Anti-RSV immunogens and methods of immunization
Inventors
Anderson, Larry J. • Haynes, Lia M. • Tripp, Ralph A.
Assignees
University of Georgia Research Foundation Inc UGARF • Centers of Disease Control and Prevention CDC • US Department of Health and Human Services
Publication Number
US-8771706-B2
Publication Date
2014-07-08
Expiration Date
2030-08-04
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Abstract
Immunogenic polypeptides corresponding to one or more RSV G glycoproteins, or analogs thereof, are provided as components of vaccines. The inventive compositions are useful as both a prophylactic and therapeutic for the prevention and treatment of RSV infections and associated pulmonary or other diseases. The inventive immunogens include regions of the RSV G protein, specifically, amino acid residues 164-176 of RSV G A2 protein or analogs thereof. This inventive immunogen is operable alone or in combination with other polypeptides such as the RSV G protein amino acid residues 155-206, or other vaccines such as live RSV vaccines, or inactivated RSV vaccines or immunogenic analogs thereof.
Core Innovation
The invention relates to immunogenic polypeptides corresponding to one or more respiratory syncytial virus (RSV) G glycoproteins or analogues thereof, provided as components of vaccines. These compositions serve both as prophylactic and therapeutic agents for preventing and treating RSV infections and associated pulmonary or other diseases. The immunogens specifically include regions of the RSV G protein, notably amino acid residues 164-176 of RSV G A2 protein or analogs thereof, usable alone or in combination with other polypeptides such as residues 155-206 of the RSV G protein or other RSV vaccine components.
RSV is a major cause of serious lower respiratory illness in infants, young children, elderly, and immune-compromised patients, with incomplete natural immunity leading to repeat infections. Despite numerous prior vaccine candidates, there is no safe and effective vaccine available, and treatments such as anti-RSV F protein antibodies (e.g., palivizumab) and antivirals like ribavirin have limited efficacy, especially in treating active infection. Additionally, RSV-induced host inflammatory responses contribute to disease pathogenesis, and current treatments inadequately address this aspect.
Efforts focusing mainly on the RSV F glycoprotein have not resulted in an effective vaccine, and prior formalin-inactivated RSV vaccines caused enhanced disease upon later infection. The RSV G protein influences host immune responses and may modulate disease severity. The invention addresses the need for a safe and effective RSV vaccine by selecting specific regions of the RSV G glycoprotein that elicit an immune response conferring protection and mitigating undesirable immunological reactions.
Claims Coverage
The patent presents two independent claims relating to RSV vaccines comprising isolated immunogens derived from RSV G protein sequences with protective immune responses and safety against enhanced RSV responses. The claims emphasize polypeptides corresponding to specific amino acid sequences and their immunogenicity.
RSV vaccine comprising isolated immunogens from specific RSV G protein regions
An RSV vaccine including an isolated immunogen consisting of amino acid sequences from positions 163 to 190 and/or 155 to 206 of SEQ ID NOs: 1, 7, or 8, or a combination thereof, capable of eliciting a protective immune response against RSV vaccine-enhanced immune responses.
Incorporation of isolation tags in immunogens
The immunogen can further include a tag suitable for isolation of the immunogen, facilitating its purification and use.
Multi-component vaccines using specific polypeptides of RSV G protein
Vaccines consisting of specific polypeptides such as SEQ ID NO: 4 or 5, optionally combined with a second immunogen from SEQ ID NO: 3 or 6, to enhance protective immune responses.
Use of immunogenic carriers coupled to RSV G protein immunogens
An RSV vaccine comprising isolated immunogens of the specified amino acid regions coupled to immunogenic carriers that promote the immunogenicity of the immunogen, enhancing vaccine efficacy.
The independent claims cover RSV vaccines featuring isolated immunogens from defined RSV G protein segments with protective immune effects and improved safety profiles, including the use of tags for isolation, multi-component formulations, and conjugation to immunogenic carriers to enhance immunogenicity.
Stated Advantages
The invention results in effective and protective immune responses against RSV while avoiding the enhanced disease associated with prior formalin-inactivated RSV vaccines.
Induction of antibodies that block detrimental RSV G protein biological activity and reduce pulmonary eosinophilia, leading to improved safety and reduced disease severity.
Broad-based protection due to use of conserved regions across RSV strains, including group A and B.
Documented Applications
Prophylactic vaccines for preventing RSV infections in humans and animals.
Therapeutic vaccines for treating active RSV infection and associated pulmonary diseases.
Use as vaccine components alone or in combination with live RSV vaccines, inactivated RSV vaccines, or other immunogenic analogs.
Vaccines administered to improve safety and efficacy of other RSV vaccines by mitigating enhanced immunopathology.
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