In vitro assessment of biological activity and stability of the ALVAC-HIV vaccine
| Autor: | Daniela Damjanovic, Julie Symes, Luciano Ettorre, Liwei He, Ali Azizi, Sanjay Phogat, Jin Su, Lucy Gisonni-Lex, Beata Gajewska, Lidice Bernardo-Reyes, Danielle Salha |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Canarypox medicine.drug_class HIV Core Protein p24 Canarypox virus HIV Antibodies HIV Envelope Protein gp120 Monoclonal antibody Sensitivity and Specificity 03 medical and health sciences Jurkat Cells 0302 clinical medicine Clinical Trials Phase II as Topic medicine Humans 030212 general & internal medicine Vector (molecular biology) HIV vaccine AIDS Vaccines General Veterinary General Immunology and Microbiology biology Public Health Environmental and Occupational Health Antibodies Monoclonal biology.organism_classification Flow Cytometry Virology Antibodies Neutralizing In vitro High-Throughput Screening Assays Titer 030104 developmental biology Infectious Diseases Clinical Trials Phase III as Topic AIDSVAX Molecular Medicine HeLa Cells |
| Zdroj: | Vaccine. 36(37) |
| ISSN: | 1873-2518 |
| Popis: | The first evidence in humans that a safe and effective preventive vaccine for HIV is possible came from the phase III HIV clinical trial RV144 in Thailand. This trial was based on a prime/boost combination of a recombinant canarypox vaccine and two glycoprotein 120 proteins (ALVAC-HIV and AIDSVAX B/E). A pivotal phase IIb/III trial has recently commenced in the Republic of South Africa, for which the infectious titer assay was applied as the quantitative release test for the ALVAC-HIV vaccine. The infectious titer assay measures the ability of the vaccine vector to infect target permissive cells, but does not indicate if the vaccine transgenes are expressed. We have developed a high-throughput biological activity assay that provides results in agreement with the infectious titer assay. This assay uses flow cytometry to quantify expression of ALVAC-HIV encoded proteins gp120 and p24 in human cells. This transgene expression is detected by two cross-clade-reactive, biologically functional human anti-gp120 monoclonal antibodies isolated from clinical trial participants and a commercial mouse anti-p24 monoclonal antibody. The relative biological activity of the vaccine test sample is calculated by comparison of the test sample dose-response curve against that of a reference standard. We show that the novel biological activity assay is specific, accurate, precise, stability-indicating, and robust. The assay is being used for characterization of ALVAC-HIV (vCP2438) product, the efficacy of which is being evaluated in the pivotal phase IIb/III clinical trial HVTN702. The biological activity assay has the potential to indicate vaccine consistency and quality as a complement to the infectious titer assay. |
| Databáze: | OpenAIRE |
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