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Immunogenic influenza composition

An immunogenic epitope and influenza technology, applied in the direction of immunoglobulin, antibody medical components, virus antigen components, etc., can solve the problems of short lifespan, side effects of vaccines, inability to deal with bacterial strains and drifting strains, and save money Effect

Inactive Publication Date: 2013-03-20
BIOLOGICAL MIMETICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0019] (3) Cannot deal with recent strains and drifting strains, such as A / Sydney / 5 / 97 in the late 1990s, or deal with potential pandemic strains, such as the Hong Kong H5N1 virus that appeared in 1997;
[0020] (4) The lifespan of protection with existing whole or split influenza vaccines is short and the effect diminishes as genetic changes occur in circulating strains of influenza due to antigenic variation
Alterations may occur in the hemagglutinin of egg-grown influenza virus when compared with primary isolates from infected individuals (Oxford et al., J. Gen. Virol. 72:185-189, 1989; and Rocha et al. ., J.Gen.Virol.74:2513-2518,1993), weakening the potential effect of this vaccine;
[0021] (5) Those who are allergic to eggs have side effects from using vaccines produced in eggs; and
[0022] (6) The current approved production system produces one vaccine per egg infected with influenza virus, and the production time is about 24 weeks
[0023] Thus, currently approved influenza vaccines: (1) do not induce antibodies that neutralize common antigenic variants (recurring annually during an epidemic), as well as subtypes and reassortants; (2) do not Generates a strong immune response in older populations; and (3) does not find broader applicability due to side effects (eg, some vaccines cannot be given to children)

Method used

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Examples

Experimental program
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example 1

[0158] Eight immune-weakening and refocusing hemagglutinin genes from a Wyoming strain (H3N2) were designed and processed as described above. For example, nucleotide replacement by site-directed mutagenesis, introduction of N-linked sequences, complex glycosyl modifications, and / or at 5 major immunogenic and highly variable sites containing strain-specific epitopes where the amino acid is deleted and / or the charge of the amino acid is changed.

[0159] With each change, the introduction of N-linked sequences serves to maximize the size of the attenuation of immunity, especially at larger antigenic sites, while minimizing the number of wild-type amino acid changes required to attenuate the glycoprotein. and any effect of the conformational complexity of the receptor-binding domain. In some cases, only 3 amino acid changes were required. Antigen site B (187-196) targets both B cells and CD4 helper T cells IDNPEs.

[0160] To expedite research, DNA and protein subunit vaccines...

example 2

[0174] Based on multiple considerations, including analysis of immunodominant epitopes, evolution, sequence diversity, and structural data, an immune-refocusing hemagglutinin antigen for the porcine HINlvA / California / 04 / 2009 strain was designed. The following mutations were designed to refocus the immune response away from highly variable immunodominant sites and toward a larger range of protective epitopes.

[0175]As described herein, immune refocusing mutations can take a variety of forms, including deletion, addition, or reduction of glycosylation sites, as well as replacement of epitopes affecting charge, hydrophobicity, or certain other chemical properties. Added glycosylation has the advantage of shielding a relatively large portion of the epitope, while charge changes can be localized to specific sites of antibody-antigen interaction. Due to the high similarity in the protein structure of multiple influenza strains to serotype HA, 3-D structural analysis of the related...

example 3

[0186] HA mutations can be engineered using known methods such as site-specific mutagenesis (quick-change) or gene synthesis. In general, rapid mutation can be used to induce single or double mutations, while gene synthesis can be used for more complex combinations.

[0187] Single point mutations are most helpful in evaluating immune refocusing techniques directed to specific residues of each epitope. However, as pathogens exploit more than one immunodominant variable epitope (deceptive epitope) to evade prolonged immune pressure, improved immune refocusing antigens can incorporate mutations into multiple antigenic sites. Examples of immune refocusing HA antigens containing mutations in 2 or 3 epitopes are Figure 4 , which are listed in Table 3. Examples of immune refocusing HA antigens containing mutations in all 5 epitopes are Figure 5 , which are listed in Table 4. In Table 3 and Table 4, mutations are given by figure 2 Combinations of single point mutations shown ...

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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.

Description

technical field [0001] The present invention relates to immune influenza components. Background technique [0002] Existing approved vaccines for humans and animals are generally effective against so-called "Class One" pathogens. In general, a class of pathogens (such as measles, mumps, and rubella viruses) refers to a class of pathogens that (1) infect or cause serious illness in infants, toddlers, children, and adolescents; (2) carry A relatively stable microbial genome; (3) has a natural history that leads to spontaneous recovery; and (4) induces long-term memory associated with polyclonal and polyepitopic antigen recognition. [0003] In contrast, secondary pathogens such as influenza virus, HIV-1, malaria parasites, mycoplasma (such as those that cause tuberculosis), trypanosomes, schistosomes, leishmania, anaplasma, enteroviruses, Virus, rhinovirus, Norwalk virus, virulent / pathogenic Escherichia coli, Neisseria (Neisseria), streptomyces, non-typeable Haemophilus infl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/145C07K14/11C12N15/44A61K39/395A61K47/48A61P31/16A61P37/00
CPCC07K16/1018C07K2317/33A61K2039/5258C12N2760/16034A61K39/145C07K2317/76A61K2039/545A61K2039/55566A61K2039/70C12N2760/16134A61K39/12A61P31/16A61P37/00
Inventor G·J·托宾P·L·纳拉G·林
Owner BIOLOGICAL MIMETICS
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