Method for the detection of HIV-1-specific antibodies utilizing a Vpu polypeptide
Inventors
Golding, Hana • Khurana, Surender
Assignees
US Department of Health and Human Services
Publication Number
US-8980546-B2
Publication Date
2015-03-17
Expiration Date
2030-05-21
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Abstract
This invention relates to compositions and methods for the detection of immunodeficiency virus infection, especially immunodeficiency virus-1 (HIV-I) infection. The invention particularly concerns compositions and methods that may be used in HIV vaccine recipients whose sera may contain vaccine-generated anti-HIV-1 antibodies.
Core Innovation
This invention relates to compositions and methods for the detection of immunodeficiency virus infection, especially human immunodeficiency virus-1 (HIV-1) infection. It particularly concerns compositions and methods usable in HIV vaccine recipients whose sera may contain vaccine-generated anti-HIV-1 antibodies, enabling differentiation between vaccine-induced antibodies and those produced after true HIV infection during HIV vaccine trials.
The problem being solved arises because currently, most HIV vaccine candidates are complex products containing multiple viral genes or proteins, leading vaccine recipients' sera to react positively in licensed HIV serodetection assays. This reactivity produces patterns indistinguishable from those of HIV-infected individuals, negatively impacting vaccine trials, early HIV infection detection, blood and plasma donor pools, and causing socio-economic harms such as denied employment and travel. No existing HIV detection assay differentiates between vaccine-generated and infection-generated antibodies, which may deter trial participation and complicate HIV diagnosis.
The invention identifies new HIV-1 (and HIV-2) epitopes characterized by broad reactivity with early serum samples from individuals infected with HIV from all clades, absence of protective antibody or cytotoxic epitopes, and their easy removal from current and future HIV-1 candidates. It employs gene-fragment phage display libraries constructed from the whole HIV-1 genome to identify such epitopes and to construct differential enzyme immunoassays capable of distinguishing infection-induced anti-HIV antibodies from vaccine-induced reactivities. The identified epitopes include novel peptide sequences from HIV-1 GAG-p6, gp41, and Nef genes, as well as HIV-2 GAG-p6 and Env-gp36 peptides, which demonstrate high sensitivity and specificity across diverse HIV clades and subtypes in diagnostic assays.
Claims Coverage
There is one independent claim focused on a method for detecting anti-HIV-1 antibodies in human biological samples by immunoassay using specific peptides.
Method for detecting anti-HIV-1 antibody using immunoassay
A method comprising: (a) contacting a human biological sample with a peptide comprising an epitope recognized by anti-HIV-1 antibody, allowing the antibody to bind and form a peptide-antibody complex; (b) contacting this complex with an anti-HIV-1 antibody binding molecule immobilized on a solid support to allow binding forming an extended complex immobilized on the support; (c) removing unbound antibodies or binding molecules; and (d) determining the presence or concentration of anti-HIV-1 antibody by detecting the extended complex via ELISA or immunochromatographic assay, wherein the epitope is present on a peptide or protein comprising the amino acid sequence of SEQ ID NO:142.
The independent claim recites a sensitive immunoassay method for detection or quantification of anti-HIV-1 antibodies using a peptide epitope from SEQ ID NO:142, employing ELISA or immunochromatographic formats with immobilized binding molecules to form detectable complexes.
Stated Advantages
The assay can distinguish between vaccine-generated antibodies and true HIV infections, enabling early detection of breakthrough infections during vaccine trials.
It prevents false positive serodiagnosis in vaccine recipients, reducing social and economic harms such as denied employment, health insurance, travel, and recruitment to armed forces.
The assay has high sensitivity and specificity across diverse HIV clades and subtypes, detecting anti-HIV antibodies early post-infection.
It is suitable for high throughput, low cost implementation in clinical and blood collection settings worldwide.
Documented Applications
Diagnosis and early detection of HIV-1 and HIV-2 infection, especially distinguishing true HIV infections from vaccine-induced antibody responses during HIV vaccine clinical trials.
Monitoring of intercurrent HIV infections in participants of prophylactic HIV vaccine trials.
Screening of blood and plasma donors to avoid excluding vaccine recipients falsely identified as infected.
Use in immunoassay kits employing ELISA or immunochromatographic lateral flow rapid tests, including point-of-care diagnostics in resource-poor or rural areas.
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