seems to occur frequently, and intra-amniotic U. urealyticum infection may contribute to chorioamnionitis and preterm birth [7, 8]. Chronically asymptomatic infections can be frequent in women and may cause pelvic inflammation and sterility. U. urealyticum infections are often be cured by antibiotics, they can be chronic, persistent, and antibiotic resistant [6, 11, 12]. The availability of a safe and effective vaccine would represent a much-needed and powerful means of protection from U. urealyticum infection and transmission
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