Abstract: Non-liposome, non-micelle particles formed of a lipid, an additional adjuvant such as a TLR4 agonist, a sterol, and a saponin are provided. The particles are porous, cage-like nanoparticles, also referred to as nanocages, and are typically between about 30 nm and about 60 nm. In some embodiments, the nanocages include or are administered in combination with an antigen. The particles can increase immune responses and are particularly useful as adjuvants in vaccine applications and related methods of treatment. Preferred lipids, additional adjuvants including TLR4 agonists, sterols, and saponins, methods of making the nanocages, and method of using them are also provided.

Abstract: The present disclosure includes compositions and methods for detecting the presence of: a coronavirus or an immune response relevant to a coronavirus infection including T cells responsive to one or more coronavirus peptides or proteins comprising, consisting of, or consisting essentially of: one or more amino acid sequences selected from those sequences set forth in Table 2 (SEQ ID NOS: 1 to 292), Table 3 (SEQ ID NOS: 293 to 347), or both, or a subsequence, portion, homologue, variant or derivative thereof; a fusion protein; a pool of 2 or more peptides; or a polynucleotide that encodes one or more peptides or proteins, comprising, consisting of, or consisting essentially of one or more amino acid sequences set forth in Table 2 or Table 3, or a subsequence, portion, homologue, variant or derivative thereof. The disclosure further provides vaccines, diagnostics, therapies, and kits, comprising such proteins or peptides.

Abstract: The present invention includes compositions and methods for detecting the presence of: a coronavirus or an immune response to a coronavirus infection including T cells responsive to one or more coronavirus peptides or proteins comprising, consisting of, or consisting essentially of: one or more amino acid sequences selected from SEQ ID NO: 1 to 1126, subsequences, portions, homologues, variants or derivatives; a fusion protein comprising one or more amino acid sequences selected from SEQ ID NO: 1 to 1126; a pool of peptides or proteins selected from the amino acid sequences set forth in SEQ ID NO: 1 to 1126; or a polynucleotide that encodes one or more peptides or proteins, comprising, consisting of, or consisting essentially of an amino acid sequence selected from SEQ ID NO: 1 to 1126, subsequences, portions, homologues, variants or derivatives. The invention further provides vaccines, diagnostics, therapies, and kits, comprising such proteins or peptides.

Abstract: Immunization methods are provided. The methods typically include administering the subject an effective amount of an antigen and adjuvant to induce an immune response against an antigen, the method including two or more of (i) slow prime delivery of antigen and/or adjuvant, a (ii) temporally delayed 2nd immunization, and (iii) a robust adjuvant. Element (i) can be or include temporally extended exposure of antigen, adjuvant, or preferably the combination thereof, such as one or more of repeated administrations, infusion optionally by osmotic pump and escalating dosing. Element (ii) can include administering one or more boost doses of antigen and/or adjuvant, for example between 11 and 35 weeks after the start of the prime administration. A preferred robust adjuvant (iii) is one including non-liposome, non-micelle particles formed of a lipid, an additional adjuvant such as a TLR4 agonist, a sterol, and a saponin.

Abstract: Non-liposome, non-micelle particles formed of a lipid, an additional adjuvant such as a TLR4 agonist, a sterol, and a saponin are provided. The particles are porous, cage-like nanoparticles, also referred to as nanocages, and are typically between about 30 nm and about 60 nm. In some embodiments, the nanocages include or are administered in combination with an antigen. The particles can increase immune responses and are particularly useful as adjuvants in vaccine applications and related methods of treatment. Preferred lipids, additional adjuvants including TLR4 agonists, sterols, and saponins, methods of making the nanocages, and method of using them are also provided.

Abstract: Non-liposome, non-micelle particles formed of a lipid, an additional adjuvant such as a TLR4 agonist, a sterol, and a saponin are provided. The particles are porous, cage-like nanoparticles, also referred to as nanocages, and are typically between about 30 nm and about 60 nm. In some embodiments, the nanocages include or are administered in combination with an antigen. The particles can increase immune responses and are particularly useful as adjuvants in vaccine applications and related methods of treatment. Preferred lipids, additional adjuvants including TLR4 agonists, sterols, and saponins, methods of making the nanocages, and method of using them are also provided.

Abstract: The present disclosure relates to methods and compositions useful for initiating and propagating ICOS-mediated signaling. In particular, the present disclosure provides three peptide motifs which promote ICOS binding and whose ablation leads to modulated ICOS signaling and modulated signaling mediated by TBK1, IRF4, IKK?, or TBKBP1. The binding of these peptide motifs or the addition of such motifs as co-stimulatory agents leads to modulated immune responses, and provides new and unexpected therapies for neurodegenerative, autoimmune, metabolic, cancer inflammatory, or immunodeficiency conditions, diseases, or disorders.

