Adjuvants enhance both the magnitude and duration of immune responses, therefore representing a central component of vaccines. The nature of the adjuvant can determine the particular type of immune response, which may be skewed toward cytotoxic T cell (CTL) responses, antibody responses, or particular classes of T helper (Th) responses and antibody isotypes. Traditionally, adjuvants have been added to intrinsically poor immunogenic vaccines, such as those using whole killed organisms or subunit vaccines. Here, we have compared cellular immune responses induced by the immunogenic modified life-attenuated vaccine Ingelvac PRRS® MLV when administered alone or in combination with carbopol, a widely used adjuvant in veterinary medicine. Using functional readouts (IFN-γ ELISpot and cell proliferation) and analyzing phenotypical hallmarks of CD4T cell differentiation, we show that carbopol improves cellular immunity by inducing early IFN-γ-producing cells and by preferentially driving T cell differentiation to effector phenotypes. Our data suggest that adjuvants may enhance and modulate life-attenuated--not only subunit/inactivated--vaccines.

In 2012, approximately 5.6 million Zambians did not have access to improved sanitation and around 2.1 million practiced open defecation. The Zambia Sanitation and Hygiene Program (ZSHP), featuring community-led total sanitation, began in November 2011 to increase the use of improved sanitation facilities and adopt positive hygiene practices. Using a pre-and post-design approach with a population-level survey, after 3 years of implementation, we evaluated the impact of ZSHP in randomly selected households in 50 standard enumeration areas (representing 26 of 65 program districts). We interviewed caregivers of children younger than 5 years old (1,204 and 1,170 female caregivers at baseline and end line, respectively) and inspected household toilet facilities and sites for washing hands. At end line, 80% of households had access to improved sanitation facilities versus 64.1% at baseline (prevalence ratio [PR] = 1.25; 95% CI: 1.18-1.31) and 14.1% did not have a toilet facility compared with 19.4% at baseline. At end line, 10.6% of households reported living in an open defecation-free certified village compared with 0.3% at baseline (PR = 32.0; 95% CI: 11.9-86.4). In addition, at end line, 33.4% of households had a specific place for washing hands and 61.4% of caregivers reported handwashing with a washing agent after defecation or before preparing food compared with 21.1% (PR = 1.59; 95% CI: 1.39-1.82) and 55.2% (PR = 1.11; 95% CI: 1.04-1.19) at baseline, respectively. Community-led total sanitation implementation in Zambia led to improvements in access to improved sanitation facilities, reduced open defecation, and better handwashing practices. There is however a need for enhanced investment in sanitation and hygiene promotion.

Defects in the generation and transport of antigenic peptides within tumor cells will lead to the expression of unstable HLA-class-I molecules on the cell surface. These defects will allow tumor cells to escape an MHC-class-I-restricted T-cell response. Recently, we described an exclusively HLA-class-II-restricted autologous T-cell response against a human sarcoma cell line MZ-MES-1 in vitro. Here, we show that surface HLA-class-I molecules of MZ-MES-1 cells are unstable at physiological temperature. HLA-class-I surface expression of MZ-MES-1 cells could be strongly enhanced by culture at low temperature in contrast to various other cell lines analyzed in parallel. Furthermore, culture at low temperature decreased shedding of HLA-class-I molecules by MZ-MES-1 cells. Incubation with allele-specific HLA-class-I-binding peptides strongly increased HLA-class-I surface expression of MZ-MES-1 sarcoma cells and TAP-deficient T2 cells in contrast to other tumor and B-cell lines tested in parallel. IFN-gamma enhanced the expression of TAP, LMP and HLA-class-I proteins in MZ-MES-1 cells. However, the impaired stability of HLA-class-I surface molecules of MZ-MES-1 could not be reversed by IFN-gamma. These results show a new example of impaired HLA-class-I stability of a human tumor which coincides with lack of HLA-class-I-restricted autologous T cells recognizing this tumor. It underlines the importance of MHC-class-II-restricted T-cell responses against tumors with these defects.

No abstract