WO1992008983A1 - Marqueur de l'hiv/vaccin contre le sida - Google Patents
Marqueur de l'hiv/vaccin contre le sida Download PDFInfo
- Publication number
- WO1992008983A1 WO1992008983A1 PCT/CA1991/000404 CA9100404W WO9208983A1 WO 1992008983 A1 WO1992008983 A1 WO 1992008983A1 CA 9100404 W CA9100404 W CA 9100404W WO 9208983 A1 WO9208983 A1 WO 9208983A1
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- Prior art keywords
- hiv
- antibody
- idiotype
- gpl20
- hiv gpl20
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1036—Retroviridae, e.g. leukemia viruses
- C07K16/1045—Lentiviridae, e.g. HIV, FIV, SIV
- C07K16/1063—Lentiviridae, e.g. HIV, FIV, SIV env, e.g. gp41, gp110/120, gp160, V3, PND, CD4 binding site
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56983—Viruses
- G01N33/56988—HIV or HTLV
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
- G01N33/686—Anti-idiotype
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
Definitions
- This invention relates to the fields of immunology and virology and pertains to immunochemical identification of HIV-1 infection based upon detection of anti-idiotypic anti ⁇ bodies in the serum of HIV-1 infected individuals, and to vaccines for the treatment of HIV.
- This marker is a novel serum autoantibody (serological marker referred to as anti-idiotypic antibody) which has the unique property of specifically reacting to both special determinants (called idiotypes) on the antigen combining sites of anti-HIV gpl20 antibody and CD4 molecules on T lymphocytes. It is proposed that these antibodies may have a protective role against HIV infectivity and spread during the asymptomatic period of HIV infection.
- anti-HIV anti-idiotypic antibodies might provide protection during the early "latency" period and the immunologic mecha ⁇ nisms leading to the loss of protection and progression of disease is currently being investigated.
- SUBSTITIITF eur C Acquired immune deficiency syndrome is a disor ⁇ der caused by infection with Human Immunodeficiency Virus (HIV) .
- HIV Human Immunodeficiency Virus
- Infection with HIV in some individuals results in a profound immunological defect resulting in opportunistic infections with devastating results and eventual death of the patient.
- HIV infection may produce no pathological complications or may result in mild to moderate abnormalities, collectively termed AIDS Related Complex (ARC) .
- ARC AIDS Related Complex
- the f ctors responsible for the progression from ARC to AIDS are not known.
- HIV infected patients to HIV antigens. It appears that early in the infec ⁇ tion patients make antibodies to both the core proteins (gag gene to make Pr55 and enzymatic cleavage to pl7, p24 and a pl5*) and the envelope proteins (env gene to make gpl60 and enzymatic cleavage to gpl20 and gp41) of the virus. However, with the progression of the disease the antibodies to core proteins are diminished or disappear while the antibodies to envelope proteins remain elevated. It has also been shown that a large percentage of AIDS patients have circulating immune complexes in their sera suggestive of an infectious etiology since isolated immune complex material from such patients has significant quantities of HIV antigen or anti ⁇ body.
- core proteins gag gene to make Pr55 and enzymatic cleavage to pl7, p24 and a pl5*
- envelope proteins env gene to make gpl60 and enzymatic cleavage to gpl20 and gp41
- CD4 molecule is important in HIV attachment, penetration and eventual death of helper T cells and, in fact, is the viral receptor per se.
- HIV-seropositive non-AIDS patients had significant levels of anti-CD4+ anti ⁇ bodies.
- 64% were found to be positive for anti- CD4+ antibodies, and in 59% of these, the disease progressed to AIDS within 30 months.
- the 36% who had no significant levels of antibodies had no reproduc ⁇ sion.
- Recent studies have indicated that 10% of HIV-1 in ⁇ fected individuals produce antibodies that recognize the extracellular portion of the CD4 molecule, a region that is distinct from the virus-binding domain. These studies fail to demonstrate the origin and characteristics of these anti- lymphocyte (CD4 specific) antibodies.
