Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease.

Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirusx2206;VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD.

[Highly active antiretroviral therapy on liver function in HIV-positive children with HBV/HCV co-infection].

OBJECTIVE: To assess changes of liver function in HIV-positive children with/without HBV/ HCV co-infection after 1 year of highly active antiretroviral therapy (HARRT). METHODS: Seventy-eight pediatric AIDS patients with HBV/HCV co-infection,19 pediatric AIDS patients with HBV co-infection and 44 pediatric AIDS patients without HBV/HCV co-infection who received HAART at least for 1 year were enrolled. HIV-1 viral load was quantitatively detected using a standardized reverse transcriptase-polymerase chain reaction assay, and blood cells were determined by three-color flow cytometry. Anti-HCV antibody and HBsAg was detected using an enzyme-linked immunosorbent technique, and ALT, AST and TBIL were detected by automatic biochemical analyzer. RESULTS: After 1 year-HAART, the viral load was decreased to the lowest limit of detection in 90.34% patients (t=2.61, P<0.01), and CD4+ T cell counts were increased from 170.187±132.405/ µl to 796.014±158.491/ µl (t=3.17, P<0.01). The levels of ALT and AST were elevated (t=2.02, P<0.05), while the ALT and AST levels in patients receiving nevirapine (NVP) based HAART increased from 18.28±13.74 U/L and 24.23±8.09 U/L to 55.35±22.40 U/L and 69.97±26.72 U/L, respectively(t=3.80,t=4.11;Ps<0.01). The increment of ALT and AST in NVP based HAART were significantly higher than that in the efavirenz based HAART (ALT:46.28±13.35 U/L vs 37.70±15.25 U/L and AST:19.53±7.23 U/L vs 1.25±0.21 U/L, respectively; t=4.53, t=5.79; Ps<0.01), particularly in patients co-infected with HIV/HBV/HCV (ALT:54.32±22.85 U/L vs 16.89±14.42 U/L and AST:41.71±19.26 U/L vs -3.44±15.59 U/L, respectively; t=3.42, t=2.98, Ps<0.01). CONCLUSION: HARRT can repress HIV-1 replication effectively, but it also cause the damage of liver function, especially in patients with HBV and/or HCV co-infection.

[Expression of CD38 and HLA-DR on CD8+ T cells in pediatric AIDS patients receiving highly active antiretroviral therapy (HAART)].

OBJECTIVE: To study the expression of CD38 and HLA-DR on CD8(+) T cells in pediatric AIDS patients receiving highly active antiretroviral therapy (HAART) and the relationship of immune activation and disease progression. METHODS: A cross-section study of 194 pediatric AIDS patients receiving HAART was carried out and 52 age-matched healthy children were recruited as control. The percentage of CD4(+), CD8(+), CD8(+)/CD38(+) and CD8(+)/HLA-DR(+) T cells was tested using flow cytometry, and HIV-RNA in plasma was detected by quantitative RT-PCR. RESULTS: One hundred and ninety-four pediatric AIDS patients were divided into two groups according to the viral load: 59 patients with VL ≥ 400 copies/ml and 135 patients with VL < 400 copies/ml. The percentage of CD8(+)/CD38(+) and CD8(+)/HLA-DR(+) T cells of patients with VL ≥ 400 copies/ml was significantly higher than that of patients with VL < 400 copies/ml (P < 0.05). Of patients with VL < 400 copies/ml, the percentage of CD8(+)/CD38(+) T cells was nearly normal, and the percentage of CD8(+)/HLA-DR(+) T cells was higher than normal level (P < 0.05). There was a positive correlation between percentage of CD8(+)/CD38(+) and of CD8(+)/HLA-DR(+)T cells and viral load (R = 0.403, P = 0.03 for the former and R = 0.569, P = 0.09 for the later). CONCLUSIONS: Effective HAART could decrease immune activation of HIV-infected children significantly. And there was a positive correlation between percentage of CD8(+)/CD38(+) and of CD8(+)/HLA-DR(+)T cells and viral load, suggesting that the two indicators might be used as the substitution of viral load in resource-limited areas.

Different plasma levels of interleukins and chemokines: comparison between children and adults with AIDS in China.

