Multivalent live-attenuated influenza vaccine for prevention and control of equine influenza virus (EIV) in horses
Inventors
Martinez-Sobrido, Luis • Chambers, Thomas • King, Kendall Wayne
Assignees
University of Kentucky Research Foundation • University of Rochester • Zoetis Services LLC
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Publication Number
US-12350328-B2
Publication Date
2025-07-08
Expiration Date
Abstract
The present invention provides compositions and methods related to equine live-attenuated influenza vaccines. In one aspect, the invention relates to a composition comprising a multivalent equine live-attenuated influenza vaccine comprising a first live-attenuated influenza virus expressing one or more antigens of a clade 1 H3N8 equine influenza virus; and a second live-attenuated influenza virus expressing one or more antigens of a clade 2 H3N8 equine influenza virus, wherein the second live-attenuated influenza virus expresses HA, NA, or a combination thereof of A/equine/Lancashire/1/2016 H3N8.
Core Innovation
The invention relates to an equine multivalent immunological composition comprising two or more equine live-attenuated influenza viruses (LAIV). The composition comprises a first LAIV expressing one or more antigens of a clade 1 H3N8 equine influenza virus and a second LAIV expressing one or more antigens of a clade 2 H3N8 equine influenza virus, and the second LAIV expresses hemagglutinin (HA), neuraminidase (NA), or a combination thereof of A/equine/Lancashire/1/2016 H3N8.
Each LAIV comprises one or more mutations in one or more of segment 1 and segment 2 of the viral genome. Segment 1 encodes polymerase basic 2 (PB2) protein and segment 2 encodes polymerase basic 1 (PB1) protein, with attenuation engineered by temperature-sensitive/attenuating mutations in these polymerase genes.
The core concept addresses preventing and treating H3N8 equine influenza in horses by using a multivalent LAIV platform that combines clade 1 and clade 2 antigen specificities. The disclosed material includes approaches for constructing bivalent or multivalent compositions by using the ts/att backbone as a master donor virus to swap HA/NA from different Florida clade strains, with rationale and experimental support for immunogenicity, protection, and safety in horses.
Claims Coverage
The provided independent claim defines one multivalent immunological composition with an equine clade 1 LAIV and an equine clade 2 LAIV. The claim includes two main inventive features: antigen/clade assignment between first and second LAIVs, and LAIV genome polymerase mutation requirements across segment 1 (PB2) and segment 2 (PB1).
Multivalent equine LAIV composition of clade 1 and clade 2 antigens
A multivalent immunological composition comprising two or more equine live-attenuated influenza viruses (LAIV), including a first LAIV expressing one or more antigens of a clade 1 H3N8 equine influenza virus, and a second LAIV expressing one or more antigens of a clade 2 H3N8 equine influenza virus, wherein the second LAIV expresses hemagglutinin (HA), neuraminidase (NA), or a combination thereof of A/equine/Lancashire/1/2016 H3N8.
Polymerase gene mutations in segment 1 and segment 2
Each LAIV comprises one or more mutations in one or more of segment 1 and segment 2 of the viral genome, wherein segment 1 encodes a polymerase basic 2 (PB2) protein and segment 2 encodes a polymerase basic 1 (PB1) protein.
Coverage is anchored on a multivalent equine LAIV immunological composition that pairs clade 1 H3N8 antigens with clade 2 H3N8 antigens, including HA and/or NA from A/equine/Lancashire/1/2016 H3N8, while requiring polymerase mutations in PB2 and PB1 segments.
Stated Advantages
Reduced temperatures in horses versus controls in clade 1 and clade 2 LAIV challenge outcomes.
Lower cumulative clinical scores versus controls for both clade 1 and clade 2 challenges.
Markedly reduced live virus shedding (≥53 log reduction) based on nasopharyngeal swab assessment.
Better mucosal delivery.
Stronger innate/adaptive responses.
Possible single-dose protection.
Improved cross-protection.
Safety plus homologous and heterologous challenge protection in horses.
Reduced incidence and severity of clinical disease and fever compared to placebo in a safety/efficacy study of clade 1, clade 2, and bivalent intranasal single-dose vaccines.
Documented Applications
Bivalent EIV LAIV challenge in horses, including clade 1 and clade 2 challenges, with outcomes measured by clinical scoring, temperatures, and live virus shedding assessed from nasopharyngeal swabs.
Safety/efficacy evaluation of clade 1 (TX17), clade 2 (LANC16), and bivalent (TX17+LANC16) intranasal single-dose vaccines in horses challenged with virulent KY/5/12.
Preventing and treating H3N8 equine influenza in horses using a multivalent LAIV platform.
In vivo evaluation and challenge protection in horses using bivalent clade 1/clade 2 LAIVs.
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