- anti-idiotypic antibodies For a number of years, the role of anti-idiotypic antibodies in their capacity to suppress immune responses has been studied.
- anti-idiotypes One of the remarkable properties of anti-idiotypic antibodies is the molecular mimicry of biological receptors. For example, measles virus anti-idiotype inhibits virus infection of primate cells.
- anti-idiotype against anti-measles virus when pre-incubated with Vero cell monolayers, inhibited infection of these cells by measles virus
- anti-idiotype induced complement-mediated lysis of Vero cells has the potential for binding to and mediating de ⁇ struction of host cells bearing the measles virus receptor.
- anti-idiotypic antibodies have been shown to react against virus receptors for retrovirus and hepatitis B on infected cells.
- Anti- idiotypic antibodies include the presence of glomerular immune deposits in rabbits with serum sickness induced by chronic intravenous administration of bovine serum albumin (BSA) containing auto-antibodies. Similarly, in mice, immune deposits induced by injection of bacterial lipopoly-saccha- ride were found to contain idiotypic as well anti-idiotypic immunoglobulin molecules. In addition, anti-idiotypic anti ⁇ bodies (anti-anti-casein) have been shown to be produced in man following milk ingestion. Others have found anti- idiotypic, insulin-mimicking antibodies in the blood of some people suffering from the autoimmune form of diabetes nelli- tus.
- BSA bovine serum albumin
- Anti-idiotypic antibodies can react to the antigenic determinant (idiotype) of the primary anti-HIV gpl20 antibody and thus, even in the absence of persistent viral replication, may cross-react with receptor-bearing CD4 + T lymphocytes as well as on other cells (eg. monocytes or neuronal cells) . This mechanism of binding can be directed either to a non-viral binding region on the CD4 molecule or to an Fc receptor.
- HIV gpl20 glycoprotein has been shown to share a cross-reacting epitope with a surface protein on activated human monocytes and is involved in antigen presentation.
- anti-idiotypic antibodies could conceivably play a protective role in disease progress ⁇ sion.
- Another object of the present invention is to provide a diagnostic kit for the determination of early HIV infection.
- Yet another object of the present invention is to provide a vaccine for treatment of HIV infection.
- a method for detecting anti-HIV gpl20 anti-idiotypes in a biological fluid comprising: a method of detecting HIV infec ⁇ tion in a biological fluid, comprising: a) contacting an anti HIV gpl20 idiotype with a biological fluid under conditions which allow formation of complexes between anti-HIV gpl20 idiotypes and HIV gp anti-idiotypes in said biological fluid; and b) detecting the formation of complexes as an indication of the presence of HIV gpl20 anti-idiotypes in said biologi ⁇ cal fluid.
- a diagnostic kit for the detection of HIV anti-idiotypic anti ⁇ bodies in patient serum comprising:
- a vaccine comprising a purified anti-HIV gpl20 antibody with a specific configuration of an idiotype which mimics a CD4 molecule.
- Fig. 1 is a sketch illustrating a model for anti-idio ⁇ typic antibodies in AIDS
- Fig. 2 is a graph illustrating anti-idiotypic reactivi ⁇ ty over time
- Fig. 3 is a histogram of OKT4 binding to MOLTL T cells and inhibition of binding by anti-idiotypic antibodies in patient serum; Detailed Description of Preferred Embodiments
- the sheep anti-gpl20 antibody binds to peptide T in an ELISA assay, and it can be inhibited (64%) from binding to peptide T by Mab OKT4 (Ortho) .
- Mab anti-gpl20 from Dupont as well as Mab OKT4 do not bind to peptide T.
- Some of the ARC patients' serum anti ⁇ bodies exhibited binding to peptide T and were inhibited (in the range 21-80%) by Mab OKT4. From this experiment, the data indicate that the polyclonal sheep anti-gpl20 antibody as well as some of the patient's antibodies exhibit an idiotype that behaves as an internal image of CD4 (see Figure 1) .
