Patent classifications
C12N2760/18523
Prefusion RSV F proteins and their use
- Peter Kwong ,
- Barney Graham ,
- John Mascola ,
- Li Ou ,
- Aliaksandr Druz ,
- Man Chen ,
- Wing-pui Kong ,
- Ivelin Stefanov Georgiev ,
- Emily Rundlet ,
- Michael Gordon Joyce ,
- Yaroslav Tsybovsky ,
- Paul Thomas ,
- Marie Pancera ,
- Mallika Sastry ,
- Cinque Soto ,
- Joseph Van Galen ,
- Guillaume Stewart-Jones ,
- Yongping Yang ,
- Baoshan Zhang ,
- Ulrich Baxa
Embodiments of a recombinant Respiratory Syncytial Virus (RSV) F ectodomain trimer stabilized in a prefusion conformation are provided. Also disclosed are nucleic acids encoding the RSV F ectodomain trimer and methods of producing the RSV F ectodomain trimer. Methods for inducing an immune response in a subject are also disclosed. In some embodiments, the method can be a method for treating or preventing a RSV infection in a subject by administering a therapeutically effective amount of the recombinant RSV F ectodomain trimer to the subject.
MULTIVALENT VACCINE FOR PARAMYXOVIRUSES AND USES THEREOF
Provided are compositions pharmaceutical compositions, comprising two or more virus-like particles (VLPs), wherein a first virus-like particle (VLP) comprises a first component comprising a respiratory syntactical virus (RSV) F protein ectodomain or antigenic variant thereof; and a second virus-like particle (VLP) comprises a first component comprising a comprises a human metapneumovirus (hMPV) F protein ectodomain or antigenic variant thereof. Further provided are methods of using said compositions for vaccination.
RSV virus-like particles and methods of use thereof
The present disclosure relates to virus-like particles and vaccine compositions for inducing immunity and preventing respiratory syncytial virus (RSV) infection. Specifically, the disclosure provides virus like-particles (VLPs) for use in inducing immunity to respiratory syncytial virus (RSV) infections or symptoms thereof, wherein the VLP comprising a respiratory RSV matrix protein (M) and an RSV M2-1 protein, a glycoprotein (G), a fusion protein (F), and/or a phosphoprotein (P).
Modified RSV F proteins and methods of their use
The present invention is generally related to modified or mutated respiratory syncytial virus fusion (F) proteins and methods for making and using them, including immunogenic compositions such as vaccines for the treatment and/or prevention of RSV infection.
Vaccine composition
The present invention relates to vaccine compositions, most notably vaccine compositions wherein the antigenic component is large, for example over 50 kDa, or multimeric, i.e. comprised of subunits. Such antigenic components are of particular interest, because they may represent antigenic components from pathogens that currently it is not possible to vaccinate against. The invention relates to a composition comprising a particle displaying an antigenic component, wherein said composition comprises an antigenic component comprising a first peptide tag, and a moiety comprising a second peptide tag, wherein the antigenic component and the moiety are linked via an isopeptide bond between said first and second peptide tags, and wherein the antigenic component is over 50 kDa, or alternatively is multimeric.
Lipopeptide building blocks and synthetic virus-like particles
The present invention relates to a lipopeptide building block consisting of (i) a peptide moiety comprising a coiled coil peptide chain segment, wherein said coiled coil peptide chain segment comprises 3 to 8 repeat units, and wherein said repeat unit consists of the sequence IEKKIE-X0 (SEQ ID NO:58), wherein X0 represents an amino acid; and (ii) a lipid moiety comprising the formula LM-I ##STR00001##
wherein R.sup.1 and R.sup.2 are independently C.sub.11-15 alkyl, wherein R.sup.3 is hydrogen or C(O)C.sub.11-15 alkyl wherein said lipid moiety is linked to said peptide moiety, wherein the wavy line in formula LM-I indicates the linkage site to said peptide moiety, as well as conjugates comprising said lipopeptide building blocks to which antigens are coupled, bundles of such conjugates, synthetic virus-like particles (SVLPs) comprising at least one bundle of conjugates and pharmaceutical compositions comprising the same.
PREFUSION RSV F PROTEINS AND THEIR USE
- Peter Kwong ,
- Barney Graham ,
- John Mascola ,
- Li Ou ,
- Aliaksandr Druz ,
- Man Chen ,
- Wing-pui Kong ,
- Ivelin Stefanov Georgiev ,
- Emily Rundlet ,
- Michael Gordon Joyce ,
- Yaroslav Tsybovsky ,
- Paul Thomas ,
- Marie Pancera ,
- Mallika Sastry ,
- Cinque Soto ,
- Joseph Van Galen ,
- Guillaume Stewart-Jones ,
- Yongping Yang ,
- Baoshan Zhang ,
- Ulrich Baxa
Embodiments of a recombinant Respiratory Syncytial Virus (RSV) F ectodomain trimer stabilized in a prefusion conformation are provided. Also disclosed are nucleic acids encoding the RSV F ectodomain trimer and methods of producing the RSV F ectodomain trimer. Methods for inducing an immune response in a subject are also disclosed. In some embodiments, the method can be a method for treating or preventing a RSV infection in a subject by administering a therapeutically effective amount of the recombinant RSV F ectodomain trimer to the subject.
VACCINE COMPOSITION
The present invention relates to vaccine compositions, most notably vaccine compositions wherein the antigenic component is large, for example over 50 kDa, or multimeric, i.e. comprised of subunits. Such antigenic components are of particular interest, because they may represent antigenic components from pathogens that currently it is not possible to vaccinate against. The invention relates to a composition comprising a particle displaying an antigenic component, wherein said composition comprises an antigenic component comprising a first peptide tag, and a moiety comprising a second peptide tag, wherein the antigenic component and the moiety are linked via an isopeptide bond between said first and second peptide tags, and wherein the antigenic component is over 50 kDa, or alternatively is multimeric.
Chimeric RSV and HMPV F proteins, immunogenic compositions, and methods of use
This disclosure describes a chimeric respiratory syncytial virus encoding a chimeric RSV and hMPV F protein and uses of the chimeric virus or components therein in a vaccine. In certain embodiments, this disclosure describes a live attenuated vaccine comprising an RSV backbone substituting the F proteins of RSV, for a chimeric RSV and hMPV F protein.
MUTANT OF RSV F PROTEIN
Disclosed is a mutant of a wild-type RSV F protein. The binding experiment of a pre-fusion conformation trimer-specific monoclonal antibody AM14 shows that the mutant provided in embodiments can have strong activity of binding to the AM14 monoclonal antibody, while the wild-type RSV F protein before artificial mutation has no activity of binding to the AM14 monoclonal antibody. The accelerated stability test result shows that the activity of binding of the mutant provided in the embodiments when placed in a 37 C. environment for four weeks to the AM14 monoclonal antibody does not change obviously. The animal immune experiment result shows that compared with the wild-type RSV F protein before artificial mutation, the mutant provided in the embodiments can induce production of a neutralizing antibody having a higher titer.