We used emissivity spectra from the Thermal Emission Spectrometer (TES) to identify the signature of crystalline gray hematite in Capri Chasma. Geologic units associated with major concentrations of ...hematite were then mapped using HiRISE, CRISM, and CTX images from the Mars Reconnaissance Orbiter (MRO). Along the northern portion of the Interior Layered Deposit (ILD), a lower polyhydrated sulfate (PHS) unit lies beneath a thicker kieserite unit, above which is a thinner upper PHS. An exposure at the thickest central portion of the ILD reveals additional sulfates, including a middle PHS, a mixture of lower hydration states PHS, and an intercalated unit comprised of kieserite and szomolnokite. We interpret these compositional transitions to reflect either changes in aqueous chemistry (e.g., iron levels and salinity) during groundwater upwelling events or successively buried layers of dust, ice and volcanic aerosols laid down over obliquity cycles. In addition to these sulfates, we identified a few small mounds along the chasma floor composed of either mixtures of ferric hydroxysulfate and Fe/Mg‐smectites, or possible opal, leached clays, and Fe/Mg‐smectites. Gray hematite is strongly spatially correlated to kieserite‐bearing slopes within the ILD and mantled PHS along the northern chasma floor. These results are consistent with sulfate and hematite formation found elsewhere on Mars, including Meridiani Planum, Aram Chaos, and several other chasmata and chaos regions within Valles Marineris.
Key Points
Several sulfates have been identified and mapped within Capris Chasma
Gray hematite correlates to kieserite and polyhydrated sulfates
Our results are consistent with hematite formation found elsewhere on Mars
Zika virus (ZIKV) infection of pregnant women is associated with congenital Zika syndrome (CZS) and no vaccine is available, although several are being tested in clinical trials. We tested the ...efficacy of ZIKV DNA vaccine VRC5283 in a rhesus macaque model of congenital ZIKV infection. Most animal vaccine experiments have a set pathogen exposure several weeks or months after vaccination. In the real world, people encounter pathogens years or decades after vaccination, or may be repeatedly exposed if the virus is endemic. To more accurately mimic how this vaccine would be used, we immunized macaques before conception and then exposed them repeatedly to ZIKV during early and mid-gestation. In comparison to unimmunized animals, vaccinated animals had a significant reduction in peak magnitude and duration of maternal viremia, early fetal loss, fetal infection, and placental and fetal brain pathology. Vaccine-induced neutralizing antibody titers on the day of first ZIKV exposure were negatively associated with the magnitude of maternal viremia, and the absence of prolonged viremia was associated with better fetal outcomes. These data support further clinical development of ZIKV vaccine strategies to protect against negative fetal outcomes.
Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and ...lower airways is important to evaluate in nonhuman primates.
Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens.
The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID
) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)-biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group.
Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.).
Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 μg of the mRNA-1273 ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti–S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273–induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine–induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.
Computational vaccinology includes epitope mapping, antigen selection, and immunogen design using computational tools. Tools that facilitate the
prediction of immune response to biothreats, emerging ...infectious diseases, and cancers can accelerate the design of novel and next generation vaccines and their delivery to the clinic. Over the past 20 years, vaccinologists, bioinformatics experts, and advanced programmers based in Providence, Rhode Island, USA have advanced the development of an integrated toolkit for vaccine design called iVAX, that is secure and user-accessible by internet. This integrated set of immunoinformatic tools comprises algorithms for scoring and triaging candidate antigens, selecting immunogenic and conserved T cell epitopes, re-engineering or eliminating regulatory T cell epitopes, and re-designing antigens to induce immunogenicity and protection against disease for humans and livestock. Commercial and academic applications of iVAX have included identifying immunogenic T cell epitopes in the development of a T-cell based human multi-epitope Q fever vaccine, designing novel influenza vaccines, identifying cross-conserved T cell epitopes for a malaria vaccine, and analyzing immune responses in clinical vaccine studies. Animal vaccine applications to date have included viral infections of pigs such as swine influenza A, PCV2, and African Swine Fever. "Rapid-Fire" applications for biodefense have included a demonstration project for Lassa Fever and Q fever. As recent infectious disease outbreaks underscore the significance of vaccine-driven preparedness, the integrated set of tools available on the iVAX toolkit stand ready to help vaccine developers deliver genome-derived, epitope-driven vaccines.