- anti-idiotypic antibody not only binds to the idiotope of anti-HIV gpl20, but also to CD4, and thus, may block HIV infectivity.
- the antibody was used as a probe to detect anti-idio ⁇ type antibodies in HIV-infected patient's serum after isoelectric focusing across a broad pH gradient on agarose gels and capillary blotted onto nitrocellulose paper. After extensive washing and blocking with Tween-20, alkaline phos- phatase conjugated streptavidin was added and the reaction developed for color using BCIP (5-bromo-4-chloro-3-indolyl phosphate-p-toluidine) and NBT (nitroblue tetrazolium) (Bio- Rad) .
- BCIP 5-bromo-4-chloro-3-indolyl phosphate-p-toluidine
- NBT nitrogen blue tetrazolium
- control subjects including normal, healthy individuals (0/12) , a patient with autoimmune uveitis (0/1) , normal subjects (data not in figure) immunized with influenza vac ⁇ cine (0/4) , individuals infected with measles (1/3) , CMV (0/2), mumps (0/2) or VZ (0/3), have very little or no de ⁇ tectable amounts of serum anti-HIV anti-idiotypic antibodies.
- Seronegative gay males were chosen for their known history of frequent sexual contacts with persons diagnosed as ARC or AIDS. Although the presence of strong anti-idiotypic antibody reactions suggests that they are infected with HIV, all 13 persons remain well to date after up to 5 years of follow-up. In an early study, 20/21 seronegative gay males seroconverted with a positive PCR for HIV, and the one who remained seronegative had a positive PCR test for HIV. In a three month follow-up study, 3 of 3 patients showed marked increases in their anti-idiotypic reactivity (Figure 2) .
- the method and test kit is a qualitative as well as a quantitative, non-instrumental, test strip enzyme immunoassay for anti-HIV gpl20 idiotypic antibody in patient serum, which is based on the activity of a tracer.
- the total HIV anti- idiotypic antibody enzyme immuno-assay kit is a two sites method using two antibodies, monoclonal or polyclonal, di ⁇ rected against two different parts of the protein in ques ⁇ tion.
- the first antibody, or idiotype thereof may be fixed on a supporting matrix, such as a nitrocellulose or nylon disk, preferably mounted for ease of handling at one end of a plastic strip, the second antibody is labelled with an en ⁇ zyme, such as an alkaline phosphatase.
- a supporting matrix such as a dry nitrocellu ⁇ lose or nylon disk, preferably, but not essentially, attached to a plastic strip for ease of handling, to which has been immobilized a specific monoclonal or polyclonal antibody, or idiotype thereof against the antibody of interest, namely an HIV gpl20 idiotypic antibody such as a sheep IgG polyclonal antibody (D7324, International Enzymes, CA) specific for the conserved epitope regions of HIV-l gpl20; (b) an enzyme reagent containing an alkaline phosphatase conjugate of a second monoclonal or polyclonal antibody directed against a different site on the protein of interest, such as alkaline phosphatase conjugated goat anti-IgG and (c) a colour de ⁇ veloper solution containing substrate for the enzyme, such as BCIP (5-bromo-4-chloro-3-ind
- the labelled antibody may equally well be la ⁇ belled with a radioisotope or a fluorescent material.
- the strip was then washed in buffer solution and dipped into a colour developer solution containing 5-bromo-4-chloro-3- indolyl phosphate-p-toluidine and nitroblue tetrazolium.
- the disk showed an insoluble blue product resulting from coupled enzyme reactions involving the enzyme, alkaline phosphatase and its substrate.
- the colour intensity was related quanti- tively to the amount of the anti-HIV gpl20 antibody in the patient serum and it was possible to construct a result table of known amounts of protein as well as negative controls.
- a vaccine comprising a puri ⁇ fied anti-HIV gpl20 antibody with a specific configuration which mimics the CD4 molecule should have therapeutic value in inhibiting progression of the HIV positive patient to full blown AIDS.
