Quantitation of CD8+ T Cell Responses to Newly Identified HLA-A*0201–restricted T Cell Epitopes Conserved Among Vaccinia and Variola (Smallpox) Viruses

Immunization with vaccinia virus resulted in long-lasting protection against smallpox and was the approach used to eliminate natural smallpox infections worldwide. Due to the concern about the potential use of smallpox virus as a bioweapon, smallpox vaccination is currently being reintroduced. Severe complications from vaccination were associated with congenital or acquired T cell deficiencies, but not with congenital agammaglobulinemia, suggesting the importance of T cell immunity in recovery from infection. In this report, we identified two CD8+ T cell epitopes restricted by the most common human major histocompatibility complex (MHC) class I allele, HLA-A*0201. Both epitopes are highly conserved in vaccinia and variola viruses. The frequency of vaccinia-specific CD8+ T cell responses to these epitopes measured by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay and HLA/peptide tetramer staining peaked 2 wk after primary immunization and then declined, but were still detectable 1 to 3 yr after primary immunization. 2 wk after immunization, IFN-γ–producing cells specific to these two epitopes were 14% of total vaccinia virus-specific IFN-γ–producing cells in one donor, 35% in the second donor, and 6% in the third donor. This information will be useful for studies of human T cell memory and for the design and analyses of the immunogenicity of experimental vaccinia vaccines

Dose-related effects of smallpox vaccine

BACKGROUND: We conducted a double-blind, randomized trial of three dilutions of vaccinia virus vaccine in previously unimmunized adults in order to assess the clinical success rates, humoral responses, and virus-specific activity of cytotoxic T cells and interferon-gamma-producing T cells. METHODS: Sixty healthy adults were inoculated intradermally by bifurcated needle with undiluted vaccine (dose, 10(7.8) plaque-forming units [pfu] per milliliter), a 1:10 dilution (dose, 10(6.5) pfu per milliliter), or a 1:100 dilution (dose, 10(5.0) pfu per milliliter); there were 20 subjects in each group. The subjects were monitored with respect to vesicle formation (an indicator of successful vaccination), the viral titer at the time of peak lesion formation, antiviral antibodies, and cellular immune responses. RESULTS: A vaccinia vesicle developed in 19 of the 20 subjects who received undiluted vaccine (95 percent), 14 of the 20 who received the 1:10 dilution (70 percent), and 3 of the 20 who received the 1:100 dilution (15 percent). One month after vaccination, 34 of 36 subjects with vesicles had antibody responses, as compared with only 1 of 24 subjects without clinical evidence of vaccinia virus replication. Vigorous cytotoxic T-cell and interferon-gamma responses occurred in 94 percent of subjects with vesicles, and a cytotoxic T-cell response occurred in only one subject without a vesicle. CONCLUSIONS: The vaccinia virus vaccine (which was produced in 1982 or earlier) still has substantial potency when administered by a bifurcated needle to previously unvaccinated adults. Diluting the vaccine reduces the rate of successful vaccination. The development of vesicular skin lesions after vaccination correlates with the induction of the antibody and T-cell responses that are considered essential for clearing vaccinia virus infections

Therapy and Long-Term Prophylaxis of Vaccinia Virus Respiratory Infections in Mice with an Adenovirus-Vectored Interferon Alpha (mDEF201)

