Induction of HIV-specific functional immune responses by a multiclade HIV-1 DNA vaccine candidate in healthy Ugandans

Michael A. Eller; Leigh Anne Eller; Marc S. Opollo; Benson J. Ouma; Peter O. Oballah; Lynee Galley; Chitraporn Karnasuta; Silvia Ratto Kim; Merlin L. Robb; Nelson L. Michael; Hannah Kibuuka; Fred Wabwire-Mangen; Barney S. Graham; Deborah L. Birx; Mark S. de Souza; Josephine H. Cox

doi:10.1016/j.vaccine.2007.08.056

Induction of HIV-specific functional immune responses by a multiclade HIV-1 DNA vaccine candidate in healthy Ugandans

Michael A. Eller^*, Leigh Anne Eller, Marc S. Opollo, Benson J. Ouma, Peter O. Oballah, Lynee Galley, Chitraporn Karnasuta, Silvia Ratto Kim, Merlin L. Robb, Nelson L. Michael, Hannah Kibuuka, Fred Wabwire-Mangen, Barney S. Graham, Deborah L. Birx, Mark S. de Souza, Josephine H. Cox

^*Corresponding author for this work

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

22 Scopus citations

Abstract

A phase I randomized, double blind, placebo-controlled trial to assess the immunogenicity of a multiclade HIV-1 DNA plasmid vaccine was conducted in 31 HIV-1-negative Ugandans. Following immunization with DNA at 0, 1, and 2 months, the frequency of HIV-specific immune responses was assessed up to 10 months using a standard chromium release assay (CRA), lymphoproliferative assay (LPA), and antibody dependent cell-mediated cytotoxicity assay (ADCC). Seven of 15 (47%) vaccinees demonstrated CTL activity using the CRA to HIV-1 Env B with responses observed 1 month following the second vaccination and as late as 7 months following complete immunization. Additionally, lymphoproliferative reponses were observed in 14/15 vaccinees against p24. No CTL or LPA responses were observed at baseline or in the placebo group. ADCC activity was minimally induced by DNA vaccination. This study demonstrates that immunization with DNA alone induces CTL and lymphoproliferative responses in a population that will participate in a phase IIb study evaluating HIV-1 DNA priming followed by boosting with a replication-defective recombinant adenovirus vector.

Original language	English
Pages (from-to)	7737-7742
Number of pages	6
Journal	Vaccine
Volume	25
Issue number	45
DOIs	https://doi.org/10.1016/j.vaccine.2007.08.056
State	Published - 7 Nov 2007
Externally published	Yes

Keywords

ADCC
CTL
DNA vaccine
HIV-1
LPA

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10.1016/j.vaccine.2007.08.056

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Eller, M. A., Eller, L. A., Opollo, M. S., Ouma, B. J., Oballah, P. O., Galley, L., Karnasuta, C., Kim, S. R., Robb, M. L., Michael, N. L., Kibuuka, H., Wabwire-Mangen, F., Graham, B. S., Birx, D. L., de Souza, M. S., & Cox, J. H. (2007). Induction of HIV-specific functional immune responses by a multiclade HIV-1 DNA vaccine candidate in healthy Ugandans. Vaccine, 25(45), 7737-7742. https://doi.org/10.1016/j.vaccine.2007.08.056

@article{e2884d971d254367b25e606c3440c5eb,

title = "Induction of HIV-specific functional immune responses by a multiclade HIV-1 DNA vaccine candidate in healthy Ugandans",

abstract = "A phase I randomized, double blind, placebo-controlled trial to assess the immunogenicity of a multiclade HIV-1 DNA plasmid vaccine was conducted in 31 HIV-1-negative Ugandans. Following immunization with DNA at 0, 1, and 2 months, the frequency of HIV-specific immune responses was assessed up to 10 months using a standard chromium release assay (CRA), lymphoproliferative assay (LPA), and antibody dependent cell-mediated cytotoxicity assay (ADCC). Seven of 15 (47%) vaccinees demonstrated CTL activity using the CRA to HIV-1 Env B with responses observed 1 month following the second vaccination and as late as 7 months following complete immunization. Additionally, lymphoproliferative reponses were observed in 14/15 vaccinees against p24. No CTL or LPA responses were observed at baseline or in the placebo group. ADCC activity was minimally induced by DNA vaccination. This study demonstrates that immunization with DNA alone induces CTL and lymphoproliferative responses in a population that will participate in a phase IIb study evaluating HIV-1 DNA priming followed by boosting with a replication-defective recombinant adenovirus vector.",

keywords = "ADCC, CTL, DNA vaccine, HIV-1, LPA",

author = "Eller, {Michael A.} and Eller, {Leigh Anne} and Opollo, {Marc S.} and Ouma, {Benson J.} and Oballah, {Peter O.} and Lynee Galley and Chitraporn Karnasuta and Kim, {Silvia Ratto} and Robb, {Merlin L.} and Michael, {Nelson L.} and Hannah Kibuuka and Fred Wabwire-Mangen and Graham, {Barney S.} and Birx, {Deborah L.} and {de Souza}, {Mark S.} and Cox, {Josephine H.}",

