Highly effective generic adjuvant systems for orphan or poverty-related vaccines

Safe and effective adjuvants are needed for many vaccines with limited commercial appeal, such as vaccines to infrequent (orphan) diseases or to neglected and poverty-related diseases. Here we found that three nonproprietary liposome formulations containing monophosphoryl lipid A each induced 3-fold to 5-fold increased titers of binding and neutralizing antibodies to anthrax protective antigen compared to aluminum hydroxide-adsorbed antigen in monkeys. All vaccinated monkeys were protected against lethal challenge with aerosolized Ames strain spores.     

The level of B7 homologue 1 expression on brain DC is decisive for CD8 Treg cell recruitment into the CNS during EAE

DC in the CNS have emerged as the major rate‐limiting factor for immune invasion and subsequent neuroinflammation during EAE. The mechanism of how this is regulated by brain‐localized DC remains unknown. Here, we describe the ability of brain‐localized DC expressing B7‐H1 molecules to recruit CD8⁺ T cells to the site of inflammation. Using intracerebral microinjections of B7‐homologue 1‐deficient DC, we demonstrate a substantial brain infiltration of CD8⁺ T cells displaying a regulatory phenotype (CD122⁺) and function, resulting in a decrease of EAE peak clinical values. The recruitment of regulatory‐type CD8⁺ T cells into the CNS and the role of brain DC expressing B7‐homologue 1 molecules in this process open up the possibility of DC‐targeted therapeutic manipulation of neuroinflammatory diseases.     

The importance of antibody isotype in HIV-1 virus capture assay and in TZM-bl neutralization

The binding of murine IgM mAbs to five different clades of HIV-1 was examined using a modified ELISA-based virus capture assay. Two murine multispecific IgM mAbs that exhibit both lipid and gp41 epitope specificities, and one murine IgM mAb that exhibits lipid-binding specificity, were utilized. The binding of the IgG and the IgM isotypes of human mAb 2F5 to clades A through AE were also evaluated. The binding of 2F5 to HIV-1 was dependent upon the antibody isotype. Monoclonal IgM antibodies bound significantly lower amounts of HIV-1 than the corresponding IgG isotype. Although murine IgM mAbs bound HIV-1 to varying degrees in the virus capture assay, they failed to neutralize HIV-1 in a TZM-bl pseudovirus assay. In contrast, 2F5-IgM mAb bound certain HIV-1 isolates, and also neutralized them, although not as efficiently as the 2F5-IgG isotype. Studies on the relationship between virus binding and neutralization in a TZM-bl pseudovirus assay indicated that in most cases, mAbs that exhibited neutralization also bound the virus.     

Correlation between lethal toxin-neutralizing antibody titers and protection from intranasal challenge with Bacillus anthracis Ames strain spores in mice after transcutaneous immunization with recombinant anthrax protective antigen

Transcutaneous immunization of mice with recombinant protective antigen (rPA) of Bacillus anthracis resulted in significantly higher lethal toxin-neutralizing antibody titers than did intramuscular injection of alum-adsorbed rPA. Immunized mice were partially protected against intranasal challenge with 235,000 (10 50% lethal doses) Ames strain B. anthracis spores. A highly significant correlation was observed between toxin-neutralizing antibody titer and survival after challenge. Future experiments with rabbits and nonhuman primates should confirm the significance of protection by this vaccine strategy.     

Possible role of natural killer and natural killer T-like cells in implantation failure after IVF

During implantation, maternal immunoactivation and tolerance are not only limited to the decidua but are also observed in the periphery, predominantly affecting the innate immune system. Since unexplained female infertility, as well as recurrent spontaneous abortion and implantation failure, are thought to be associated with pathological maternal immunotolerance mechanisms, this study focused on immune profile analysis of IVF candidates. Previous studies on peripheral natural killer (NK) cell characteristics of IVF patients have been limited to the comparison of blood samples taken prior to the IVF procedure. This study performed a follow-up study and compared patient's data obtained on the day of oocyte collection with the data 1 week after embryo transfer. The aim was to investigate phenotypic (subpopulations, CD69, T-cell immunoglobulin mucin 3 and NK-activating receptor expression) and functional (perforin and CD107a expression) changes in the peripheral NK and NK T (NKT)-like cell populations. During this short period of time around the IVF procedure, women with failed IVF reflected unfavourable Th1-oriented changes of NK and NKT-like cells. In comparison the follow-up data for women with successful conception remained principally constant. The observed peripheral changes during early pregnancy in the same individual may also have importance in successful embryo implantation.     

Postural control in standing following stroke: test-retest reliability of some quantitative clinical tests

Despite their importance to stroke rehabilitation, appropriate clinical tests of postural control in standing appear to be inadequately developed. Several quantitative clinical tests, therefore, were constructed. These tests were used to measure functionally relevant aspects of postural control in standing in 24 stroke patients within a mean time interval of two months following a cerebrovascular accident. Subjects were tested in two stance positions (step and parallel) for five tasks that assessed their ability to withstand perturbations produced by self-generated body movements during functional activities. Intrasession reliability coefficients were very high (r = .94-.99). Intersession reliability coefficients were also high (r = .85-.94). Because the test battery requires minimal training and equipment, it can be easily applied in the clinical setting. The high reliability obtained justifies further evaluation of these tests, which appear to be very promising for use in stroke rehabilitation.