The immunogenicity of an HIV-1 Gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy

Jeffrey M. Jacobson; Barbara K. Felber; Huichao Chen; George N. Pavlakis; James I. Mullins; Stephen C. De Rosa; Daniel R. Kuritzkes; Georgia D. Tomaras; Jennifer Kinslow; Yajing Bao; Maxine Olefsky; Margherita Rosati; Jenifer Bear; Jack R. Heptinstall; Lu Zhang; Sheetal Sawant; Drew Hannaman; Gregory M. Laird; Joshua C. Cyktor; Sonya L. Heath; Ann C. Collier; Susan L. Koletar; Babafemi O. Taiwo; Pablo Tebas; David A. Wohl; Pablo F. Belaunzaran-Zamudio; M. Juliana McElrath; Alan L. Landay

doi:10.1097/QAD.0000000000003804

The immunogenicity of an HIV-1 Gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy

Jeffrey M. Jacobson^*, Barbara K. Felber, Huichao Chen, George N. Pavlakis, James I. Mullins, Stephen C. De Rosa, Daniel R. Kuritzkes, Georgia D. Tomaras, Jennifer Kinslow, Yajing Bao, Maxine Olefsky, Margherita Rosati, Jenifer Bear, Jack R. Heptinstall, Lu Zhang, Sheetal Sawant, Drew Hannaman, Gregory M. Laird, Joshua C. Cyktor, Sonya L. HeathAnn C. Collier, Susan L. Koletar, Babafemi O. Taiwo, Pablo Tebas, David A. Wohl, Pablo F. Belaunzaran-Zamudio, M. Juliana McElrath, Alan L. Landay

^*Corresponding author for this work

Medicine, Infectious Diseases Division

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Objective:The primary objective of the study was to assess the immunogenicity of an HIV-1 Gag conserved element DNA vaccine (p24CE DNA) in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART).Design:AIDS Clinical Trials Group A5369 was a phase I/IIa, randomized, double-blind, placebo-controlled study of PWH receiving ART with plasma HIV-1 RNA less than 50 copies/ml, current CD4⁺T-cell counts greater than 500 cells/μl, and nadir CD4⁺T-cell counts greater than 350 cells/μl.Methods:The study enrolled 45 participants randomized 2 : 1 : 1 to receive p24CE DNA vaccine at weeks 0 and 4, followed by p24CE DNA admixed with full-length p55^GagDNA vaccine at weeks 12 and 24 (arm A); full-length p55^GagDNA vaccine at weeks 0, 4, 12, and 24 (arm B); or placebo at weeks 0, 4, 12, and 24 (arm C). The active and placebo vaccines were administered by intramuscular electroporation.Results:There was a modest, but significantly greater increase in the number of conserved elements recognized by CD4⁺and/or CD8⁺T cells in arm A compared with arm C (P = 0.014). The percentage of participants with an increased number of conserved elements recognized by T cells was also highest in arm A (8/18, 44.4%) vs. arm C (0/10, 0.0%) (P = 0.025). There were no significant differences between treatment groups in the change in magnitude of responses to total conserved elements.Conclusion:A DNA-delivered HIV-1 Gag conserved element vaccine boosted by a combination of this vaccine with a full-length p55^GagDNA vaccine induced a new conserved element-directed cellular immune response in approximately half the treated PWH on ART.

Original language	English (US)
Pages (from-to)	963-973
Number of pages	11
Journal	AIDS
Volume	38
Issue number	7
DOIs	https://doi.org/10.1097/QAD.0000000000003804
State	Published - Jun 1 2024