BACKGROUND: The immunological differences between children and adults with AIDS in China are not well documented. Th1/Th2 cytokines and chemokines are two types of immune factors intimately involved in disease progression of HIV-1 infection. This study aimed to identify changes in plasma levels of Th1/Th2 cytokines inerleukin (IL)-18, IL-16, IL-10 and chemokines regulated on activation, normal T cell expressed and secreted (RANTES), stromal cell-derived factor-1 (SDF-1) and monocyte chemoattractant protein-1 (MCP-1) in HIV-1-infected children and adults in China. METHODS: Seventy-five children with AIDS and 35 adult AIDS patients were recruited and clinical data were collected. CD4(+) T lymphocyte counts were measured by flow cytometery and plasma HIV RNA levels were measured by quantitative RT-PCR. Plasma levels of IL-18, IL-10, IL-16, RANTES, MCP-1, SDF-1alpha and SDF-1beta were quantified by enzyme-linked immunosorbent assay. The levels of beta2-microglobulin (beta2-MG) and soluble Fas (sFas) were measured to validate the level of humoral and cellular immune activation. RESULTS: The mean levels of all cytokines in pediatric and adult AIDS patients were significantly higher than in their healthy controls (P < 0.01). The mean levels of these cytokines were higher in pediatric patients than in adult patients (P < 0.05, except for SDF-1alpha and beta2-MG). Some of the cytokine levels in patients younger than 6 years old was higher than in older children and adults with AIDS (IL-10, IL-18, SDF-1alpha, MCP, RANTES and sFas, P < 0.05). Levels of IL-18, IL-10, RANTES and beta2-MG of pediatric patients increased as the levels of viral load increased (P < 0.05). CONCLUSIONS: Abnormal immune activation can be measured in Chinese pediatric and adult patients with AIDS, and is higher in children than in adult patients. The cytokines levels coincide with disease progression of AIDS, but have no direct relationship with total CD4(+) T cell count.

[Impact of highly active antiretroviral therapy on plasma MCP-1 and MSP in AIDS patients].

OBJECTIVE: To study the effect of highly active antiretroviral therapy (HAART) on plasma levels of MSP and MCP-1 in AIDS patients. METHODS: Forty Chinese AIDS patients were treated with HAART for 3 months and 84 German AIDS patients with HAART for 3 to 6 years. The pre-treatment and post-treatment plasma levels of MSP and MCP-1 were measured by enzyme-linked immunosorbent assay (ELISA), and their correlations with CD4+ cell counts and viral loads were analyzed. RESULT: The mean levels of MCP-1 were significantly higher and MSP were significantly lower in HIV-infected patients compared with the HIV-negative controls (P <0.01). After HAART for three months, there were no significant changes in the levels of these cytokines. But after long-term HAART (for 3 to 6 y), the level of MCP-1 was increased and that of MSP decreased significantly (P<0.01). There was a negative correlation between MSP and MCP-1 levels, and the same for MSP level and CD4+ cell counts; while there was a positive correlation between MCP-1 levels and CD4+ cell counts. CONCLUSION: The changed plasma levels of MSP and MCP-1 are associated with HIV-1 infection and HAART may reverse the levels of these two cytokines.

[Comparison of immunological profiles between pediatric and adult patients with AIDS in China].

OBJECTIVE: To compare the immunological profiles of pediatric and adult patients with AIDS in China. METHODS: Totally 103 pediatric AIDS patients, 38 adult patients, 88 healthy children, and 72 healthy adults were enrolled. CD4 + T lymphocyte counts were determined by four-color flow cytometer and HIV-RNA levels were measured in EDTA plasma by quantitative reverse-transcription polymerase chain reaction (RT-PCR). Plasma levels of interleukin (IL)-10, IL-16, IL-18, regulated upon activation, normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein 1 (MCP-1), stromal cell-derived factor-(SDF-1) alpha, SDF-1 beta, and macrophage stimulate protein (MSP) were quantified by enzyme-linked immunosorbent assay (ELISA). The levels of beta 2-microglobulin (beta 2-MG) and soluble Fas (sFas) were measured to indicate the activation of immune system. RESULTS: The mean CD4 + T cell count in pediatric patients with AIDS was significantly lower than in healthy children (P < 0.01), as between the adult AIDS patients and healthy adults (P < 0.01). The mean levels of these cytokines in pediatric patients were significantly higher than in healthy children (P < 0.01). The level of MSP in adult patients was significantly lower than in healthy adults and other cytokines were significantly higher (P < 0.01). The mean levels of these cytokines, except SDF1 alpha and beta 2-MG, were significantly higher in pediatric patients than in adult patients (P < 0.01). CONCLUSION: Abnormal immune activation is induced in both pediatric and adult patients with HIV-1 infection. The level of immune activation is higher in pediatric patients than in adult patients.