Generation of cellular immune memory and B-cell immunity is impaired by natural killer cells.

The goal of most vaccines is the induction of long-lived memory T and B cells capable of protecting the host from infection by cytotoxic mechanisms, cytokines and high-affinity antibodies. However, efforts to develop vaccines against major human pathogens such as HIV and HCV have not been successful, thereby highlighting the need for novel approaches to circumvent immunoregulatory mechanisms that limit the induction of protective immunity. Here, we show that mouse natural killer (NK) cells inhibit generation of long-lived virus-specific memory T- and B cells as well as virus-specific antibody production after acute infection. Mechanistically, NK cells suppressed CD4 T cells and follicular helper T cells (T(FH)) in a perforin-dependent manner during the first few days of infection, resulting in a weaker germinal centre (GC) response and diminished immune memory. We anticipate that innovative strategies to relieve NK cell-mediated suppression of immunity should facilitate development of efficacious new vaccines targeting difficult-to-prevent infections.

[Hydrologic processes of the different landscape zones in Fenhe River headwater catchment].

There are few studies on the hydrologic processes of the landscape zone scales at present. Since the water environment is worsening, there is sharp contradiction between supply and demand of water resources in Shanxi province. The principle of the hydrologic processes of the landscape zones in Fenhe River headwater catchment was revealed by means of isotope tracing, hydrology geological exploration and water chemical signal study. The results showed that the subalpine meadow zone and the medium high mountain forest zone were main runoff formation regions in Fenhe River headwater catchment, while the sparse forest shrub zone and the mountain grassland zone lagged the temporal and spatial collection of the precipitation. Fenhe River water was mainly recharged by precipitation, groundwater, melt water of snow and frozen soil. This study suggested that the whole catchment precipitation hardly directly generated surface runoff, but was mostly transformed into groundwater or interflow, and finally concentrated into river channel, completed the "recharge-runoff-discharge" hydrologic processes. This study can provide scientific basis and reference for the containment of water environment deterioration, and is expected to deliver the comprehensive restoration of clear-water reflowing and the ecological environment in Shanxi province.

Preclinical evaluation of a two-dose vaccination schedule of recombinant Hansenula polymorpha hepatitis B vaccine in animals.

AIMS: The current 3-dose regimen of hepatitis B vaccination for infants requiring over 6 mo period may pose the poor rate of compliance and later protection from hepatitis B virus (HBV) infection. This preclinical study is to investigate the feasibility of reducing the number of doses of hepatitis B (HB) vaccine. RESULTS: Eight groups of guinea pigs immunized with two doses of HP-HB vaccines at either 0 and 4 weeks or 0 and 8 weeks elicited geometric titers (GMT) of anti-HBs similar to that of four groups immunized with three doses of controls. The overall GMT of anti-HBs were not significantly different between the E- and C-groups (p>0.05) of monkeys. Specifically, the anti-HBs titers in the C-group reached the peak of 24857 (938.3-104585) mIU/mL one week after the 3rd dose, which were statistically higher than those of the E-group. However, they were reduced to comparable levels of anti-HBs in the E-group during weeks 9-12, suggesting comparable immune response of both vaccination regimens. METHODS: Twelve groups of guinea pigs (four animals in each group) were immunized with 2 experimental recombinant yeast Hansenula Polymorpha derived HB vaccines (HP-HB vaccine) and 2 commercial recombinant yeast Saccharomyces Cerevisiae vaccines (Temrevac-HB) as controls at 0, 4 and 8 weeks, 0 and 4 weeks, and 0 and 8 weeks respectively. Each guinea pig received 2 µg vaccine. Twelve Cynomolgus monkeys were randomly divided into two groups (six animals in each group). Animals in the experimental group (E-group) were injected with two doses of pilot produced 20 µg HP-HB vaccine. Animals in the control group (C-Group) were immunized with three doses of 10 µg Temrevac-HB. Both vaccines were administered at an interval of 3 weeks for monkeys. CONCLUSIONS: The 2-dose regimen of the HP-HB vaccine has comparable HBV immune responses as the 3-dose regimen of Temrevac-HB vaccine in Cynomolgus monkeys.