Abstract: Respiratory syncytial virus (RSV) infection may lead to severe respiratory illness in young children. Thus, there is a need for a live attenuated vaccine, which would mimic the natural course of infection without causing illness; however, restricting viral replication also reduces the immune response. Reported herein is a method of vaccination using a single dose of a recombinant RSV lacking the M2-2 protein that surprisingly induced a stronger immune response to RSV than previous vaccine candidates despite being more restricted in replication.

Abstract: Methods are disclosed for determining whether a subject has a synucleinopathy. Methods are also disclosed for detecting misfolded alpha synuclein (?Syn) in a biological sample or fraction thereof. These methods include the use of an ?Syn seeding assay.

Abstract: Disclosed are pharmaceutical formulations comprising a compound of formula (I): in which R1, R2, R3, and R4 are as described herein, or a pharmaceutically acceptable salt thereof. Also provided are methods for treating pancreatic adenocarcinoma comprising administration of a compound of formula (I), or a pharmaceutically acceptable salt thereof, and methods of detecting the change in expression levels of one or both of FoxA1 and FoxO6 in a pancreatic adenocarcinoma tumor sample from a mammal, wherein the mammal has been administered a compound of formula (I), or a pharmaceutically acceptable salt thereof.

Abstract: The present invention provides for novel methods for regulating and detecting the cytosine methylation status of DNA. The invention is based upon identification of a novel and surprising catalytic activity for the family of TET proteins, namely TET1, TET2, TET3, and CXXC4. The novel activity is related to the enzymes being capable of converting the cytosine nucleotide 5-methylcytosine into 5-hydroxymethylcytosine by hydroxylation.

Abstract: Disclosed herein are novel methods of treating pain in a patient in need thereof by providing to the patient a selective dopamine D3 receptor antagonist/partial agonist which when used with an opioid analgesic, can mitigate the development of opioid dependence, by preventing the need for dose escalation while either maintaining the opioid analgesic effect or providing analgesia with a lower dose of the opioid. In addition, the D3 antagonists/partial agonists described herein may be used to augment the effectiveness of current Medication Assisted Treatment regimens (e.g. methadone or buprenorphine) for the treatment of opioid use disorders.

Abstract: Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.

Abstract: Monoclonal antibodies that bind glypican-2 (GPC2) with high affinity are described. Immunotoxins and chimeric antigen receptors (CARs) that include the disclosed antibodies or antigen-binding fragments thereof are further described. In some instances, the antibody or antigen-binding fragment is humanized. The disclosed GPC2-specific antibodies and conjugates can be used, for example, for the diagnosis or treatment of GPC2-positive cancers, including neuroblastoma, medulloblastoma and retinoblastoma.

Abstract: The present disclosure describes the grafting of epitope residues from human PCSK9 to non-human PCSK9 or PCSK9 structural homologs and elimination of 9-mers oligopeptides that are found in human protein to reduce self-targeting response. Anti-genicity of the epitope-scaffold constructs was demonstrated toward anti-human PCSK9 antibodies. similar to wild type human PCSK9. It was shown that disclosed PCSK9 immunogens could significantly reduce LDL and cholesterol levels in immunized mice.

Abstract: Anti-EBV gH antibodies, anti-EBV gL antibodies, anti-EBV gH/gL antibodies, and compositions of matter useful for the detection, diagnosis, prevention, and treatment of Epstein Barr Virus infection in humans, and methods of using those compositions of matter for the same.

Abstract: Disclosed is a method of purifying extracellular vesicles in a sample comprising extracellular vesicles and molecules that are not bound to the extracellular vesicles. The method includes (a) providing a mixed mode resin composition containing a first resin having pores with a pore size that traps unbound molecules by at least by a size exclusion mechanism, and a second resin containing at least one affinity ligand; (b) contacting the sample with the mixed mode resin composition to trap at least a portion of the unbound molecules; and (c) separating the sample from the mixed mode resin composition and obtaining a sample containing extracellular vesicles at a higher concentration than prior to step (b). Further disclosed is a method of labeling an extracellular vesicle with a fluorophore that labels proteins which includes the use of a mixed mode resin composition.

Abstract: Cancer patients make antibodies to tumor-derived proteins that are potential biomarkers for early detection. Twenty-eight antigens have been identified as potential biomarkers for the early detection of basal-like breast cancer (Tables 1, 2). Also, a 13-AAb classifier has been developed that differentiate patients with BLBC from healthy controls with 33% sensitivity at 98% specificity (Table 3).

