The Uab Research Foundation (the University of Alabama at Birmingham)

The University of Tokyo

David E Briles

Janet L Yother

Susan K Hollingshead

Larry S McDaniel

Hiroshi Kiyono

Alexis Brooks-Walter

Robert S Becker

Hong-Yin Wu

Masafumi Yamamoto

Edwin Swiatlo

Yoshikazu Yuki

Marilyn J Crain

Kristopher Genschmer

Reshmi Mukerji

Robert Kneller

Rebecca Tart

James M Watt

Frederik W Van Ginkel

The present embodiments provide compositions and methods related to novel recombinant protein immunogens, comprising specific portions of alpha helical domains (aHD) and proline rich regions (PRD) of pneumococcal surface protein A (PspA), which portions are linked to provide aHD-PRD constructs. The aHD and PRD proteins constituting the aHD-PRD constructs are selected to maximize cross-reactivity and provide protection against a broad spectrum of pneumococcal serotypes. Immunogenic compositions, including vaccines, comprising at least one aHD PRD construct may also include a non-linked aHD portion. Also provided are recombinant nucleic acid molecules that encode aHD-PRD constructs, vectors and recombinant host cells containing such molecules, aHD-PRD expression products, use of such nucleic acid molecules to express aHD-PRD constructs by recombinant techniques, and use of the expression products to elicit an immune or protective response against pneumococcal disease in a suitable host.

Pneumococcal vaccine combining selected alpha helical domains and proline rich domains of pneumococcal surface protein A

Provided herein are compositions designed to reduce or prevent bacterial infections (for example pneuomococcal infections), nasal carriage, nasal colonization, and central nervous system invasion. Provided herein is a composition comprising a pneumococcal neuraminidase, phosphocholine, pneumococcal teichoic acid, pneumococcal lipoteichoic acid, or an antigenic portion of either neuraminidase, phosphocholine, pneumococcal teichoic acid, pneumococcal lipoteichoic acid. Optionally, the composition can comprise any combination of a pneumococcal neuraminidase, a phosphocholine, a pneumococcal teichoic acid, a pneumococcal lipoteichoic acid or an antigenic portion of any one of these. Optionally the agents are detoxified. Further provided are methods of making and using the compositions disclosed herein. Specifically provided are methods of generating antibodies in a subject comprising administering to the subject an agent or composition taught herein. Also provided are methods of reducing or preventing nasal carriage or pneumococcal infection in a subject comprising administering to the subject a composition taught herein.

Compositions for reducing bacterial carriage and CNS invasion and methods of using same

Provided herein are compositions designed to reduce or prevent bacterial infections (for example pneuomococcal infections), nasal carriage, nasal colonization, and central nervous system invasion. Provided herein is a composition comprising a polypeptide comprising the amino acid sequence of SEQ ID NO:19 or a variant thereof that can elicit an anti-neuraminidase immune response. Further provided are methods of making and using the compositions disclosed herein. Specifically provided are methods of generating antibodies in a subject comprising administering to the subject an agent or composition taught herein. Also provided are methods of reducing or preventing nasal carriage or pneumococcal infection in a subject comprising administering to the subject a composition taught herein.

Detoxified pneumococcal neuraminidase and uses thereof

The embodiments described herein provide for immunogenic portions ofsurface protein A and surface protein C lacking alpha helical structure.

Non-coiled protective regions of pneumococcal surface proteins PspA and PspC

Provided herein are compositions designed to reduce or prevent pneuomococcal infections, nasal carriage, nasal colonization, and central nervous system invasion. Provided herein is a composition comprising a polypeptide comprising the amino acid sequence of SEQ ID NO: 19 or a variant thereof that can elicit an anti-neuraminidase immune response. Further provided are methods of making and using the compositions disclosed herein. Specifically provided are methods of generating antibodies in a subject comprising administering to the subject an agent or composition taught herein. Also provided are methods of reducing or preventing nasal carriage or pneumococcal infection in a subject comprising administering to the subject a composition taught herein.

Compositions and methods for eliciting an immune response againstare described. More particularly, the present disclosure relates to immunogenic PcpA polypeptides, including fragments of PcpA and variants thereof, and nucleic acids that encode the polypeptides. The present disclosure further relates to methods of making and using the immunogenic polypeptides. Further provided is a method of diagnosing pneumococcal infection (e.g., pneumonia) in a subject by obtaining a biological sample from the subject and detecting one or more pneumococcal antigens that are selectively expressed during invasion (e.g., PcpA or fragments thereof).