An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal vaccinia virus (WR strain) respiratory infections in mice. mDEF201 was administered as a single intranasal treatment either prophylactically or therapeutically at doses of 106 to 108 plaque forming units/mouse. When the prophylactic treatment was given at 56 days prior to infection, it protected 90% of animals from death (100% protection for treatments given between 1–49 days pre-infection), with minimal weight loss occurring during infection. Surviving animals re-challenged with virus 22 days after the primary infection were protected from death, indicating that mDEF201 did not compromise the immune response against the initial infection. Post-exposure therapy was given between 6–24 h after vaccinia virus exposure and protection was afforded by a 108 dose of mDEF201 given at 24 h, whereas a 107 dose was effective up to 12 h. Comparisons were made of the ability of mDEF201, given either 28 or 1 day prior to infection, to inhibit tissue virus titers and lung infection parameters. Lung, liver, and spleen virus titers were inhibited to nearly the same extent by either treatment, as were lung weights and lung hemorrhage scores (indicators of pneumonitis). Lung virus titers were significantly (>100-fold) lower than in the placebo group, and the other infection parameters in mDEF201 treated mice were nearly at baseline. In contrast, viral titers and lung infection parameters were high in the placebo group on day 5 of the infection. These results demonstrate the long-acting prophylactic and treatment capacity of mDEF201 to combat vaccinia virus infections

Soil sedimentology at Gusev Crater from Columbia Memorial Station to Winter Haven

A total of 3140 individual particles were examined in 31 soils along Spirit’s traverse. Their size, shape, and texture were quantified and classified. They represent a unique record of 3 years of sedimentologic exploration from landing to sol 1085 covering the Plains Unit to Winter Haven where Spirit spent the Martian winter of 2006. Samples in the Plains Unit and Columbia Hills appear as reflecting contrasting textural domains. One is heterogeneous, with a continuum of angular-to-round particles of fine sand to pebble sizes that are generally dust covered and locally cemented in place. The second shows the effect of a dominant and ongoing dynamic aeolian process that redistributes a uniform population of medium-size sand. The texture of particles observed in the samples at Gusev Crater results from volcanic, aeolian, impact, and water-related processes

Use of Recombinant Adenovirus Vectored Consensus IFN-α to Avert Severe Arenavirus Infection

Several arenaviruses can cause viral hemorrhagic fever, a severe disease with case-fatality rates in hospitalized individuals ranging from 15-30%. Because of limited prophylaxis and treatment options, new medical countermeasures are needed for these viruses classified by the National Institutes of Allergy and Infectious Diseases (NIAID) as top priority biodefense Category A pathogens. Recombinant consensus interferon alpha (cIFN-α) is a licensed protein with broad clinical appeal. However, while cIFN-α has great therapeutic value, its utility for biodefense applications is hindered by its short in vivo half-life, mode and frequency of administration, and costly production. To address these limitations, we describe the use of DEF201, a replication-deficient adenovirus vector that drives the expression of cIFN-α, for pre- and post-exposure prophylaxis of acute arenaviral infection modeled in hamsters. Intranasal administration of DEF201 24 h prior to challenge with Pichindé virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver-associated disease. A significant protective effect was still observed with a single dosing of DEF201 given two weeks prior to PICV challenge. DEF201 was also efficacious when administered as a treatment 24 to 48 h post-virus exposure. The protective effect of DEF201 was largely attributed to the expression of cIFN-α, as dosing with a control empty vector adenovirus did not protect hamsters from lethal PICV challenge. Effective countermeasures that are highly stable, easily administered, and elicit long lasting protective immunity are much needed for arena and other viral infections. The DEF201 technology has the potential to address all of these issues and may serve as a broad-spectrum antiviral to enhance host defense against a number of viral pathogens

Hydrothermal origin of halogens at Home Plate, Gusev Crater

In the Inner Basin of the Columbia Hills, Gusev Crater is Home Plate, an 80 m platform of layered clastic rocks of the Barnhill class with microscopic and macroscopic textures, including a bomb sag, suggestive of a phreatomagmatic origin. We present data acquired by the Spirit Mars Exploration Rover by Alpha Particle X-Ray Spectrometer (APXS), Mössbauer Spectrometer, Miniature Thermal Emission Spectrometer (Mini- TES), and Panoramic Camera (Pancam) for the Barnhill class rocks and nearby vesicular Irvine class basalts. In major element concentrations (e.g., SiO2, Al2O3, MgO, and FeO*), the two rock classes are similar, suggesting that they are derived from a similar magmatic source. The Barnhill class, however, has higher abundances of Cl, Br, Zn, and Ge with comparable SO3 to the Irvine basalts. Nanophase ferric oxide (np ox) and volcanic glass were detected in the Barnhill class rocks by Mössbauer and Mini-TES, respectively, and imply greater alteration and cooling rates in the Barnhill than in the Irvine class rocks. The high volatile elements in the Barnhill class agree with volcanic textures that imply interaction with a briny groundwater during eruption and (or) by later alteration. Differences in composition between the Barnhill and Irvine classes allow the fingerprinting of a Na-Mg-Zn-Ge-Cl-Br (±Fe ± Ca ± CO2) brine with low S. Nearby sulfate salt soils of fumarolic origin may reflect fractionation of an acidic S-rich vapor during boiling of a hydrothermal brine at depth. Persistent groundwater was likely present during and after the formation of Home Plate

