ABSTRACT
Malaria is a major cause of mortality and morbidity globally. Great efforts have been made in the prevention and the elimination of malaria, especially in controlling the malaria vector, the mosquito. Another promising approach would be the development of malaria vaccines. Malaria vaccine studies can be focused on the pre-erythrocytic-stage antigens and the blood-stage antigens, and on the transmission blocking agents targeting the malaria gametocytes. The blood-stage antigens are the leading candidates in malaria vaccine development, as the blood-stage parasites are responsible for causing symptomatic malaria. Human acquired immunity largely targets on blood-stage antigens. This review focuses on one of the most extensively studied blood-stage antigen, the merozoite surface protein-1 (MSP-1), specifically on its evaluation and immunogenicity in rodents and primate models, and its safety and immunogenicity in human clinical trials.
Subject(s)
Malaria VaccinesABSTRACT
Objective To study the protective immune responses induced by recombinant Bifidobacterium (Bb)-TSO45W-4B-TSOL18 vaccine of Taenia solium (T.solium) in domestic pigs challenged with T.solium eggs.Methods Twenty healthy 40 days old domestic pigs were divided into five groups by random number table according to body weight (15 kg):rBb-TSO45W-4B-TSOL18 vaccine group,rBb-TSO45W-4B vaccine group,rBb-TSOL18 vaccine group,blank vector control group and MRS control group.The content of vaccine in each vaccine group was 1 × 1011 CFU.A total of two immunization times was conducted,once every two weeks.Pigs were challenged with T.solium eggs 4 weeks after the last immunization and killed 3 months after infection.The cysticercus was counted and the reduction of the cysticercus was calculated.Blood was collected to separate sera and prepare peripheral blood lymphocytes (PBMC).The levels of IgG,IgG1 and IgG2a in sera were determined by enzyme linked immunosorbent assay (ELISA).The level of PBMC proliferation was tested using methyltetrazolium (MTT) assay.The levels of interleukin (IL)-2,interferon (IFN)-γ,IL-4 and IL-10 in PBMC culture supernatant were detected using ELISA.Results The reduction of cysticercus was 83.09％,71.36％ and 74.85％ in rBb-TSO45W-4B-TSOL18,rBb-TSO45W-4B and rBb-TSOL18 vaccine groups,respectively.The differences of IgG,IgG1,IgG2a levels in sera between groups were statistically significant (F =132.348,106.336,596.091,all P ＜0.05).The levels of IgG and IgG2a in rBb-TSO45W-4B-TSOL18,rBb-TSO45W-4B and rBb-TSOL18 vaccine groups [(366.81 ± 3.84),(334.94 ± 11.65),(333.52 ± 11.09),(87.74 ± 0.95),(84.48 ± 0.80),(84.30 ± 1.09)mg/L] were higher than those of the MRS control group [(245.94 ± 8.81),(62.61 ± 0.84)mg/L,all P ＜0.05].The levels of IgG1 in rBb-TSO45W-4B-TSOL18,rBb-TSO45W-4B and rBb-TSOL18 vaccine groups [(26.55 ± 1.06),(33.24 ± 1.92),(32.60 ± 1.94)mg/L] were lower than those of the MRS control group [(42.78 ± 0.87)mg/L,all P ＜0.05].The differences of IL-2,IFN-γ,IL-4 and IL-10 levels in PBMC original culture supernatant between groups were statistically significant (F =139.522,1 053.102,769.097,962.298,all P ＜0.05).The levels of IL-2 and IFN-γ in rBb-TSO45W-4B-TSOL18,rBb-TSO45W-4B and rBb-TSOL18 vaccine groups [(212.24 ± 3.12),(205.91 ± 3.18),(205.85 ± 4.35),(28.42 ± 0.28),(25.56 ± 0.28),(25.71 ± 0.35)ng/L] were higher than those of the MRS control group [(174.19 ± 2.14),(17.69 ± 0.28)ng/L,all P ＜0.05],while the levels of IL-4 and IL-10 [(40.45 ± 0.36),(41.38 ± 0.70),(41.52 ± 0.19),(71.45 ± 0.83),(73.38 ± 0.70),(74.77 ± 0.41)rig/L] were lower than those of the MRS control group [(52.57 ± 0.29),(94.82 ± 0.45)ng/L,all P ＜0.05].The differences of PBMC proliferation levels between groups were statistically significant (F =56.318,P ＜0.05).The PBMC proliferation levels in rBb-TSO45W-4B-TSOL18,rBb-TSO45W-4B and rBb-TSOL18 vaccine groups (0.543 ± 0.074,0.481 ± 0.028,0.530 ± 0.053) were higher than those of the MRS control group (0.242 ± 0.053,all P ＜0.05).Conclusions Recombinant Bb-TSO45W-4B-TSOL18 vaccine of T.solium could induce certain protection in domestic pigs.Type Th1 immune response may play an important role in induction of protective immunity.