Immunogenic RSV polypeptides
Inventors
Khurana, Surender • Golding, Hana
Assignees
US Department of Health and Human Services
Publication Number
US-11478542-B2
Publication Date
2022-10-25
Expiration Date
2036-02-18
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Abstract
This invention provides immunogenic compositions comprising an immune stimulant and an respiratory syncytial virus (RSV) oligopeptide or an unglycosylated RSV polypeptide. The RSV oligopeptides are shown in SEQ ID NO: 3-33. The unglycosylated RSV polypeptide may consist essentially of the ectodomain of an RSV G protein, such as that shown in SEQ ID NO: 2 or the ectodomain of an RSV F protein such as the ectodomain of the F protein shown in SEQ ID NO: 39.
Core Innovation
This invention provides immunogenic compositions comprising an immune stimulant combined with RSV oligopeptides or unglycosylated RSV polypeptides to induce protective immune responses against RSV infection. The RSV oligopeptides are specified by sequences SEQ ID NO: 3-33, which include peptides from the RSV F and G proteins. Unglycosylated RSV polypeptides typically consist essentially of the ectodomains of RSV G or F proteins, such as those approximately 95% identical to sequences SEQ ID NO: 2, 42, or 40, and are often produced recombinantly in prokaryotic cells.
The problem addressed centers around the challenges in developing effective RSV vaccines, which include the young age of the target population, recurrent infection despite previous exposure, and potential for disease enhancement observed historically with formaldehyde-inactivated RSV vaccines. Prior vaccines based on glycosylated RSV proteins have shown limited immunogenicity and safety concerns, such as enhanced respiratory disease and lung pathology triggered by Th2-biased immune responses. There remains a need for RSV vaccines that provide robust, protective immunity without inducing disease enhancement.
The invention shows that immunogenic compositions containing unglycosylated RSV G ectodomain or specific RSV oligopeptides combined with immune stimulants induce protective immunity in subjects, including infants, pregnant women, and the elderly. Experimental data demonstrate that unglycosylated RSV G protein expressed in bacteria elicits broader and stronger antibody responses and protection in mouse models against both homologous and heterologous RSV strains, without enhanced lung pathology or Th2 cytokine skewing that is seen with glycosylated counterparts. The compositions may include monomeric, multimeric, or oligopeptide forms combined with adjuvants or viral vectors serving as immune stimulants.
Claims Coverage
The claims of the patent include several inventive features encompassing immunogenic compositions comprising immune stimulants and RSV oligopeptides or multimeric polypeptides derived from RSV sequences, as well as methods for inducing immune responses using these compositions. The coverage highlights four main inventive features focused on the RSV oligopeptides, multimeric constructs, immune stimulation, and administration methods.
Immunogenic compositions comprising specific RSV oligopeptides with immune stimulants
Claims disclose immunogenic compositions comprising an immune stimulant and an RSV oligopeptide sequence selected from SEQ ID NO: 5, 7, 13, or 16, where the oligopeptide is less than 75 amino acids in length, and wherein the immune stimulant is present in an amount effective to induce an immune response against the RSV oligopeptide.
Multimeric polypeptides comprising multiple copies of RSV oligopeptides with immune stimulants
Claims cover immunogenic compositions comprising an immune stimulant and a multimeric polypeptide comprising more than one copy of one or more RSV oligopeptides represented by the sequences in claim 1. The multimeric polypeptide may comprise repeated sequences of the oligopeptides or combinations with other RSV or non-RSV viral oligopeptides, and the immune stimulant is present in an immunologically effective amount.
Inclusion of additional immunogens from RSV or other viruses
Claims include embodiments where compositions comprise a second immunogen in addition to the RSV oligopeptide(s). The second immunogen may be derived from RSV or a virus other than RSV, broadening the potential scope and protective breadth of the immunogenic compositions.
Methods for inducing immune responses using the immunogenic compositions
Claims provide methods of inducing an immune response against RSV infection in a subject by administering an immunologically effective amount of the claimed immunogenic compositions, typically by intramuscular injection, targeting subjects such as infants.
The claims comprehensively cover immunogenic compositions comprising specific RSV oligopeptides or their multimeric forms with immune stimulants, inclusion of additional immunogens, and methods for inducing protective immune responses in subjects, thereby protecting the compositions and uses of RSV oligopeptides for vaccination.
Stated Advantages
Unglycosylated RSV G ectodomain induces higher protective immunity than glycosylated forms, including stronger and broader antibody responses.
Compositions avoid vaccine-enhanced disease and lung pathology associated with prior glycosylated RSV G vaccines by not inducing Th2-skewed cytokine responses.
RSV oligopeptides and polypeptides produced in prokaryotic systems offer economical and safe vaccine alternatives with effective protection against homologous and heterologous RSV strains.
Documented Applications
Use of immunogenic compositions comprising RSV oligopeptides or unglycosylated RSV polypeptides to prevent or treat RSV infection in subjects including infants, pregnant mothers, women of childbearing age, and the elderly.
Use in methods for inducing protective immune responses against RSV infection by administering the immunogenic compositions, typically by intramuscular injection.
Use of RSV oligopeptides in diagnostic assays to detect immune responses against RSV by detecting antibody binding or cellular immune responses in biological samples from subjects.
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