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Abstract
Les personnes infectées par le virus de l'immunodéfience humaine (virus HIV) possèdent dans leur sérum des anticorps contre la glycoprotéine gp120 de l'HIV (dite HIV gp120), ces anticorps comportant sur les sites de combinaison antigénique un idiotype qui imite celui des molécules CD4. La réaction anti-HIV initiale s'accompagne d'une réaction anti-idiotypique produisant des anticorps qui se lient à la structure idiotypique et également aux molécules CD4 sur les lymphocytes T et sur d'autres cellules avec ce marqueur membraneux, le récepteur viral de l'HIV. L'HIV est bloqué par les anticorps anti-idiotypiques, qui l'empêchent ainsi de se fixer aux cellules CD4 normales, ce qui prévient toute infection cellulaire. Ainsi, un kit comprenant un idiotype anti-HIV gp120, soit sous une forme liée sur une matrice de support soit en solution, aura la propriété, lorsqu'il est mis en réaction avec du sérum contenant un anti-idiotype de gp120, de détecter cet anticorps grâce à l'utilisation de procédés d'immunoanalyse approrpiés qui peuvent faire usage d'une étiquette enzymatique, à radioisotopes ou fluorescente, offrant ainsi des techniques de test alternatives simples pour détecter les infections précoces à l'HIV. Un vaccin comprenant un anticorps anti-HIV gp120 purifié ayant la configuration spécifique avec idiotype qui imite une molécule CD4 est également proposé.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61505890A | 1990-11-19 | 1990-11-19 | |
| US615,058 | 1990-11-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1992008983A1 true WO1992008983A1 (fr) | 1992-05-29 |
Family
ID=24463821
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CA1991/000404 WO1992008983A1 (fr) | 1990-11-19 | 1991-11-18 | Marqueur de l'hiv/vaccin contre le sida |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU8900691A (fr) |
| WO (1) | WO1992008983A1 (fr) |
Cited By (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2703788A1 (fr) * | 1993-04-09 | 1994-10-14 | Toledano Jacques | Dispositif et procédé anti-idiotype de détection immunologique. |
| US6193982B1 (en) | 1995-04-27 | 2001-02-27 | The United States Of America As Represented By The Department Of Health & Human Services | Anti-cyanovirin antibody with an internal image of gp120, a method of use thereof, and a method of using a cyanovirin to induce an immune response to gp120 |
| US6420336B1 (en) | 1995-04-27 | 2002-07-16 | The United States Of America As Represented By The Department Of Health And Human Services | Methods of using cyanovirins topically to inhibit viral infection |
| US6428790B1 (en) | 1995-04-27 | 2002-08-06 | The United States Of America As Represented By The Secretary Department Of Health And Human Services | Cyanovirin conjugates and matrix-anchored cyanovirin and related compositions and methods of use |
| US6780847B2 (en) | 1995-04-27 | 2004-08-24 | The United States Of America As Represented By The Department Of Health And Human Services | Glycosylation-resistant cyanovirins and related conjugates, compositions, nucleic acids, vectors, host cells, methods of production and methods of using nonglycosylated cyanovirins |
| US7048935B2 (en) | 1995-04-27 | 2006-05-23 | The United States Of America As Represented By The Department Of Health And Human Services | Cyanovirin conjugates and matrix-anchored cyanovirin and related compositions and methods of use |
| WO2007085266A1 (fr) | 2006-01-30 | 2007-08-02 | Dako Denmark A/S | Quantification ultra-rapide de lymphocytes-t spécifiques d'antigènes dans du sang entier par cytométrie de flux |