Funding

Sources of funding: Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Numbers UM1 AI068634, UM1 AI068636, and UM1 AI106701, and by funding from the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research to B.K. Felber and G.N. Pavlakis; ACTG Site Grant Numbers: Case Western Reserve University CTU (Site 2501) Grant UM1AI069501, University of Washington Positive Research CRS (Site 1401) Grant UM1AI69481, Ohio State University CRS (Site 2301) Grant UM1AI69494, Northwestern University CRS (Site 2701) Grant UM1AI69471, Alabama CRS (Site 31788) Grant UM1AI69452, Chapel Hill CRS (Site 3201) Grant UL1TR002489, Penn Therapeutics CRS (Site 6201) Grant UM1AI69534, University of Pittsburgh CRS (Site 1001) Grant UM1AI69494, UL1TR001857, Rush University CRS (Site 2702) Grant UM1AI69471, Vanderbilt Therapeutics (VT) CRS (Site 3652) Grant UM1AI69439, UL1 TR002243, Puerto Rico AIDS Clinical Trials Unit CRS (Site 5401) Grant UM1AI69415, University of California, San Francisco HIV/AIDS CRS (Site 801) Grant UM1AI69496, Massachusetts General Hospital CRS (MGH CRS) (Site 101) Grant UM1AI69412, University of Rochester Adult HIV Therapeutic Strategies Network CRS (Site 31787) Grant UM1AI69511, Brigham and Women's Hospital Therapeutics (BWH TCRS) CRS (Site 107) Grant UM1AI69412, University of California Los Angeles CARE Center CRS (Site 601) Grant UM1AI69424; and NIH/NIAID HIV Vaccine Trials Network (HVTN) UM1 AI068618; UM1 AI068614 and Duke Center for AIDS Research (P30 AI064518). Accelevir (G.M.L.) received funding from the National Institutes of Health under award numbers U24AI143503, R44AI124996, NSF1738428. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government Sources of funding: Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Numbers UM1 AI068634, UM1 AI068636, and UM1 AI106701, and by funding from the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research to B.K. Felber and G.N. Pavlakis; ACTG Site Grant Numbers: Case Western Reserve University CTU (Site 2501) Grant UM1AI069501, University of Washington Positive Research CRS (Site 1401) Grant UM1AI69481, Ohio State University CRS (Site 2301) Grant UM1AI69494, Northwestern University CRS (Site 2701) Grant UM1AI69471, Alabama CRS (Site 31788) Grant UM1AI69452, Chapel Hill CRS (Site 3201) Grant UL1TR002489, Penn Therapeutics CRS (Site 6201) Grant UM1AI69534, University of Pittsburgh CRS (Site 1001) Grant UM1AI69494, UL1TR001857, Rush University CRS (Site 2702) Grant UM1AI69471, Vanderbilt Therapeutics (VT) CRS (Site 3652) Grant UM1AI69439, UL1 TR002243, Puerto Rico AIDS Clinical Trials Unit CRS (Site 5401) Grant UM1AI69415, University of California, San Francisco HIV/AIDS CRS (Site 801) Grant UM1AI69496, Massachusetts General Hospital CRS (MGH CRS) (Site 101) Grant UM1AI69412, University of Rochester Adult HIV Therapeutic Strategies Network CRS (Site 31787) Grant UM1AI69511, Brigham and Women's Hospital Therapeutics (BWH TCRS) CRS (Site 107) Grant UM1AI69412, University of California Los Angeles CARE Center CRS (Site 601) Grant UM1AI69424; and NIH/NIAID HIV Vaccine Trials Network (HVTN) UM1 AI068618; UM1 AI068614 and Duke Center for AIDS Research (P30 AI064518). Accelevir (G.M.L.) received funding from the National Institutes of Health under award numbers U24AI143503, R44AI124996, NSF1738428. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Keywords

DNA vaccine
HIV
HIV-1 Gag
clinical trial
conserved epitope
electroporation
therapeutic vaccination

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1097/QAD.0000000000003804

Cite this

Jacobson, J. M., Felber, B. K., Chen, H., Pavlakis, G. N., Mullins, J. I., De Rosa, S. C., Kuritzkes, D. R., Tomaras, G. D., Kinslow, J., Bao, Y., Olefsky, M., Rosati, M., Bear, J., Heptinstall, J. R., Zhang, L., Sawant, S., Hannaman, D., Laird, G. M., Cyktor, J. C., ... Landay, A. L. (2024). The immunogenicity of an HIV-1 Gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy. AIDS, 38(7), 963-973. https://doi.org/10.1097/QAD.0000000000003804

