Sub-Nucleocapsid Nanoparticles: A Nasal Vaccine against Respiratory Syncytial Virus

Background: Bronchiolitis caused by the respiratory syncytial virus (RSV) in infants less than two years old is a growing public health concern worldwide, and there is currently no safe and effective vaccine. A major component of RSV nucleocapsid, the nucleoprotein (N), has been so far poorly explored as a potential vaccine antigen, even though it is a target of protective anti-viral T cell responses and is remarkably conserved between human RSV A and B serotypes. We recently reported a method to produce recombinant N assembling in homogenous rings composed of 10–11 N subunits enclosing a bacterial RNA. These nanoparticles were named sub-nucleocapsid ring structure (N SRS). Methodology and Principal Findings: The vaccine potential of N SRS was evaluated in a well-characterized and widely acknowledged mouse model of RSV infection. BALB/c adult mice were immunized intranasally with N SRS adjuvanted with the detoxified E. coli enterotoxin LT(R192G). Upon RSV challenge, vaccinated mice were largely protected against virus replication in the lungs, with a mild inflammatory lymphocytic and neutrophilic reaction in their airways. Mucosal immunization with N SRS elicited strong local and systemic immunity characterized by high titers of IgG1, IgG2a and IgA anti-N antibodies, antigen-specific CD8+ T cells and IFN-c-producing CD4+ T cells. Conclusions/Significance: This is the first report of using nanoparticles formed by the recombinant nucleocapsid protein as an efficient and safe intra-nasal vaccine against RSV

Nucleoprotein Nanostructures Combined with Adjuvants Adapted to the Neonatal Immune Context: A Candidate Mucosal RSV Vaccine

BACKGROUND: The human respiratory syncytial virus (hRSV) is the leading cause of severe bronchiolitis in infants worldwide. The most severe RSV diseases occur between 2 and 6 months-of-age, so pediatric vaccination will have to be started within the first weeks after birth, when the immune system is prone to Th2 responses that may turn deleterious upon exposure to the virus. So far, the high risk to prime for immunopathological responses in infants has hampered the development of vaccine. In the present study we investigated the safety and efficacy of ring-nanostructures formed by the recombinant nucleoprotein N of hRSV (N(SRS)) as a mucosal vaccine candidate against RSV in BALB/c neonates, which are highly sensitive to immunopathological Th2 imprinting. METHODOLOGY AND PRINCIPAL FINDINGS: A single intranasal administration of N(SRS) with detoxified E. coli enterotoxin LT(R192G) to 5-7 day old neonates provided a significant reduction of the viral load after an RSV challenge at five weeks of age. However, neonatal vaccination also generated an enhanced lung infiltration by neutrophils and eosinophils following the RSV challenge. Analysis of antibody subclasses and cytokines produced after an RSV challenge or a boost administration of the vaccine suggested that neonatal vaccination induced a Th2 biased local immune memory. This Th2 bias and the eosinophilic reaction could be prevented by adding CpG to the vaccine formulation, which, however did not prevent pulmonary inflammation and neutrophil infiltration upon viral challenge. CONCLUSIONS/SIGNIFICANCE: In conclusion, protective vaccination against RSV can be achieved in neonates but requires an appropriate combination of adjuvants to prevent harmful Th2 imprinting

Spectroscopic and photometric observations of the selected Algol-type binaries -II. V2080 Cygni and V2365 Ophiuchi

WOS: 000253312300024This paper is the second in the planned series of investigations. We present new radial velocities and photometric observations of V2080 Cyg and V2365 Oph. New UBV photometric data and radial velocities were analysed for the systems' parameters. While V2080 Cyg consists of two nearly equal F-type main-sequence stars, V2365 Oph has two different components, namely an early A-type primary and a G-type secondary star. New ephemerides are calculated for both systems. The masses of the component stars have been derived as 1.19 +/- 0.02 and 1.16 +/- 0.02 M(circle dot) for V2080 Cyg and 1.97 +/- 0.02 and 1.06 +/- 0.01 M(circle dot) for V2365 Oph. The effective temperatures and reddening of the systems have been estimated from Johnson wide-band UBV photometric calibrations. The radii have been measured by simultaneous fitting the UBV light curves using Wilson - Devinney code and are 1.60 +/- 0.01 R(circle dot) for both components of V2080 Cyg and 2.19 +/- 0.01 and 0.934 +/- 0.004 R(circle dot) for V2365 Oph. The absolute parameters of the stars in both systems lie within the same ranges in the mass-radius, mass-effective temperature, mass-luminosity and luminosity-effective temperature planes as in detached Algol systems. A comparison between the properties of the systems of interest and the predictions of theoretical evolutionary models is undertaken in the log g - logT(eff), log R - logM and radius-log age diagrams. The model predictions match the measured properties of V2080 Cyg for an age of about 5.6 Gyr and a 'solar' metal abundance (Z=0.019), indicating the components near the end of their core hydrogen-burning phases. However, the position of the components of V2365 Oph on the Hertzsprung - Russell (HR) diagram is best reproduced with evolutionary models for somewhat metal-deficient (Z=0.004) stars. We found an age of about 700 Myr, with the primary component slightly evolved off the zero-age main-sequence and the secondary one still very close to it. From the basic stellar parameters we have also redetermined the distances to V2080 Cyg and V2365 Oph as 78 1 and 251 8 pc, which are in agreement with, and more accurate than, Hipparcos values. The observations show that at least one of the components of V2365 Oph is an intrinsic variable with a period and peak-to-peak amplitude of 0.07 d and 0.05 mag, respectively. In accordance with its position in the HR diagram, the primary component should be considered as a delta Scuti star and it is believed to be the variable star in the system

