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SARS-CoV-2 continues to pose a threat to human health as new variants emerge and thus a diverse vaccine pipeline is needed. We evaluated SARS-CoV-2 HexaPro spike protein formulated in Alhydrogel ® (aluminium oxyhydroxide) in Syrian hamsters, using an accelerated two dose regimen (given 10 days apart) and a standard regimen (two doses given 21 days apart). Both regimens elicited spike- and RBD-specific IgG antibody responses of similar magnitude, but in vitro virus neutralization was low or undetectable. Despite this, the accelerated two dose regimen offered reduction in viral load and protected against lung pathology upon challenge with homologous SARS-CoV-2 virus (Wuhan-Hu-1). This highlights that vaccine-induced protection against SARS-CoV-2 disease can be obtained despite low neutralizing antibody levels and suggests that accelerated vaccine schedules may be used to confer rapid protection against SARS-CoV-2 disease.

Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationic liposomes containing dimethyldioctadecylammonium bromide (DDA) and Trehalose-6,6-dibehenate (TDB)) with the lipidated TLR7/8 agonist 3M-052 (DDA/TDB/3M-052), which promoted robust Th1 immunity in newborn mice. When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-γ+Th1 response in a TLR7 agonist dose-dependent manner. Single-cell RNA-sequencing revealed that DDA/TDB/3M-052 liposomes initiated early transcription of class-switch regulating genes directly in pre-germinal center B cells. Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T-cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses.

The material basis of a sustainable society will depend on chemical products and processes that are designed following principles that make them conducive to life. Important inherent properties of molecules need to be considered from the earliest stage—the design stage—to address whether compounds and processes are depleting versus renewable, toxic versus benign, and persistent versus readily degradable. Products, feedstocks, and manufacturing processes will need to integrate the principles of green chemistry and green engineering under an expanded definition of performance that includes sustainability considerations. This transformation will require the best of the traditions of science and innovation coupled with new emerging systems thinking and systems design that begins at the molecular level and results in a positive impact on the global scale.

► The supply of external nitrogen to microalgae cultivation is energy intensive. ► Recycling the nitrogen contained in the non-triacylglyceride portion of microalgae may circumvent the negative energy impacts associated with external nitrogen supply. ► Decisions on how to reuse nitrogen must be made within the context of the overall energy balance, sustainability, and commercialization potential of the microalgae biorefinery. Favorable growth characteristics continue to generate interest in using triacylglycerides (TAGs) produced from microalgae for biodiesel feedstocks. In this opinion article, we suggest that due to the energy consumption associated with the production of external nitrogen fertilizers, the manner in which nitrogen is supplied to microalgae biorefineries will be an important driver of energy yields, sustainability, and commercial success. Schemes including the reuse of urban wastewater represent improvements on the overall energy balance, but will not allow for significant production of biofuels unless the nitrogen from the non-TAG portions of microalgae is recycled. Approaches to recycling nitrogen require an improved understanding of the tradeoffs between the different potential uses of the non-TAG microalgal portion (i.e., energy production via anaerobic digestion or thermal catalytic processes), and the development of nitrogen separation technologies.

