Chimeric RSV and HMPV F proteins, immunogenic compositions, and methods of use

Inventors

Moore, Martin L. • Todd, Sean • Stobart, Christopher C.

Assignees

Emory University • Children's Healthcare of Atlanta

Abstract

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.

Core Innovation

The document describes a chimeric respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) F protein that includes an hMPV F protein ectodomain together with an RSV F protein cytoplasmic tail and an RSV F protein transmembrane domain. The chimeric F protein comprises SEQ ID NO: 1 or a variant having greater than 93% sequence identity to SEQ ID NO: 1, and the RSV F cytoplasmic tail comprises SEQ ID NO: 15 or SEQ ID NO: 17.

The document further supports chimeric RSV-hMPV F protein configurations by describing live attenuated chimeric RSV-hMPV genomes or antigenomes that incorporate the chimeric F protein architecture. It identifies additional sequence-based features, including codon deoptimization of RSV NS1 and RSV NS2, with an option that may include RSV L, and it references the use of an RSV SH protein gene deletion.

A construct-level disclosure indicates that a specific construct including an RSV backbone with a chimeric F tail could be rescued and grew, while constructs with full-length hMPV F did not. The described combinations of RSV cytoplasmic tail and optional RSV F transmembrane domain placed on an hMPV F ectodomain are therefore presented as improving chimeric virus recovery and/or production within the disclosed context.

Claims Coverage

The independent claims cover three main inventive categories: a chimeric RSV and hMPV F protein with defined ectodomain and RSV tail/TM elements, an immunogenic composition comprising a live chimeric virus that expresses that F design and is defined by sequence identity constraints, and a nucleic acid encoding that chimeric RSV and hMPV F protein.

Across the independent claims, coverage centers on specifying a chimeric RSV-hMPV F protein architecture defined by an hMPV F ectodomain, an RSV F cytoplasmic tail (SEQ ID NO: 15 or SEQ ID NO: 17), and an RSV F transmembrane domain, together with a sequence-identity constraint requiring SEQ ID NO: 1 or variants greater than 93% identity. The same chimeric F definition is extended to nucleic acid and immunogenic composition embodiments.

Stated Advantages

Documented Applications