note = "Funding Information: The authors would like to thank the study volunteers for their participation and cooperation in the conduct of this study; Alan Fix and everyone at DAIDS who made this work possible; Tanya Santelli for data analysis; and the Makerere University Walter Reed Project staff for their continued efforts towards HIV vaccine development. This work was supported by the U.S. Army Medical Research and Materiel Command and its Cooperative Agreement (W81XWH-04-02-0005) with the Henry M. Jackson Foundation for the Advancement of Military Medicine and with an Inter Agency Agreement (1Y-A1-26-42-07) with DAIDS. The opinions expressed herein are those of the authors and do not represent the official position of the U.S. Army or Department of Defense.",

year = "2007",

month = nov,

day = "7",

doi = "10.1016/j.vaccine.2007.08.056",

language = "English",

volume = "25",

pages = "7737--7742",

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Eller, MA, Eller, LA, Opollo, MS, Ouma, BJ, Oballah, PO, Galley, L, Karnasuta, C, Kim, SR, Robb, ML, Michael, NL, Kibuuka, H, Wabwire-Mangen, F, Graham, BS, Birx, DL, de Souza, MS & Cox, JH 2007, 'Induction of HIV-specific functional immune responses by a multiclade HIV-1 DNA vaccine candidate in healthy Ugandans', Vaccine, vol. 25, no. 45, pp. 7737-7742. https://doi.org/10.1016/j.vaccine.2007.08.056

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T1 - Induction of HIV-specific functional immune responses by a multiclade HIV-1 DNA vaccine candidate in healthy Ugandans

AU - Eller, Michael A.

AU - Eller, Leigh Anne

AU - Opollo, Marc S.

AU - Ouma, Benson J.

AU - Oballah, Peter O.

AU - Galley, Lynee

AU - Karnasuta, Chitraporn

AU - Kim, Silvia Ratto

AU - Robb, Merlin L.

AU - Michael, Nelson L.

AU - Kibuuka, Hannah

AU - Wabwire-Mangen, Fred

AU - Graham, Barney S.

AU - Birx, Deborah L.

AU - de Souza, Mark S.

AU - Cox, Josephine H.

N1 - Funding Information: The authors would like to thank the study volunteers for their participation and cooperation in the conduct of this study; Alan Fix and everyone at DAIDS who made this work possible; Tanya Santelli for data analysis; and the Makerere University Walter Reed Project staff for their continued efforts towards HIV vaccine development. This work was supported by the U.S. Army Medical Research and Materiel Command and its Cooperative Agreement (W81XWH-04-02-0005) with the Henry M. Jackson Foundation for the Advancement of Military Medicine and with an Inter Agency Agreement (1Y-A1-26-42-07) with DAIDS. The opinions expressed herein are those of the authors and do not represent the official position of the U.S. Army or Department of Defense.

PY - 2007/11/7

Y1 - 2007/11/7

N2 - A phase I randomized, double blind, placebo-controlled trial to assess the immunogenicity of a multiclade HIV-1 DNA plasmid vaccine was conducted in 31 HIV-1-negative Ugandans. Following immunization with DNA at 0, 1, and 2 months, the frequency of HIV-specific immune responses was assessed up to 10 months using a standard chromium release assay (CRA), lymphoproliferative assay (LPA), and antibody dependent cell-mediated cytotoxicity assay (ADCC). Seven of 15 (47%) vaccinees demonstrated CTL activity using the CRA to HIV-1 Env B with responses observed 1 month following the second vaccination and as late as 7 months following complete immunization. Additionally, lymphoproliferative reponses were observed in 14/15 vaccinees against p24. No CTL or LPA responses were observed at baseline or in the placebo group. ADCC activity was minimally induced by DNA vaccination. This study demonstrates that immunization with DNA alone induces CTL and lymphoproliferative responses in a population that will participate in a phase IIb study evaluating HIV-1 DNA priming followed by boosting with a replication-defective recombinant adenovirus vector.

AB - A phase I randomized, double blind, placebo-controlled trial to assess the immunogenicity of a multiclade HIV-1 DNA plasmid vaccine was conducted in 31 HIV-1-negative Ugandans. Following immunization with DNA at 0, 1, and 2 months, the frequency of HIV-specific immune responses was assessed up to 10 months using a standard chromium release assay (CRA), lymphoproliferative assay (LPA), and antibody dependent cell-mediated cytotoxicity assay (ADCC). Seven of 15 (47%) vaccinees demonstrated CTL activity using the CRA to HIV-1 Env B with responses observed 1 month following the second vaccination and as late as 7 months following complete immunization. Additionally, lymphoproliferative reponses were observed in 14/15 vaccinees against p24. No CTL or LPA responses were observed at baseline or in the placebo group. ADCC activity was minimally induced by DNA vaccination. This study demonstrates that immunization with DNA alone induces CTL and lymphoproliferative responses in a population that will participate in a phase IIb study evaluating HIV-1 DNA priming followed by boosting with a replication-defective recombinant adenovirus vector.

KW - ADCC

KW - CTL

KW - DNA vaccine

KW - HIV-1

KW - LPA

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DO - 10.1016/j.vaccine.2007.08.056

M3 - Article

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AN - SCOPUS:35348861788

SN - 0264-410X

VL - 25

SP - 7737

EP - 7742

JO - Vaccine

JF - Vaccine

IS - 45

ER -

Induction of HIV-specific functional immune responses by a multiclade HIV-1 DNA vaccine candidate in healthy Ugandans

Abstract

Keywords

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