@article{8ade7b04c2fe4031bdb794602756d47e,

title = "The immunogenicity of an HIV-1 Gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy",

abstract = "Objective:The primary objective of the study was to assess the immunogenicity of an HIV-1 Gag conserved element DNA vaccine (p24CE DNA) in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART).Design:AIDS Clinical Trials Group A5369 was a phase I/IIa, randomized, double-blind, placebo-controlled study of PWH receiving ART with plasma HIV-1 RNA less than 50 copies/ml, current CD4+T-cell counts greater than 500 cells/μl, and nadir CD4+T-cell counts greater than 350 cells/μl.Methods:The study enrolled 45 participants randomized 2 : 1 : 1 to receive p24CE DNA vaccine at weeks 0 and 4, followed by p24CE DNA admixed with full-length p55GagDNA vaccine at weeks 12 and 24 (arm A); full-length p55GagDNA vaccine at weeks 0, 4, 12, and 24 (arm B); or placebo at weeks 0, 4, 12, and 24 (arm C). The active and placebo vaccines were administered by intramuscular electroporation.Results:There was a modest, but significantly greater increase in the number of conserved elements recognized by CD4+and/or CD8+T cells in arm A compared with arm C (P = 0.014). The percentage of participants with an increased number of conserved elements recognized by T cells was also highest in arm A (8/18, 44.4\%) vs. arm C (0/10, 0.0\%) (P = 0.025). There were no significant differences between treatment groups in the change in magnitude of responses to total conserved elements.Conclusion:A DNA-delivered HIV-1 Gag conserved element vaccine boosted by a combination of this vaccine with a full-length p55GagDNA vaccine induced a new conserved element-directed cellular immune response in approximately half the treated PWH on ART.",

keywords = "DNA vaccine, HIV, HIV-1 Gag, clinical trial, conserved epitope, electroporation, therapeutic vaccination",

author = "Jacobson, \{Jeffrey M.\} and Felber, \{Barbara K.\} and Huichao Chen and Pavlakis, \{George N.\} and Mullins, \{James I.\} and \{De Rosa\}, \{Stephen C.\} and Kuritzkes, \{Daniel R.\} and Tomaras, \{Georgia D.\} and Jennifer Kinslow and Yajing Bao and Maxine Olefsky and Margherita Rosati and Jenifer Bear and Heptinstall, \{Jack R.\} and Lu Zhang and Sheetal Sawant and Drew Hannaman and Laird, \{Gregory M.\} and Cyktor, \{Joshua C.\} and Heath, \{Sonya L.\} and Collier, \{Ann C.\} and Koletar, \{Susan L.\} and Taiwo, \{Babafemi O.\} and Pablo Tebas and Wohl, \{David A.\} and Belaunzaran-Zamudio, \{Pablo F.\} and McElrath, \{M. Juliana\} and Landay, \{Alan L.\}",

year = "2024",

month = jun,

day = "1",

doi = "10.1097/QAD.0000000000003804",

language = "English (US)",

volume = "38",

pages = "963--973",

journal = "AIDS",

issn = "0269-9370",

publisher = "Lippincott Williams and Wilkins",

number = "7",

}

Jacobson, JM, Felber, BK, Chen, H, Pavlakis, GN, Mullins, JI, De Rosa, SC, Kuritzkes, DR, Tomaras, GD, Kinslow, J, Bao, Y, Olefsky, M, Rosati, M, Bear, J, Heptinstall, JR, Zhang, L, Sawant, S, Hannaman, D, Laird, GM, Cyktor, JC, Heath, SL, Collier, AC, Koletar, SL, Taiwo, BO, Tebas, P, Wohl, DA, Belaunzaran-Zamudio, PF, McElrath, MJ & Landay, AL 2024, 'The immunogenicity of an HIV-1 Gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy', AIDS, vol. 38, no. 7, pp. 963-973. https://doi.org/10.1097/QAD.0000000000003804

TY - JOUR

T1 - The immunogenicity of an HIV-1 Gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy

AU - Jacobson, Jeffrey M.

AU - Felber, Barbara K.

AU - Chen, Huichao

AU - Pavlakis, George N.

AU - Mullins, James I.

AU - De Rosa, Stephen C.

AU - Kuritzkes, Daniel R.

AU - Tomaras, Georgia D.

AU - Kinslow, Jennifer

AU - Bao, Yajing

AU - Olefsky, Maxine

AU - Rosati, Margherita

AU - Bear, Jenifer

AU - Heptinstall, Jack R.

AU - Zhang, Lu

AU - Sawant, Sheetal

AU - Hannaman, Drew

AU - Laird, Gregory M.

