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Publication Number
US-11260122-B2
Publication Date
2022-03-01
Expiration Date
Abstract
Methods for providing novel compositions useful as influenza immunogens are provided. The compositions enable a host response to immunogen sites normally not recognized by a host. The novel immunogens can be used as vaccines or to develop antibodies.
Core Innovation
The invention concerns influenza vaccine and immunogen compositions comprising an influenza hemagglutinin, or an antigenic portion thereof, including SEQ ID NO:69 or 70. The hemagglutinin antigenic portion is described in the context of immunodominant epitopes and immune refocusing, or immunodampening, to redirect a host response from immunodominant HA/NA epitopes toward subdominant or previously silent epitopes.
The disclosed concept is grounded in influenza immune dominance, including deceptive imprinting, original antigenic sin, and clonal dominance associated with class one versus class two pathogens. Immune refocusing is presented as an approach intended to improve breadth of influenza immunity rather than rely on conventional strain-mix practices. Engineered HA epitope muteins are described across immune epitopes labeled A to E within HA antigenic sites.
The document further describes influenza hemagglutinin and antigenic portions engineered using epitope mutein strategies that can include deletions, charged residue substitutions, and introduction or removal of N-linked glycosylation sequons. The resulting immune-refocused HA antigens are evaluated using hemagglutination inhibition and virus neutralization assays, and a ferret challenge model is referenced for nonclinical evaluation endpoints. Reported outcomes include increased heterologous reactivity and improved responses against divergent influenza strains, such as divergent H3N2 strains.
Claims Coverage
The independent claim covers a composition defined by the presence of an influenza hemagglutinin, or antigenic portion, comprising SEQ ID NO:69 or 70. Across the dependent claims, the inventive scope further specifies HA epitope sets and structural features and defines acceptable presentation formats and selected adjuvant classes, yielding multiple claim variants built around the same SEQ ID-defined immunogen.
Influenza hemagglutinin comprising SEQ ID NO:69 or 70
A composition comprising an influenza hemagglutinin, or antigenic portion thereof, comprising SEQ ID NO:69 or 70.
HA epitope sets A, B, C, D and/or E in the antigenic portion
The composition further includes HA epitope(s) labeled A, B, C, D and/or E in its antigenic portion.
Hemagglutinin subtype H1 or H3
The hemagglutinin is either subtype H1 or H3.
Added glycosylation site in the hemagglutinin or antigenic portion
The hemagglutinin or its antigenic portion includes an added glycosylation site.
Adjuvant as an aluminum salt or lipopolysaccharide
The adjuvant is an aluminum salt or a lipopolysaccharide.
Virus-like particle comprising the composition
The composition is incorporated into a virus-like particle (VLP).
Overall claim coverage centers on an influenza hemagglutinin, or antigenic portion, defined by SEQ ID NO:69 or 70, with dependent claim variants narrowing to HA epitope labeling A to E, HA subtypes H1 or H3, structural modulation via an added glycosylation site, and formulation options including aluminum salts or lipopolysaccharide adjuvants and presentation as a virus-like particle.
Stated Advantages
Broader cross-subtype and cross-strain immunity by redirecting host responses from immunodominant epitopes to subdominant or previously silent epitopes.
Reduced reliance on annual strain-mix production as described in the document’s motivation and background.
Documented Applications
Influenza vaccine and immunogen compositions incorporating immune refocusing or immunodampening strategies for redirected host immune responses.
Nonclinical evaluation of the immune-refocused influenza immunogens using hemagglutination inhibition and virus neutralization assays and a ferret challenge model.
Presentation of influenza immunogen constructs in virus-like particles (VLPs) as described in the document.
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