Abstract: Recurrent tonsillitis disease (RT) is a common indication for pediatric tonsillectomy, the most frequent childhood surgery. It is unknown why some children develop RT. The present disclosure demonstrates that RT tonsils exhibit significantly smaller germinal centers than non-RT tonsils, concomitant with a bias against Group A Streptococcus (GAS)-specific germinal center follicular helper CD4+ T cells (GC Tfh), and significantly reduced antibodies to the GAS virulence factor SpeA. The present disclosure also shows a significant immunogenetic component to this disease, with the identification of ‘at risk’ and ‘protective’ HLA alleles for RT. Finally, the present disclosure identifies a new cell type, granzyme B+GC Tfh cells, which are activated by SpeA, are significantly more abundant in RT GC Tfh cells, and have the capacity to kill B cells, thus, providing a window into the immunology and genetics of a classic childhood disease and identifies a new type of pathogenic T cell.

Abstract: Non-liposome, non-micelle particles formed of a lipid, an additional adjuvant such as a TLR4 agonist, a sterol, and a saponin are provided. The particles are porous, cage-like nanoparticles, also referred to as nanocages, and are typically between about 30 nm and about 60 nm. In some embodiments, the nanocages include or are administered in combination with an antigen. The particles can increase immune responses and are particularly useful as adjuvants in vaccine applications and related methods of treatment. Preferred lipids, additional adjuvants including TLR4 agonists, sterols, and saponins, methods of making the nanocages, and method of using them are also provided.

Abstract: Recurrent tonsillitis disease (RT) is a common indication for pediatric tonsillectomy, the most frequent childhood surgery. It is unknown why some children develop RT. The present disclosure demonstrates that RT tonsils exhibit significantly smaller germinal centers than non-RT tonsils, concomitant with a bias against Group A Streptococcus (GAS)-specific germinal center follicular helper CD4+ T cells (GC Tfh), and significantly reduced antibodies to the GAS virulence factor SpeA. The present disclosure also shows a significant immunogenetic component to this disease, with the identification of ‘at risk’ and ‘protective’ HLA alleles for RT. Finally, the present disclosure identifies a new cell type, granzyme B+GC Tfh cells, which are activated by SpeA, are significantly more abundant in RT GC Tfh cells, and have the capacity to kill B cells, thus, providing a window into the immunology and genetics of a classic childhood disease and identifies a new type of pathogenic T cell.

Abstract: The present disclosure relates to methods and compositions useful for initiating and propagating ICOS-mediated signaling. In particular, the present disclosure provides three peptide motifs which promote ICOS binding and whose ablation leads to modulated ICOS signaling and modulated signaling mediated by TBK1, IRF4, IKK?, or TBKBP1. The binding of these peptide motifs or the addition of such motifs as co-stimulatory agents leads to modulated immune responses, and provides new and unexpected therapies for neurodegenerative, autoimmune, metabolic, cancer inflammatory, or immunodeficiency conditions, diseases, or disorders.

Abstract: Presented herein are methods of detecting and/or monitoring germinal center activity in a subject according to an amount of CXCL13 in the blood of a subject. Also presented herein are methods of determine the efficacy of a vaccine or antigen at inducing an immune response. Methods are also presented for monitoring, screening, and/or diagnosing an autoimmune disorder or immune-suppression in a subject and for monitoring or adjusting a treatment.

Abstract: The invention provides methods and uses for stimulating, inducing, increasing or enhancing Tfh (follicular helper) cell differentiation, germinal center B cell development or an antibody response, and an immune response by administering activin or a subsequence thereof, or an activator of activin receptor, in an amount effective to stimulate, induce, increase or enhance Tfh (follicular helper) cell differentiation, germinal center B cell development or an antibody response, and an immune response, respectively. Also provided are peptides comprising or consisting of a subsequence of human activin sequence, in which the activin sequence or subsequence stimulates, induces, increases or enhances development of Tfh (follicular helper) cell differentiation, germinal center B cell development, an antibody response, an immune response and/or an immune response induced by a vaccine.

Abstract: The invention relates to antibodies and subsequences thereof that specifically bind to poxvirus B5R envelope protein, antibodies and subsequences thereof that specifically bind to poxvirus H3L envelope protein, and combinations thereof.

Abstract: The invention relates to antibodies and subsequences thereof that specifically bind to poxvirus B5R envelope protein, antibodies and subsequences thereof that specifically bind to poxvirus H3L envelope protein, and combinations thereof.

Abstract: The invention relates to antibodies and subsequences thereof that specifically bind to poxvirus B5R envelope protein, antibodies and subsequences thereof that specifically bind to pox virus H3L envelope protein, and combinations thereof.

Abstract: The invention relates to, among other things, methods of protecting against poxvirus infection or pathogenesis and including pox viruses such as small pox (variola major and variola minor), cowpox, monkey pox vaccinia virus, and Molluscum Contagiosum using compositions such as human, humanized and chimeric antibodies that specifically bind to H3L protein.

Abstract: The present invention provides a population of live attenuated recombinant replication-competent viruses, which population comprises at least two member viruses, each of the member viruses comprising a nucleotide sequence encoding a different antigenic polypeptide from a source other than a parent virus from which the recombinant virus was derived. When a eukaryotic cell of a mammalian host is infected with a member of the population, the nucleotide sequence is expressed, the antigenic polypeptide is produced, and elicits an immune response. The invention further provides compositions, including immunogenic compositions, comprising a subject virus population. The invention further provides methods of eliciting an immune response to a polypeptide in an individual, involving administering a subject virus population. The invention further provides devices for use in eliciting an immune response.