Development of an immunochromatographic lateral flow dipstick for the detection of Mycobacterium tuberculosis 16 kDa antigen (Mtb-strip)

Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium that causes tuberculosis (TB). This contagious disease remains a severe health problem in the world. The disease is transmitted via inhalation of airborne droplets carrying Mtb from TB patients. Early detection of the disease is vital to prevent transmission of the infection to people in close contact with the patients. To date, there is a need of a simple, rapid, sensitive and specific diagnostic test for TB. Previous studies showed the potential of Mtb 16 kDa antigen (Ag16) in TB diagnosis. In this study, lateral flow immunoassay, also called simple strip immunoassay or immunochromatographic test (ICT) for detection of Ag16 was developed (Mtb-strip) and assessed as a potential rapid TB diagnosis method. A monoclonal antibody against Ag16 was optimized as the capturing and detection antibody on the Mtb-strip. Parameters affecting the performance of the Mtb-strip were also optimized before a complete prototype was developed. Analytical sensitivity showed that Mtb-strip was capable to detect as low as 125 ng of purified Ag16. The analytical sensitivity of Mtb-strip suggests its potential usefulness in different clinical applications

Measurement of Total and Differential Cross Sections of Neutrino and Antineutrino Coherent π±\pi^\pm Production on Carbon

Neutrino induced coherent charged pion production on nuclei, $\overline{\nu}_\mu A\to\mu^\pm\pi^\mp A$, is a rare inelastic interaction in which the four-momentum squared transfered to the nucleus is nearly zero, leaving it intact. We identify such events in the scintillator of MINERvA by reconstructing |t| from the final state pion and muon momenta and by removing events with evidence of energetic nuclear recoil or production of other final state particles. We measure the total neutrino and antineutrino cross sections as a function of neutrino energy between 2 and 20 GeV and measure flux integrated differential cross sections as a function of $Q^2$, $E_\pi$ and $\theta_\pi$. The $Q^2$ dependence and equality of the neutrino and anti-neutrino cross-sections at finite $Q^2$ provide a confirmation of Adler's PCAC hypothesis

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

Cellular Immune Responses to Nine Mycobacterium tuberculosis Vaccine Candidates following Intranasal Vaccination

BACKGROUND: The identification of Mycobacterium tuberculosis vaccines that elicit a protective immune response in the lungs is important for the development of an effective vaccine against tuberculosis. METHODS AND PRINCIPAL FINDINGS: In this study, a comparison of intranasal (i.n.) and subcutaneous (s.c.) vaccination with the BCG vaccine demonstrated that a single moderate dose delivered intranasally induced a stronger and sustained M. tuberculosis-specific T-cell response in lung parenchyma and cervical lymph nodes of BALB/c mice than vaccine delivered subcutaneously. Both BCG and a multicomponent subunit vaccine composed of nine M. tuberculosis recombinant proteins induced strong antigen-specific T-cell responses in various local and peripheral immune compartments. Among the nine recombinant proteins evaluated, the alanine proline rich antigen (Apa, Rv1860) was highly antigenic following i.n. BCG and immunogenic after vaccination with a combination of the nine recombinant antigens. The Apa-induced responses included induction of both type 1 and type 2 cytokines in the lungs as evaluated by ELISPOT and a multiplexed microsphere-based cytokine immunoassay. Of importance, i.n. subunit vaccination with Apa imparted significant protection in the lungs and spleen of mice against M. tuberculosis challenge. Despite observed differences in the frequencies and location of specific cytokine secreting T cells both BCG vaccination routes afforded comparable levels of protection in our study. CONCLUSION AND SIGNIFICANCE: Overall, our findings support consideration and further evaluation of an intranasally targeted Apa-based vaccine to prevent tuberculosis

Seasonal Variation of Multiple-Muon Cosmic Ray Air Showers Observed in the NOvA Detector on the Surface

We report the rate of cosmic ray air showers with multiplicities exceeding 15 muon tracks recorded in the NOvA Far Detector between May 2016 and May 2018. The detector is located on the surface under an overburden of 3.6 meters water equivalent. We observe a seasonal dependence in the rate of multiple-muon showers, which varies in magnitude with multiplicity and zenith angle. During this period, the effective atmospheric temperature and surface pressure ranged between 210 K to 230 K and 940mbar to 990mbar, respectively; the shower rates are anti-correlated with the variation in the effective temperature. The variations are about 30% larger for the highest multiplicities than the lowest multiplicities and 20% larger for showers near the horizon than vertical showers

Measurement of the Double-Differential Muon-neutrino Charged-Current Inclusive Cross Section in the NOvA Near Detector

We report cross-section measurements of the final-state muon kinematics for \numu charged-current interactions in the NOvA near detector using an accumulated 8.09$\times10^{20}$ protons-on-target (POT) in the NuMI beam. We present the results as a double-differential cross section in the observed outgoing muon energy and angle, as well as single-differential cross sections in the derived neutrino energy, $E_\nu$, and square of the four-momentum transfer, $Q^2$. We compare the results to inclusive cross-section predictions from various neutrino event generators via $\chi^2$ calculations using a covariance matrix that accounts for bin-to-bin correlations of systematic uncertainties. These comparisons show a clear discrepancy between the data and each of the tested predictions at forward muon angle and low $Q^2$, indicating a missing suppression of the cross section in current neutrino-nucleus scattering models

Extended search for supernova-like neutrinos in NOvA coincident with LIGO/Virgo detections

A search is performed for supernova-like neutrino interactions coincident with 76 gravitational wave events detected by the LIGO/Virgo Collaboration. For 40 of these events, full readout of the time around the gravitational wave is available from the NOvA Far Detector. For these events, we set limits on the fluence of the sum of all neutrino flavors of $F < 7(4)\times 10^{10}\mathrm{cm}^{-2}$ at 90% C.L. assuming energy and time distributions corresponding to the Garching supernova models with masses 9.6(27)$\mathrm{M}_\odot$. Under the hypothesis that any given gravitational wave event was caused by a supernova, this corresponds to a distance of $r > 29(50)$kpc at 90% C.L. Weaker limits are set for other gravitational wave events with partial Far Detector data and/or Near Detector data.Comment: 10 pages, 2 figure

Supernova neutrino detection in NOvA

The NOvA long-baseline neutrino experiment uses a pair of large, segmented, liquid-scintillator calorimeters to study neutrino oscillations, using GeV-scale neutrinos from the Fermilab NuMI beam. These detectors are also sensitive to the flux of neutrinos which are emitted during a core-collapse supernova through inverse beta decay interactions on carbon at energies of O(10 MeV). This signature provides a means to study the dominant mode of energy release for a core-collapse supernova occurring in our galaxy. We describe the data-driven software trigger system developed and employed by the NOvA experiment to identify and record neutrino data from nearby galactic supernovae. This technique has been used by NOvA to self-trigger on potential core-collapse supernovae in our galaxy, with an estimated sensitivity reaching out to 10 kpc distance while achieving a detection efficiency of 23% to 49% for supernovae from progenitor stars with masses of 9.6 M_⊙ to 27 M_⊙, respectively