| US7339037B2 (en) | 2001-03-22 | 2008-03-04 | The United States Of America As Represented By The Department Of Health And Human Services | Glycosylation-resistant cyanovirins and related conjugates, compositions, nucleic acids, vectors, host cells, methods of production and methods of using nonglycosylated cyanovirins |
| US7341728B2 (en) * | 2001-05-24 | 2008-03-11 | Agency For Science, Technology And Research | Internalisation of virus into cells |
| US7754420B2 (en) | 1995-04-27 | 2010-07-13 | The United States Of America As Represented By The Department Of Health And Human Services | Methods of using cyanovirins to inhibit viral infection |
| US9404916B2 (en) | 2008-09-20 | 2016-08-02 | University College Cardiff Consultants Limited | Use of a protein kinase inhibitor to detect immune cells, such as T cells |
| US10030065B2 (en) | 2007-07-03 | 2018-07-24 | Dako Denmark A/S | MHC multimers, methods for their generation, labeling and use |
| US10336808B2 (en) | 2007-03-26 | 2019-07-02 | Dako Denmark A/S | MHC peptide complexes and uses thereof in infectious diseases |
| US10369204B2 (en) | 2008-10-02 | 2019-08-06 | Dako Denmark A/S | Molecular vaccines for infectious disease |
| US10611818B2 (en) | 2007-09-27 | 2020-04-07 | Agilent Technologies, Inc. | MHC multimers in tuberculosis diagnostics, vaccine and therapeutics |
| US10722562B2 (en) | 2008-07-23 | 2020-07-28 | Immudex Aps | Combinatorial analysis and repair |
| US10968269B1 (en) | 2008-02-28 | 2021-04-06 | Agilent Technologies, Inc. | MHC multimers in borrelia diagnostics and disease |
| US11992518B2 (en) | 2008-10-02 | 2024-05-28 | Agilent Technologies, Inc. | Molecular vaccines for infectious disease |
| US12258373B2 (en) | 2018-12-17 | 2025-03-25 | Immudex Aps | Panel comprising Borrelia MHC multimers |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988009181A2 (fr) * | 1987-05-29 | 1988-12-01 | Tanox Biosystems, Inc. | Anticorps monoclonaux neutralisant le hiv-1 |
-
1991
- 1991-11-18 AU AU89006/91A patent/AU8900691A/en not_active Abandoned
- 1991-11-18 WO PCT/CA1991/000404 patent/WO1992008983A1/fr active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988009181A2 (fr) * | 1987-05-29 | 1988-12-01 | Tanox Biosystems, Inc. | Anticorps monoclonaux neutralisant le hiv-1 |
Non-Patent Citations (3)
| Title |
|---|
| R.A. MORISSET. 'V International conference on aids: the scientific and social challenge.' 1989 , INTERNATIONAL DEVELOPMENT RESEARCH CENTRE , OTTAWA ONTARIO CANADA See page 650 abstract nr. c.553 : J.J. Drabick et al : "Naturally occurring auto-antibodies to CD4 and the MHC class II molecule in HIV infected patients". * |
| S.D PUTNEY AND D.P. BOLOGNESI 'Aids vaccine research and clinical trials.' June 1990 , MARCEL DEKKER INC , NEW YORK NY USA See chapter 11 on page 241 : R.C. Kennedy et al. ; " CD4-gp120 interaction. Idiotype mimicry as putative vaccines and therapeutics against hiv infection". * |
| THE JOURNAL OF IMMUNOLOGY vol. 145, no. 7, 1 October 1990, BALTIMORE MD USA pages 2199 - 2206; M.S.C. FUNG ET AL: 'MONOCLONAL ANTI-IDIOTYPIC ANTIBODY MIMICKING THE PRINCIPAL NEUTRALISATION SITE IN HIV - 1 GP 120 INDUCES HIV - 1 NEUTRALIZING ANTIBODIES IN RABBITS.' See whole article. * |
Cited By (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2703788A1 (fr) * | 1993-04-09 | 1994-10-14 | Toledano Jacques | Dispositif et procédé anti-idiotype de détection immunologique. |
| US6193982B1 (en) | 1995-04-27 | 2001-02-27 | The United States Of America As Represented By The Department Of Health & Human Services | Anti-cyanovirin antibody with an internal image of gp120, a method of use thereof, and a method of using a cyanovirin to induce an immune response to gp120 |