Diagnosing pneumococcal pneumonia

The present invention relates to vaccine composition(s) comprising at least two PspAs from strains selected from at least one family, the family being defined by PspAs from strains belonging to the family having greater than or equal to 50% homology in aligned sequences of a C-terminal region of an alpha helical region of PspA. Additionally, the families are further comprised of clades, wherein PspAs from strains which belong to a clade exhibit greater than 75% sequence homology in aligned sequences of the C-terminal region of the alpha helix of PspA. Vaccine compositions of the present invention preferably comprise a minimum of 4 and a maximum of 6 strains representing a single clade each, and the at least two PspAs are optionally serologically or broadly cross-reactive.

Strain selection of pneumococcal surface proteins

Disclosed and claimed are: epitopic regions of Pneumococcal Surface Protein C or 'PspC', different clades of PspC, isolated and/or purified nucleic acid molecules such as DNA encoding a fragment or portion of PspC such as an epitopic region of PspC or at least one epitope of PspC, uses for such nucleic acid molecules, e.g., to detect the presence of PspC or ofby detecting a nucleic acid molecule therefor in a sample such as by amplification and/or a polymerase chain reaction, vectors or plasmids which contain and/or express such nucleic acid molecles, e.g., in vitro or in vivo, immunological, immunogenic or vaccine compositions including at least one PspC and/or a portion thereof (such as at least one epitopic region of at least one PspC and/or at least one polypeptide encoding at least one epitope of at least one PspC), either alone or in further combination with at least one second pneumococcal antigen, such as at least one different PspC and/or a fragment thereof and/or at least one PspA and/or at least one epitopic region of at least one PspA and/or at least one polypeptide including at least one epitope of PspA. PspC or a fragment thereof, and thus a composition including PspC or a fragment thereof, can be administered by the same routes, and in approximately the same amounts, as PspA. Thus, the invention further provides methods for administering PspC or a fragment thereof, as well as uses of PspC or a fragment thereof to formulate such compositions.

Pneumococcal surface protein C (PspC), epitopic regions and strain selection thereof, and uses therefor

The present invention relates to vaccine composition(s) comprising at least two PspAs from strains selected from at least one family, the family being defined by PspAs from strains belonging to the family having greater than or equal to 50% homology in aligned sequences of a C-terminal region of an alpha helical region of PspA. Additionally, the families are further comprised of clades, wherein PspAs from strains which belong to a clade exhibit at least 75% sequence homology in aligned sequences of the C-terminal region of the alpha helix of PspA. Vaccine compositions of the present invention preferably comprise a minimum of 4 and a maximum of 6 strains representing a single clade each, and the at least two PspAs are optionally serologically or broadly cross-reactive.

PspAs, portions thereof, DNA therefor, and immunological compositions, primers and probes based thereon are disclosed claimed.

Pneumococcal genes, portions thereof, expression products therefrom, and uses of such genes, portions and products

The present invention relates to pneumococcal genes, portions thereof, expression products therefrom and uses of such genes, portions and products; especially to genes of e.g., the gene encoding pneumococcal surface protein A (PspA), i.e., the pspA gene, the gene encoding pneumococcal surface protein A-like proteins, such as pspA-like genes, e.g., the gene encoding pneumococcal surface protein C (PspC), i.e., the pspC gene, portions of such genes, expression products therefrom, and the uses of such genes, portions thereof and expression products therefrom.

Pneumococcal surface proteins and uses thereof

Oral or peroral administration, including intragastrically, of killed whole pneumococci, lysate of pneumococci and isolated and purified PspA, as well as immunogenic fragments thereof, particularly when administered with an adjuvant such as cholera toxin provides protection in a host, animal or human, against pneumococcal infection, including colonization, and systemic infection, such as sepsis. The ability to elicit protection against pneumococcal colonization in a host prevents carriage among immunized individuals, which can lead to elimination of disease from the population as a whole.

Oral administration of pneumoccal antigens

Oral administration of pneumococcal antigens

Mucosal administration, particularly intranasally, of killed whole pneumococci, lysate of pneumococci and isolated and purified PspA, as well as immunogenic fragments thereof, particularly when administered with cholera toxin B subunit, provides protection in animals against pneumococcal colonization and systemic infection. The ability to elicit protection against pneumococcal colonization in a host prevents carriage among immunized individuals, which can lead to elimination of disease from the population as a whole.

Growing community of inventors

Birmingham, AL, United States of America

David E Briles