1.
Crystal structure of the Mycobacterium tuberculosis phosphate binding protein PstS3.
Ferraris, DM, Spallek, R, Oehlmann, W, Singh, M, Rizzi, M
Proteins. 2014;(9):2268-74
Abstract
Mycobacterium tuberculosis evades host immune responses by colonizing macrophages. Intraphagosomal M. tuberculosis is exposed to environmental stresses such as reactive oxygen and nitrogen intermediates as well as acid shock and inorganic phosphate (Pi) depletion. Experimental evidence suggests that expression levels of mycobacterial protein PstS3 (Rv0928) are significantly increased when M. tuberculosis bacilli are exposed to Pi starvation. Hence, PstS3 may be important for survival of Mtb in conditions where there is limited supply of Pi. We report here the structure of PstS3 from M. tuberculosis at 2.3-Å resolution. The protein presents a structure typical for ABC phosphate transfer receptors. Comparison with its cognate receptor PstS1 showed a different pattern distribution of surface charges in proximity to the Pi recognition site, suggesting complementary roles of the two proteins in Pi uptake.
2.
A dose-ranging study of a subunit Respiratory Syncytial Virus subtype A vaccine with and without aluminum phosphate adjuvantation in adults > or =65 years of age.
Langley, JM, Sales, V, McGeer, A, Guasparini, R, Predy, G, Meekison, W, Li, M, Capellan, J, Wang, E
Vaccine. 2009;(42):5913-9
Abstract
We studied the safety and immunogenicity of a Respiratory Syncytial Virus (RSV)-A vaccine containing subunit antigens F, G and M in older persons, and its effect on influenza vaccine immunogenicity. In a dose-ranging, placebo-controlled, blinded trial 561 adults > or =65 years of age at five Canadian sites were randomized to one intramuscular injection of either 100, 50 or 25 microg RSV-A-alum vaccine or 100 microg non-adjuvanted RSV-A vaccine, or alum-placebo. All participants were offered inactivated influenza vaccine on day 32. Immunization was well tolerated and reactogenicity was similar between the RSV and influenza vaccines and the alum-placebo. Only the 100 microg non-adjuvanted RSV vaccine achieved the primary immunogenicity outcome of eliciting a > or =4-fold rise in neutralizing antibody (NA) titres against RSV-A in > or =50% of participants at day 32. Geometric mean titres against RSV-A and -B at all points were comparable in 100 microg adjuvanted and non-adjuvanted groups. At day 32, a > or =4-fold haemagluttinin inhibition (HI) antibody response or HI > or =40 to Influenza (A-H3N2) was seen in >74% of participants; no difference was seen between groups. A subunit non-alum-containing RSV-A vaccine was well tolerated in a large population > or =65 years and did not interfere with influenza vaccine immunogenicity. This RSV-A-based vaccine demonstrated NA rise which could provide seasonal protection against severe RSV illnesses from RSV-A or -B and warrants further testing to determine its efficacy in the prevention of clinical illness in elderly persons.