Abstract: A self-reinforcing composite gel includes a solvent, and a plurality of swellable crosslinked polymer particles dispersed in a crosslinked polymer matrix, wherein the crosslinked polymer matrix and the plurality of swellable crosslinked polymer particles are immersed in the solvent, wherein the swellable crosslinked polymer particles absorb more solvent at equilibrium than the matrix polymer, and wherein the plurality of swellable crosslinked polymer particles swell in the solvent and are present in an amount sufficient to maintain or increase the elastic modulus and/or load-bearing ability of the self-reinforcing composite gel, i.e., compared to that of the crosslinked matrix polymer alone, upon swelling in the solvent.

Abstract: A replication-competent adenovirus type 4 (Ad4) modified to express the SARS-COV-2 spike protein is described. The genome of the recombinant Ad4 is modified to have a deletion of at least a portion of the adenovirus E3 region to accommodate insertion of the spike protein coding sequence. Administration of the recombinant Ad4 to the upper respiratory tract elicits mucosal immunity, which is important for protection against SARS-COV-2 infection and for preventing transmission of the virus.

Abstract: The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., multiple myeloma). It relates to anti-CD56 antibodies, chimeric antigen receptors (CARs) that specifically target human CD56, and immunoresponsive cells comprising such CARs. The presently disclosed CD56-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

Abstract: The present invention relates to monoclonal antibodies for a spike protein of the Middle East respiratory syndrome coronavirus (MERS-CoV), and a use thereof. Particularly, monoclonal antibodies 77-A5, 77-A6, 90-A3, 90-A9, 90-B2, 90-B7, 90-C4, 90-E5, 90-E6, 90-F1 and 90-F2 according to the present invention have excellent attachment force with respect to a full-length spike protein of MERS-CoV and the S1 domain of the protein, and, of the monoclonal antibodies, the monoclonal antibodies 90-F1, 90-E5, 90-E6, 90-F2, 77-A5 and 77-A6 have excellent attachment force with respect to an RBD antigen of MERS-CoV. Also, the antibodies 77-A5, 77-A6, 90-E5, 90-E6, 90-F1 and 90-F2 exhibit neutralizing capacity with respect to a MERS pseudovirus and MERS-CoV, and the antibodies 90-B2 and 90-B7 exhibit neutralizing capacity only with respect to MERS-CoV. Further, the monoclonal antibodies have a particular monomeric form, and have excellent stability and thus may be useful for treating or diagnosing MERS.

Abstract: Disclosed are recombinant insect ferritin nanoparticles that can be used to display two different trimeric antigens at an equal ratio. Also disclosed are nucleic acids encoding the recombinant insect ferritin nanoparticles and methods of producing the recombinant insect ferritin nanoparticles. Methods for eliciting an immune response in a subject are also provided.

Abstract: Small molecule compounds that selectively bind to non-canonical G-quadruplex (G4) structures, such as G4s in DNA found in various types of genes described herein, along with methods of using the compounds to reduce or inhibit protein (e.g., N-Myc protein) expression in cells, such as cancer cells. The compounds have a structure according to formulas described herein, or a stereoisomer, tautomer, or pharmaceutically effective salt or ester thereof.

Abstract: A method of target enrichment or depletion from a sample with an analyte is described. A probe has one of a left-handed PNA pair and a targeting moiety, in which the left-handed PNA pair are a complementary pair of PNAs that are chiral and have a cyclic backbone modification that induces a left-handed helical structure. A capture surface has the other of the left-handed PNA pair; and the left-handed PNA pair bind to hybridize the probe to the capture surface, which may be a magnetic bead.

Abstract: Disclosed are live, chimeric non-human Mononegavirales vectors that allow a cell to express at least one protein from at least one human pathogen. In addition, compositions comprising the vectors, methods and kits for eliciting an immune response in a host, and methods of making the vectors are disclosed, in accordance with embodiments of the invention.

Abstract: Methods are disclosed for inhibiting a HIV infection in a subject. These methods include administering to the subject an effective amount of a recombinant gp120 protein comprising a deletion of HIV-1 Envelope residues 137-152 according to the HXBc2 numbering system, or a nucleic acid molecule encoding the recombinant gp120 protein, wherein the recombinant gp120 protein elicits an immune response to HIV-1. The methods also include administering to the subject an effective amount of a SAMT-247 microbicide.