Atypical development of white matter microstructure of the corpus callosum in males with autism: a longitudinal investigation

Background: The corpus callosum is the largest white matter structure in the brain, and it is the most consistently reported to be atypical in diffusion tensor imaging studies of autism spectrum disorder. In individuals with typical development, the corpus callosum is known to undergo a protracted development from childhood through young adulthood. However, no study has longitudinally examined the developmental trajectory of corpus callosum in autism past early childhood. Methods: The present study used a cohort sequential design over 9 years to examine age-related changes of the corpus callosum in 100 males with autism and 56 age-matched males with typical development from early childhood (when autism can first be reliably diagnosed) to mid-adulthood (after development of the corpus callosum has been completed) (3 to 41 years of age). Results: The group with autism demonstrated a different developmental trajectory of white matter microstructure in the anterior corpus callosum’s (genu and body) fractional anisotropy, which suggests atypical brain maturation in these regions in autism. When analyses were broken down by age group, atypical developmental trajectories were present only in the youngest participants (10 years of age and younger). Significant main effects for group were found in terms of decreased fractional anisotropy across all three subregions of the corpus callosum (genu, body, and splenium) and increased mean diffusivity, radial diffusivity, and axial diffusivity in the posterior corpus callosum. Conclusions: These longitudinal results suggest atypical early childhood development of the corpus callosum microstructure in autism that transitions into sustained group differences in adolescence and adulthood. This pattern of results provides longitudinal evidence consistent with a growing number of published studies and hypotheses regarding abnormal brain connectivity across the life span in autism. Electronic supplementary material The online version of this article (doi:10.1186/s13229-015-0001-8) contains supplementary material, which is available to authorized users

Estimating Grizzly and Black Bear Population Abundance and Trend in Banff National Park Using Noninvasive Genetic Sampling

We evaluated the potential of two noninvasive genetic sampling methods, hair traps and bear rub surveys, to estimate population abundance and trend of grizzly (Ursus arctos) and black bear (U. americanus) populations in Banff National Park, Alberta, Canada. Using Huggins closed population mark-recapture models, we obtained the first precise abundance estimates for grizzly bears ( = 73.5, 95% CI = 64–94 in 2006;  = 50.4, 95% CI = 49–59 in 2008) and black bears ( = 62.6, 95% CI = 51–89 in 2006;  = 81.8, 95% CI = 72–102 in 2008) in the Bow Valley. Hair traps had high detection rates for female grizzlies, and male and female black bears, but extremely low detection rates for male grizzlies. Conversely, bear rubs had high detection rates for male and female grizzlies, but low rates for black bears. We estimated realized population growth rates, lambda, for grizzly bear males ( = 0.93, 95% CI = 0.74–1.17) and females ( = 0.90, 95% CI = 0.67–1.20) using Pradel open population models with three years of bear rub data. Lambda estimates are supported by abundance estimates from combined hair trap/bear rub closed population models and are consistent with a system that is likely driven by high levels of human-caused mortality. Our results suggest that bear rub surveys would provide an efficient and powerful means to inventory and monitor grizzly bear populations in the Central Canadian Rocky Mountains

Mycobacterium tuberculosis releases an antacid that remodels phagosomes

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