The Increase of the Magnitude of Spontaneous Viral Blips in Some Participants of Phase II Clinical Trial of Therapeutic Optimized HIV DNA Vaccine Candidate
We developed a candidate DNA vaccine called “DNA-4”consisting of 4 plasmid DNAs encoding Nef, Gag, Pol(rt), and gp140 HIV-1 proteins. The vaccine was found to be safe and immunogenic in a phase I clinical trial. Here we present the results of a phase II clinical trial of R...
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MDPI AG
2019-08-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/7/3/92 |
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| author | Ekaterina Akulova Boris Murashev Sergey Verevochkin Alexey Masharsky Ruslan Al-Shekhadat Valeriy Poddubnyy Olga Zozulya Natalia Vostokova Andrei P. Kozlov |
| author_facet | Ekaterina Akulova Boris Murashev Sergey Verevochkin Alexey Masharsky Ruslan Al-Shekhadat Valeriy Poddubnyy Olga Zozulya Natalia Vostokova Andrei P. Kozlov |
| author_sort | Ekaterina Akulova |
| collection | DOAJ |
| description | We developed a candidate DNA vaccine called “DNA-4”consisting of 4 plasmid DNAs encoding Nef, Gag, Pol(rt), and gp140 HIV-1 proteins. The vaccine was found to be safe and immunogenic in a phase I clinical trial. Here we present the results of a phase II clinical trial of “DNA-4”. This was a multicenter, double-blind, placebo-controlled clinical trial of safety, and dose selection of “DNA-4” in HIV-1 infected people receiving antiretroviral therapy (ART). Fifty-four patients were randomized into 3 groups (17 patients—group DNA-4 0.25 mg, 17 patients—group DNA-4 0.5 mg, 20 patients—the placebo group). All patients were immunized 4 times on days 0, 7, 11, and 15 followed by a 24-week follow-up period. “DNA-4” was found to be safe and well-tolerated at doses of 0.25 mg and 0.5 mg. We found that the amplitudes of the spontaneous viral load increases in three patients immunized with the candidate DNA vaccine were much higher than that in placebo group—2800, 180,000 and 709 copies/mL, suggesting a possible influence of therapeutic DNA vaccination on viral reservoirs in some patients on ART. We hypothesize that this influence was associated with the reactivation of proviral genomes. |
| first_indexed | 2024-04-13T06:56:51Z |
| format | Article |
| id | doaj.art-4799e6fa02604a4ab93ed3367ddf8ae8 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-13T06:56:51Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-4799e6fa02604a4ab93ed3367ddf8ae82022-12-22T02:57:13ZengMDPI AGVaccines2076-393X2019-08-01739210.3390/vaccines7030092vaccines7030092The Increase of the Magnitude of Spontaneous Viral Blips in Some Participants of Phase II Clinical Trial of Therapeutic Optimized HIV DNA Vaccine CandidateEkaterina Akulova0Boris Murashev1Sergey Verevochkin2Alexey Masharsky3Ruslan Al-Shekhadat4Valeriy Poddubnyy5Olga Zozulya6Natalia Vostokova7Andrei P. Kozlov8Laboratory of Molecular Biology of HIV, Research Institute of Ultra Pure Biologicals, St. Petersburg 197110, RussiaThe Biomedical Center, St. Petersburg 194044, RussiaLaboratory of Molecular Biology of HIV, Research Institute of Ultra Pure Biologicals, St. Petersburg 197110, RussiaLaboratory of Molecular Biology of HIV, Research Institute of Ultra Pure Biologicals, St. Petersburg 197110, RussiaLaboratory of Molecular Biology of HIV, Research Institute of Ultra Pure Biologicals, St. Petersburg 197110, RussiaInnovative Pharma, Mosco 143026, RussiaInnovative Pharma, Mosco 143026, RussiaInnovative Pharma, Mosco 143026, RussiaLaboratory of Molecular Biology of HIV, Research Institute of Ultra Pure Biologicals, St. Petersburg 197110, RussiaWe developed a candidate DNA vaccine called “DNA-4”consisting of 4 plasmid DNAs encoding Nef, Gag, Pol(rt), and gp140 HIV-1 proteins. The vaccine was found to be safe and immunogenic in a phase I clinical trial. Here we present the results of a phase II clinical trial of “DNA-4”. This was a multicenter, double-blind, placebo-controlled clinical trial of safety, and dose selection of “DNA-4” in HIV-1 infected people receiving antiretroviral therapy (ART). Fifty-four patients were randomized into 3 groups (17 patients—group DNA-4 0.25 mg, 17 patients—group DNA-4 0.5 mg, 20 patients—the placebo group). All patients were immunized 4 times on days 0, 7, 11, and 15 followed by a 24-week follow-up period. “DNA-4” was found to be safe and well-tolerated at doses of 0.25 mg and 0.5 mg. We found that the amplitudes of the spontaneous viral load increases in three patients immunized with the candidate DNA vaccine were much higher than that in placebo group—2800, 180,000 and 709 copies/mL, suggesting a possible influence of therapeutic DNA vaccination on viral reservoirs in some patients on ART. We hypothesize that this influence was associated with the reactivation of proviral genomes.https://www.mdpi.com/2076-393X/7/3/92HIVAIDSDNA vaccineclinical trialtherapeutic vaccine |
| spellingShingle | Ekaterina Akulova Boris Murashev Sergey Verevochkin Alexey Masharsky Ruslan Al-Shekhadat Valeriy Poddubnyy Olga Zozulya Natalia Vostokova Andrei P. Kozlov The Increase of the Magnitude of Spontaneous Viral Blips in Some Participants of Phase II Clinical Trial of Therapeutic Optimized HIV DNA Vaccine Candidate Vaccines HIV AIDS DNA vaccine clinical trial therapeutic vaccine |
| title | The Increase of the Magnitude of Spontaneous Viral Blips in Some Participants of Phase II Clinical Trial of Therapeutic Optimized HIV DNA Vaccine Candidate |
| title_full | The Increase of the Magnitude of Spontaneous Viral Blips in Some Participants of Phase II Clinical Trial of Therapeutic Optimized HIV DNA Vaccine Candidate |
| title_fullStr | The Increase of the Magnitude of Spontaneous Viral Blips in Some Participants of Phase II Clinical Trial of Therapeutic Optimized HIV DNA Vaccine Candidate |
| title_full_unstemmed | The Increase of the Magnitude of Spontaneous Viral Blips in Some Participants of Phase II Clinical Trial of Therapeutic Optimized HIV DNA Vaccine Candidate |
| title_short | The Increase of the Magnitude of Spontaneous Viral Blips in Some Participants of Phase II Clinical Trial of Therapeutic Optimized HIV DNA Vaccine Candidate |
| title_sort | increase of the magnitude of spontaneous viral blips in some participants of phase ii clinical trial of therapeutic optimized hiv dna vaccine candidate |
| topic | HIV AIDS DNA vaccine clinical trial therapeutic vaccine |
| url | https://www.mdpi.com/2076-393X/7/3/92 |
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