Disposable materials contribute to healthcare's estimated production of 33 pounds of waste per patient bed per day or approximately 5.9 million tons of waste each year. The shift toward disposable ...materials was initially driven by a variety of factors including the potential for infection control, convenience, and cost. The current use of single-use disposables in healthcare, however, has become costly, wasteful, and to some extent, unnecessary. Disposable custom packs, a set of products prepackaged for a specific procedure to reduce time and error, are utilized in nearly every medical procedure performed in the US and internationally. This study analyzed 15 custom packs from geographically diverse hospitals using life cycle assessment and design for the environment. Polypropylene, the material used to make gowns and drapes, was the most prominent material by weight, followed by cotton. However, the life cycle assessment results show that cotton composed the largest portion of environmental impacts in every category. Finally, a new green custom pack was designed. By using tools and strategies such as life cycle assessment and design for the environment, healthcare institutions can make educated streamlining efforts for their disposable custom packs.
•Custom packs are used in many healthcare procedure and streamlining efforts may offer environmental and economic savings.•Cotton products in the healthcare industry should be considered for reuse and not discarded after one use.•By using life cycle assessment and design for the environment, healthcare institutions can make environmental improvements.
We describe the demographics of the decedents from the tornado outbreak in Alabama on April 27, 2011; examine the circumstances of death surrounding these fatalities; and identify measures to prevent ...future tornado-related fatalities.
We collected information about the decedents from death certificates, disaster-related mortality surveillance, and interview data collected by American Red Cross volunteers from the decedent's families. We describe demographic characteristics, circumstances and causes of death, and sheltering behaviors before death.
Of the 247 fatalities, females and older adults were at highest risk for tornado-related deaths. Most deaths were directly related to the tornadoes, on scene, and trauma-related. The majority of the deceased were indoors in single-family homes. Word of mouth was the most common warning mechanism.
This tornado event was the third deadliest in recent US history. Our findings support the need for local community shelters, enhanced messaging to inform the public of shelter locations, and encouragement of word-of-mouth warnings and personal and family preparedness planning, with a special focus on assisting vulnerable individuals in taking shelter.
Recent studies have shown that immune responses against the cell-traversal protein for Plasmodium ookinetes and sporozoites (CelTOS) can inhibit parasite infection. While these studies provide ...important evidence toward the development of vaccines targeting this protein, it remains unknown whether these responses could engage the Plasmodium falciparum CelTOS in vivo Using a newly developed rodent malaria chimeric parasite expressing the P. falciparum CelTOS (PfCelTOS), we evaluated the protective effect of in vivo immune responses elicited by vaccination and assessed the neutralizing capacity of monoclonal antibodies specific against PfCelTOS. Mice immunized with recombinant P. falciparum CelTOS in combination with the glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) or glucopyranosyl lipid adjuvant-liposome-QS21 (GLA-LSQ) adjuvant system significantly inhibited sporozoite hepatocyte infection. Notably, monoclonal antibodies against PfCelTOS strongly inhibited oocyst development of P. falciparum and Plasmodium berghei expressing PfCelTOS in Anopheles gambiae mosquitoes. Taken together, our results demonstrate that anti-CelTOS responses elicited by vaccination or passive immunization can inhibit sporozoite and ookinete infection and impair vector transmission.
The circumsporozoite protein (CSP) of Plasmodium falciparum is a major surface protein, which forms a dense coat on the sporozoite's surface. Preclinical research on CSP and clinical evaluation of a ...CSP fragment-based RTS, S/AS01 vaccine have demonstrated a modest degree of protection against P. falciparum, mediated in part by humoral immunity and in part by cell-mediated immunity. Given the partial protective efficacy of the RTS, S/AS01 vaccine in a recent Phase 3 trial, further improvement of CSP-based vaccines is crucial. In this report, we describe the preclinical development of a full-length, recombinant CSP (rCSP)-based vaccine candidate against P. falciparum malaria suitable for current Good Manufacturing Practice (cGMP) production. Utilizing a novel high-throughput Pseudomonas fluorescens expression platform, we demonstrated greater efficacy of full-length rCSP as compared to N-terminally truncated versions, rapidly down-selected a promising lead vaccine candidate, and developed a high-yield purification process to express immunologically active, intact antigen for clinical trial material production. The rCSP, when formulated with various adjuvants, induced antigen-specific antibody responses as measured by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA), as well as CD4+ T-cell responses as determined by ELISpot. The adjuvanted rCSP vaccine conferred protection in mice when challenged with transgenic P. berghei sporozoites containing the P. falciparum repeat region of CSP. Furthermore, heterologous prime/boost regimens with adjuvanted rCSP and an adenovirus type 35-vectored CSP (Ad35CS) showed modest improvements in eliciting CSP-specific T-cell responses and anti-malarial protection, depending on the order of vaccine delivery. Collectively, these data support the importance of further clinical development of adjuvanted rCSP, either as a stand-alone product or as one of the components in a heterologous prime/boost strategy, ultimately acting as an effective vaccine candidate for the mitigation of P. falciparum-induced malaria.
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