Archaeal glycolipid adjuvanted vaccines induce strong influenza-specific immune responses through direct immunization in young and aged mice or through passive maternal immunization.

Vaccine induced responses are often weaker in those individuals most susceptible to infection, namely the very young and the elderly, highlighting the need for safe and effective vaccine adjuvants. Herein we evaluated different archaeosome formulations as an adjuvant to the H1N1 influenza hemagglutinin protein and compared immune responses (anti-HA IgG and hemagglutination inhibition assay titers) as well as protection to an influenza A virus (strain A/Puerto Rico/8/1934 H1N1) homologous challenge to those generated using a squalene-based oil-in-water nano-emulsion, AddaVax™ in a murine model. The impact of age (young adult vs aged) on vaccine induced immune responses as well as the protection in pups due to the transfer of maternal antibodies was measured. Overall, we show that archaeal lipid based adjuvants can induce potent anti-HA responses in young and aged mice that can also be passed from vaccinated mothers to pups. Furthermore, young and aged mice immunized with archaeal lipid adjuvants as well as pups from immunized mothers were protected from challenge with influenza. In addition, we show that a simple admixed archaeosome formulation composed of a single sulfated glycolipid namely sulfated lactosylarchaeol (SLA; 6′-sulfate-β-D-Galp-(1,4)-β-D-Glcp-(1,1)-archaeol) can give equal or better protection compared to AddaVax™ or the traditional antigen-encapsulated archaeosome formulations

Placental Infection by Salmonella Typhimurium in a Murine Model: The Role of Innate Immune Mediators in Cell Death at the Fetal-Maternal Interface

Maternal tolerance during pregnancy increases the risk of infection with certain intracellular pathogens such as Salmonella enterica serovar Typhimurium (S.Tm). Systemic S.Tm infection during pregnancy in normally resistant 129X1/SvJ mice, with a functional natural resistance-associated macrophage protein-1 (Nramp1), leads to severe placental infection followed by fetal and maternal death. We hypothesized infection-induced inflammatory trophoblast cell death contributes to adverse pregnancy outcomes. We therefore investigated the kinetics of systemic and oral S.Tm infection in wild-type and gene deficient mice with defects in specific inflammatory pathways. Systemic infection with S.Tm resulted in preferential placental replication compared to other tissues in Nramp1+/+ mice. At 24 hours, <25% of individual placentas per mouse were infected, progressively increasing to >75% by 72 hours which correlated with a steady increase in resorption rates. Moreover, placental infection was associated with increased neutrophils, macrophages and natural killer cells whereas neutrophil numbers in the spleen remained unchanged, suggesting dichotomous modulation of inflammation in the systemic compartment compared to the feto-maternal interface. Oral infection resulted in systemic dissemination of the bacteria, substantial placental colonization and fetal loss five days post-infection in C57BL/6J mice. Systemic infection in pregnant cell death deficient Rip3-/-Nramp1+/+ mice (with defective necroptosis) resulted in decreased fetal demise relative to Nramp1+/+ and Caspase-1,11-/-Nramp1+/+ mice (with defective pyroptosis) suggesting a role for necroptotic inflammation. This study provides insight into the kinetics and mechanism of inflammation and cell death during placental S.Tm infection. Such studies may assist in the rational management of foodborne pathogens contracted during pregnancy

Placental infection by Salmonella enterica typhimurium in a murine model : mechanisms of pathogenesis and role of inflammatory cell death

Pregnancy confers increased susceptibility to intracellular infections such as Salmonella enterica serovar Typhimurium (S. Tm). S. Tm infection during pregnancy in normally resistant mice (129X1/SvJ with a fully functional Nramp gene) leads to rapid severe placental inflammation followed by fetal and maternal death. However, the immune mechanism of feto-maternal interface inflammation has not been fully elucidated. The objective of this study was to test the hypothesis that the mechanism of trophoblast (TBC) cell death following infection, contributes to feto-maternal inflammation and adverse effects on the mother and fetus.Peer reviewed: YesNRC publication: Ye