Compositions and Methods

Abstract

The invention relates to a composition suitable for inducing a T cell mediated immune response against an influenza virus in a vertebrate, said composition comprising nucleic acid encoding one or more epitopes of one or more internal proteins of influenza virus, wherein said composition comprises nucleic acid encoding at least two said epitopes, at least one epitope being from each of two or more internal proteins of influenza virus. The invention also relates to uses of same and to methods involving same.

Description

FIELD OF THE INVENTION[0001]The invention relates to compositions and methods for inducing an immune response against influenza, in particular a T cell mediated immune response.BACKGROUND TO THE INVENTION[0002]Influenza vaccination strategies have been relatively constant for at least about 20 years. Typically, each vaccine comprises inactivated flu virus particles from approximately three different strains. These vaccines are given in order to induce antibody based responses. Each year, the World Health Organisation (WHO) selects the strains which it considers to pose the greatest threat to human health at that time. Two decisions per year are typically issued, one for Northern hemisphere strains and one for Southern hemisphere strains. Following the announcement, manufacturers then have a short period of time in order to make that year's vaccine formulations. This strategy leads to a number of problems. Firstly, due to the short manufacturing window, complications in production ca...

AI Technical Summary

Benefits of technology

[0036]It is an advantage of the invention that by providing excellent cross reactivity, each variant within a particular strain is embraced by the resulting immune response. This advantage flows from the use of conserved antigens, such as NP and / or M1.

[0037]The immune response induced may be easily characterised according to techniques known in the art. For example, the exact peptide(s) used in the immunisation can be employed in assessing the immune response. Alternatively, other strains such as closely related strains or variants of the strain upon which the antigens were based can be used in order to assess cross reactivity or the breadth of coverage provided by the immunisation.

[0038]In one embodiment, the antigens used comprise (eg. consist of) or are derived from the sequence of those antigens in the H3N2 strain. This embodiment has several advantages, such as the availability of the H3N2 virus as a GMP stock for challenge experiments. Furthermore, this strain is the commonest human influenza strain. This strain was first isolated in 1999, and is therefore an advantageously recent isolate.

[0039]The term ‘derived from’ has its natural meaning in the art. In other words, it means that the epitope or antigen is based on or taken from the source material which it is ‘derived from’. This may be via cloning and direct nucleic acid manipulation from the source material, or is more likely to involve derivation from the nucleotide or amino acid sequence of the source material. In such an embodiment, the epitope or antigen is ‘derived from’ the source material if it shares sufficient sequence identity with the source material eg. if it shares at least 60% sequence identity at the amino acid level over at least 10 contiguous amino acids, suitably at least 70% sequence identity at the amino acid level, suitably at least 80% sequence identity at the amino acid level, suitably at least 90% sequence identity at the amino acid level, suitably at least 95% sequence identity at the amino acid level, suitably at least 98% sequence identity at the amino acid level, suitably at least 99% sequence identity at the amino acid level, suitably at least 100% sequence identity at the amino acid level. Suitably this is judged over at least 10 contiguous amino acids, suitably at least 20 amino acids, suitably at least 40 amino acids, suitably at least 60 amino acids, suitably at least 80 amino acids, suitably at least 100 amino acids, suitably at least 150 amino acids, suitably at least 200 amino acids, suitably at least 300 amino acids, suitably over the full length of the sequence of interest. For nucleic acids, the same criteria apply to nucleotide identity and contiguous nucleotide stretches. Suitably degeneracy of the genetic code may be taken into account accordingly.

[0040]It is an advantage of the invention that the antigens used, such as internal antigens, are much more conserved than external protein antigens. This has the beneficial effect that the year to year effectiveness of such a vaccine is significantly higher than a vaccine based on external antigens.

[0041]The terms ‘internal’ and ‘external’ antigens have their normal meaning in the art. Briefly, these refer to the locations of the antigens in / on the structure of the wild type virus. An internal antigen is typically in the viral core or matrix. An external antigen is one which is at least partially exposed at the surface of the viral particle, such as a surface available or surface accessible antigen. External antigens are typically used to try to generate antibody based responses. Preferably the invention excludes the use of external antigens. Suitably the antigens or epitopes of the invention are internal antigens or epitopes.

Problems solved by technology

Therefore, prior art based approaches typically fail to generate protective cross reactivity from strain to strain.

Furthermore, due to the limited number of strains which can be included in any particular given vaccine, at best the protection conferred omits large numbers of potentially threatening viruses.

In addition, lags between the selection of the potentially most threatening strains in any given year and the manufacture of the corresponding vaccine mean that vaccine designers are constantly struggling to keep up as changes in the viral populations will have taken place even before the chosen vaccines are manufactured and administered.

A priori, such approaches would not be expected to work.

One reason is that by choosing internal antigens, it is more difficult to target the virus since those antigens would often be “buried” or masked by the rest of the virus structure.

More importantly, it is not expected that cell based immunity would effectively address influenza pathogenicity.

Therefore, at best it might be hoped that a cell based approach might lead to a reduction in severity of a particular infection, but would not be expected to prevent or ameliorate the disease or infection itself.

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