Spectroscopic and photometric observations of selected Algol-type binaries - I. V1665 Aquilae and AG Arietis

WOS: 000250010200010We present the first radial velocities and ground-based photometric observations of V1665 Aql and AG Ari. These double-lined eclipsing binaries have eccentric orbits with eccentricities of 0.24 and 0.09, respectively. New UBV photometric data and radial velocities were analysed using a modified version of the Wilson-Devinney program for the parameters of the systems. Good phase coverage and relatively small scatter both in the light and in the radial-velocity curves meant that the eccentricity and the argument of periastron as well as orbital and stellar parameters could be determined. Our solutions indicate that AG Ari includes a third light with a considerable amount of 5.6 per cent in U, 6.4 per cent in B, and 9 per cent in V. By comparing its light contribution with the total light we classified it as an F-type star. The components in each system are of very nearly equal mass, temperature, and luminosity. Their absolute parameters were compared with those of stars belonging to well-studied detached eclipsing binaries. The components lie well inside the main-sequence band. In addition, the apsidal motion rates of the system have been determined from an analysis of all the photometric observations obtained by space missions and by us. We determined the preliminary apsidal motion periods of the systems to be 449 +/- 34 yr for V1665 Aql and 155 +/- 6 yr for AG Ari. Because well-detached eclipsing binaries are optimal distance indicators, we estimated the distances to V1665 Aql and AG Ari to be 477 +/- 40 and 292 +/- 18 pc from the determined absolute visual magnitudes and interstellar extinction. A comparison with evolutionary tracks indicates that the primary component of V1665 Aql has an age of about 1.6 x 10(8) yr and is near the main-sequence terminal age. The components of AG Ari are intermediate-mass main-sequence stars with an age of about 5.6 x 10(8) yr

Spectroscopic and photometric observations of the selected Algol-type binaries*-IV. V799 Cassiopeiae, BX Piscium and HD 172189

WOS: 000261982100019We present new radial velocities and UBV photometric observations of three eclipsing binaries, V799 Cas, BX Psc and HD 172189, in order to increase the number of close binaries with absolute parameters determined accurately. Standard wide-band indices for the systems and comparison stars were determined accurately. Using the times of mid-eclipses, new ephemerides are calculated for three systems. V799 Cas and HD 172189 consist of two well-detached components in eccentric orbits. BX Psc is a single-lined eclipsing binary which consists of a late-A and an early-K star. The effective temperatures of the hotter components and reddening of the systems have been estimated from Johnson wide-band UBV photometric calibrations. The UBV photometric data and radial velocities were analysed simultaneously for the systems' parameters using Wilson-Devinney code. The masses have been found to be 3.08 +/- 0.40, 2.97 +/- 0.40; 1.85 +/- 0.14, 0.80 +/-0.08; 2.06 +/- 0.15, 1.87 +/- 0.14 M(circle dot) for the primary and secondary stars of V799 Cas, BX Psc and HD 172189, respectively. The radii of the components are derived in the case of V799 Cas: 3.23 +/- 0.14, 3.20 +/- 0.14; in those of BX Psc: 3.76 +/- 0.14, 2.18 +/- 0.09; and HD 172189: 4.01 +/- 0.09, 2.97 +/- 0.07 R(circle dot). We have calculated the distances to the systems of V799 Cas, BX Psc and HD 172189 as 607 +/- 35, 213 +/- 6 and 432 +/- 12 pc, respectively, using bolometric magnitudes and empirical bolometric corrections for the component stars. The model predictions match the measured properties of V779 Cas, BX Psc and HD 172189 for an age of 250 Myr, 1 Gyr and 890 Myr, respectively. A subsolar fractional metal abundance, Z approximate to 0.008, provides a better match to the absolute parameters of all three systems.Turkish Scientific and Technological Research CouncilTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [105T276]The authors acknowledge generous allotment of observing time at Ege University Observatory, CAO and TUG of Turkey and David Dunlap Observatory, Canada (especially for Dr S. Rucinski). We also wish to thank the Turkish Scientific and Technological Research Council for supporting this work through grant no. 105T276. This research has made use of ADS-CDS data base, operated at the CDS, Strasbourgh, France. We are also grateful to Dr Herman Hensberge, whose comments helped to improve this paper