Therapeutic vaccines capable of eliciting CD8 T cell responses are a promising approach in cancer, but the magnitude of immune responses to peptide-based vaccine technologies has so far been modest in humans. The cationic liposome adjuvant CAF®09b has recently shown promising results in clinical trials, where it is administered intraperitoneally (i.p.), as preclinical studies demonstrated superior CD8 T cell responses when using this route compared to subcutaneous delivery. Exploring the mechanism of CAF09b in mice we investigated biodistribution of the adjuvant and associated antigen in murine studies. We further examined local innate cell recruitment and CD8 T cell responses in the peritoneal cavity. We observed that i.p. injected CAF09b associated with visceral fatty tissues and created a vaccine depot in the peritoneal cavity. This led to recruitment of BATF3-dependent conventional type I dendritic cells (cDC1) displaying a migratory cDC1 phenotype (CD11c+XCR1+CD103+). Gene ontology analysis further revealed similarities with visceral adipose tissue DCs. CAF09b injection i.p. led to early priming of CD8 T cells localized to the peritoneal cavity and this response was resistant to FTY720 treatment. This study demonstrates that adjuvants can facilitate recruitment of cDC1s to the peritoneal cavity, a feature that may contribute to the effectiveness of i.p. administration on elicitation of CD8 T cell responses. Furthermore, we demonstrate that CAF09b-induced CD8 T cell responses require BATF3-dependent cDC1 cells. Understanding cDC1 and CD8 T cell dynamics via different immunization routes may aid in the design of more effective vaccine strategies. This work was primarily supported by the Danish Research Council (FTP fund no. 9041-00131b). •Adjuvants administered i.p. effectively recruits migratory cDC1 cells to the peritoneal cavity.•Intraperitoneal injection of CAF09b induces bone marrow mobilization of cDC1 progenitors.•CAF09b injection i.p. led to early priming of CD8 T cells localized to the peritoneal cavity.•Priming of CD8 T cell responses by CAF09b requires cDC1 cells.

Zooarchaeological hypotheses concerning prehistoric transport, processing decisions, and social stratification are often tested by correlating archaeological element frequencies with indices of the economic utility of carcass parts. Such indices have not been developed for one of the largest and most important mammals in Eastern Woodlands prehistory, the white-tailed deer (Odocoileus virginianus). We present kilocalorie (Kcal) yields and return rates of meat and marrow from a sample of several white-tailed deer. We then compare the meat and marrow data with skeletal element abundance in two Late Archaic assemblages from New York and a Middle Woodland/early Late Woodland assemblage from Illinois. In both examples, archaeological element abundance is positively correlated with marrow yield and return rate, but negatively correlated or uncorrelated with meat yield and return rate. These results do not provide evidence for differential transport of higher meat-yield carcass parts, but instead may indicate differential processing of high-yield marrow bones after entire deer carcasses were transported to the sites.

The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future respiratory virus pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CAF®09b contains the TLR3 agonist polyinosinic:polycytidylic acid, which induces a type I interferon (IFN-I) response and an antiviral state in the affected tissues. When testing CAF09b liposomes as a potential pan-viral prophylaxis, we observed that intranasal administration of CAF09b liposomes to mice resulted in an influx of innate immune cells into the nose and lungs and upregulation of IFN-I-related gene expression. When CAF09b liposomes were administered prior to challenge with mouse-adapted influenza A/Puerto Rico/8/1934 virus, it protected from severe disease, although the virus was still detectable in the lungs. However, when CAF09b liposomes were administered after influenza challenge, the mice had a similar disease course to controls. In conclusion, CAF09b may be a suitable candidate as a pan-viral prophylactic treatment for epidemic viruses, but must be administered prior to virus exposure to be effective.

Archaeologists often portray Cahokia as the center of a chiefdom. A minority view is that Cahokia was the center of a state. These competing views are considered here, and an alternative model is presented, that Cahokia might be considered the center of a theater state. This model agrees with other models that Cahokia was an economic and political center, but also emphasizes Cahokia's role as a center of ritual. In the theater state model, the power of a state lies more in its ceremonies than in its armies. People came to Cahokia, helping to build it and feed it, not because they were coerced but because they wanted to be part of the drama. This view of Cahokia is not presented in order to replace all other models but, rather, to stimulate archaeologists to rethink what Cahokia might have been like. Geertz's theater state model suggests an alternative, non-Western view of the state that might be useful in reconsidering other archaeological complex societies as well.

The Carter Creek site (11-Md-817) was a village located at the prairie edge in west central Illinois during the early Late Woodland Weaver phase (Esarey et al. 1984). This occupation represents a frontier upland community (Green 1987, 1993). Animal remains recovered from the Carter Creek site are compared to contemporaneous samples from the region in order to test hypotheses proposed by Green (1987, 1993) and Styles (2000). It is found that the \"pioneers\" at Carter Creek continued to hunt and fish as their ancestors had (cf. Green 1987, 1993), but with some adjustments to optimize local resources (cf. Styles 2000). There is no evidence of venison trading or tribute found at this or any contemporaneous sites.