| US6420336B1 (en) | 1995-04-27 | 2002-07-16 | The United States Of America As Represented By The Department Of Health And Human Services | Methods of using cyanovirins topically to inhibit viral infection |
| US6428790B1 (en) | 1995-04-27 | 2002-08-06 | The United States Of America As Represented By The Secretary Department Of Health And Human Services | Cyanovirin conjugates and matrix-anchored cyanovirin and related compositions and methods of use |
| US6743577B2 (en) | 1995-04-27 | 2004-06-01 | The United States Of America As Represented By The Department Of Health And Human Services | Methods of using cyanovirins to inhibit viral infection |
| US6780847B2 (en) | 1995-04-27 | 2004-08-24 | The United States Of America As Represented By The Department Of Health And Human Services | Glycosylation-resistant cyanovirins and related conjugates, compositions, nucleic acids, vectors, host cells, methods of production and methods of using nonglycosylated cyanovirins |
| US7048935B2 (en) | 1995-04-27 | 2006-05-23 | The United States Of America As Represented By The Department Of Health And Human Services | Cyanovirin conjugates and matrix-anchored cyanovirin and related compositions and methods of use |
| US7105169B2 (en) | 1995-04-27 | 2006-09-12 | The United States Of America As Represented By The Department Of Health And Human Services | Cyanovirin conjugates and matrix-anchored cyanovirin and related compositions and methods of use |
| US7754420B2 (en) | 1995-04-27 | 2010-07-13 | The United States Of America As Represented By The Department Of Health And Human Services | Methods of using cyanovirins to inhibit viral infection |
| US7339037B2 (en) | 2001-03-22 | 2008-03-04 | The United States Of America As Represented By The Department Of Health And Human Services | Glycosylation-resistant cyanovirins and related conjugates, compositions, nucleic acids, vectors, host cells, methods of production and methods of using nonglycosylated cyanovirins |
| US7341728B2 (en) * | 2001-05-24 | 2008-03-11 | Agency For Science, Technology And Research | Internalisation of virus into cells |
| WO2007085266A1 (fr) | 2006-01-30 | 2007-08-02 | Dako Denmark A/S | Quantification ultra-rapide de lymphocytes-t spécifiques d'antigènes dans du sang entier par cytométrie de flux |
| US10336808B2 (en) | 2007-03-26 | 2019-07-02 | Dako Denmark A/S | MHC peptide complexes and uses thereof in infectious diseases |
| US10030065B2 (en) | 2007-07-03 | 2018-07-24 | Dako Denmark A/S | MHC multimers, methods for their generation, labeling and use |
| US10611818B2 (en) | 2007-09-27 | 2020-04-07 | Agilent Technologies, Inc. | MHC multimers in tuberculosis diagnostics, vaccine and therapeutics |
| US10968269B1 (en) | 2008-02-28 | 2021-04-06 | Agilent Technologies, Inc. | MHC multimers in borrelia diagnostics and disease |
| US10722562B2 (en) | 2008-07-23 | 2020-07-28 | Immudex Aps | Combinatorial analysis and repair |
| US9404916B2 (en) | 2008-09-20 | 2016-08-02 | University College Cardiff Consultants Limited | Use of a protein kinase inhibitor to detect immune cells, such as T cells |
| US10369204B2 (en) | 2008-10-02 | 2019-08-06 | Dako Denmark A/S | Molecular vaccines for infectious disease |
| US11992518B2 (en) | 2008-10-02 | 2024-05-28 | Agilent Technologies, Inc. | Molecular vaccines for infectious disease |
| US12258373B2 (en) | 2018-12-17 | 2025-03-25 | Immudex Aps | Panel comprising Borrelia MHC multimers |
Also Published As
| Publication number | Publication date |
|---|---|
| AU8900691A (en) | 1992-06-11 |
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