AU - Cyktor, Joshua C.

AU - Heath, Sonya L.

AU - Collier, Ann C.

AU - Koletar, Susan L.

AU - Taiwo, Babafemi O.

AU - Tebas, Pablo

AU - Wohl, David A.

AU - Belaunzaran-Zamudio, Pablo F.

AU - McElrath, M. Juliana

AU - Landay, Alan L.

PY - 2024/6/1

Y1 - 2024/6/1

N2 - Objective:The primary objective of the study was to assess the immunogenicity of an HIV-1 Gag conserved element DNA vaccine (p24CE DNA) in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART).Design:AIDS Clinical Trials Group A5369 was a phase I/IIa, randomized, double-blind, placebo-controlled study of PWH receiving ART with plasma HIV-1 RNA less than 50 copies/ml, current CD4+T-cell counts greater than 500 cells/μl, and nadir CD4+T-cell counts greater than 350 cells/μl.Methods:The study enrolled 45 participants randomized 2 : 1 : 1 to receive p24CE DNA vaccine at weeks 0 and 4, followed by p24CE DNA admixed with full-length p55GagDNA vaccine at weeks 12 and 24 (arm A); full-length p55GagDNA vaccine at weeks 0, 4, 12, and 24 (arm B); or placebo at weeks 0, 4, 12, and 24 (arm C). The active and placebo vaccines were administered by intramuscular electroporation.Results:There was a modest, but significantly greater increase in the number of conserved elements recognized by CD4+and/or CD8+T cells in arm A compared with arm C (P = 0.014). The percentage of participants with an increased number of conserved elements recognized by T cells was also highest in arm A (8/18, 44.4%) vs. arm C (0/10, 0.0%) (P = 0.025). There were no significant differences between treatment groups in the change in magnitude of responses to total conserved elements.Conclusion:A DNA-delivered HIV-1 Gag conserved element vaccine boosted by a combination of this vaccine with a full-length p55GagDNA vaccine induced a new conserved element-directed cellular immune response in approximately half the treated PWH on ART.

AB - Objective:The primary objective of the study was to assess the immunogenicity of an HIV-1 Gag conserved element DNA vaccine (p24CE DNA) in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART).Design:AIDS Clinical Trials Group A5369 was a phase I/IIa, randomized, double-blind, placebo-controlled study of PWH receiving ART with plasma HIV-1 RNA less than 50 copies/ml, current CD4+T-cell counts greater than 500 cells/μl, and nadir CD4+T-cell counts greater than 350 cells/μl.Methods:The study enrolled 45 participants randomized 2 : 1 : 1 to receive p24CE DNA vaccine at weeks 0 and 4, followed by p24CE DNA admixed with full-length p55GagDNA vaccine at weeks 12 and 24 (arm A); full-length p55GagDNA vaccine at weeks 0, 4, 12, and 24 (arm B); or placebo at weeks 0, 4, 12, and 24 (arm C). The active and placebo vaccines were administered by intramuscular electroporation.Results:There was a modest, but significantly greater increase in the number of conserved elements recognized by CD4+and/or CD8+T cells in arm A compared with arm C (P = 0.014). The percentage of participants with an increased number of conserved elements recognized by T cells was also highest in arm A (8/18, 44.4%) vs. arm C (0/10, 0.0%) (P = 0.025). There were no significant differences between treatment groups in the change in magnitude of responses to total conserved elements.Conclusion:A DNA-delivered HIV-1 Gag conserved element vaccine boosted by a combination of this vaccine with a full-length p55GagDNA vaccine induced a new conserved element-directed cellular immune response in approximately half the treated PWH on ART.

KW - DNA vaccine

KW - HIV

KW - HIV-1 Gag

KW - clinical trial

KW - conserved epitope

KW - electroporation

KW - therapeutic vaccination

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UR - https://www.scopus.com/inward/citedby.url?scp=85192027993&partnerID=8YFLogxK

U2 - 10.1097/QAD.0000000000003804

DO - 10.1097/QAD.0000000000003804

M3 - Article

C2 - 38051788

AN - SCOPUS:85192027993

SN - 0269-9370

VL - 38

SP - 963

EP - 973

JO - AIDS

JF - AIDS

IS - 7

ER -

The immunogenicity of an HIV-1 Gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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