ABSTRACT
Rhodococcus equi (R. equi) is a zoonotic opportunistic pathogen that mainly causes fatal lung and extrapulmonary abscesses in foals and immunocompromised individuals. To date, no commercial vaccine against R. equi exists. We previously screened all potential vaccine candidates from the complete genome of R. equi using a reverse vaccinology approach. Five of these candidates, namely ABC transporter substrate-binding protein (ABC transporter), penicillin-binding protein 2 (PBD2), NlpC/P60 family protein (NlpC/P60), esterase family protein (Esterase), and M23 family metallopeptidase (M23) were selected for the evaluation of immunogenicity and immunoprotective effects in BALB/c mice model challenged with R. equi. The results showed that all five vaccine candidate-immunized mice experienced a significant increase in spleen antigen-specific IFN-γ- and TNF-α-positive CD4 + and CD8 + T lymphocytes and generated robust Th1- and Th2-type immune responses and antibody responses. Two weeks after the R. equi challenge, immunization with the five vaccine candidates reduced the bacterial load in the lungs and improved the pathological damage to the lungs and livers compared with those in the control group. NlpC/P60, Esterase, and M23 were more effective than the ABC transporter and PBD2 in inducing protective immunity against R. equi challenge in mice. In addition, these vaccine candidates have the potential to induce T lymphocyte memory immune responses in mice. In summary, these antigens are effective candidates for the development of protective vaccines against R. equi. The R. equi antigen library has been expanded and provides new ideas for the development of multivalent vaccines.
Subject(s)
Actinomycetales Infections , Bacterial Vaccines , Disease Models, Animal , Immunity, Humoral , Mice, Inbred BALB C , Rhodococcus equi , Animals , Rhodococcus equi/immunology , Rhodococcus equi/genetics , Mice , Bacterial Vaccines/immunology , Bacterial Vaccines/administration & dosage , Actinomycetales Infections/prevention & control , Actinomycetales Infections/immunology , Actinomycetales Infections/microbiology , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Immunity, Cellular , Female , Lung/microbiology , Lung/immunology , Lung/pathology , Bacterial Load , Bacterial Proteins/immunology , Bacterial Proteins/genetics , Interferon-gamma/immunology , Interferon-gamma/metabolismABSTRACT
BACKGROUND: Although laparoscopic pancreaticoduodenectomy (LPD) has been accepted worldwide for treating pancreatic ductal adenocarcinoma (PDA), it is a very technical and challenging procedure. Also, it is unclear whether LPD is superior to open pancreaticoduodenectomy (OPD). This study summarized the experience and efficacy of LPD for treating PDA in our medical center. METHODS: This retrospective cohort study included patients with PDA admitted at the Affiliated Hospital of Jiangnan University from October 2019 and January 2021. Patients received either LPD or OPD. Clinical outcomes (operation time, duration of anesthesia, intraoperative hemorrhage), postoperative complications, and short-term outcomes were compared. Cox proportional hazard model and Kaplan-Meier method were used to analyze overall survival (OS) and progression-free survival (PFS). RESULTS: Among the PDA patients, 101 patients underwent surgical treatment, 4 patients converted from LPD to OPD, and 7 of them received conservative treatment. Forty-six patients were cured of LPD, and 1 of them died shortly after the operation. Moreover, 44 patients received OPD, and there were 2 postoperative deaths. There were significant differences in the location of the operation time, duration of anesthesia, postoperative hemorrhage, abdominal infections, and postoperative pneumonia between the two groups (all p < 0.05). Multivariate analysis showed that LPD was an independent factor negatively correlated with the incidence of pneumonia (relative risk (RR) = 0.072, 95%CI: 0.016-0.326, p = 0.001) and abdominal infection (RR = 0.182, 95%CI: 0.047-0.709, p = 0.014). Also, there were no differences in OS (hazard ratio (HR) = 1.46, 95%CI: 0.60-3.53, p = 0.40) and PFS (HR = 1.46, 95%CI: 0.64-3.32, p = 0.37) at 12 months between the two groups. CONCLUSIONS: LPD could be efficacy and feasible for managing selected PDA patients. Also, LPD has a better effect in reducing postoperative pneumonia and abdominal infection compared to OPD.