Design and evaluation of multi-gene, multi-clade HIV-1 MVA vaccines

Patricia L. Earl; Catherine Cotter; Bernard Moss; Thomas VanCott; Jeffrey Currier; Leigh Anne Eller; Francine McCutchan; Deborah L. Birx; Nelson L. Michael; Mary A. Marovich; Merlin Robb; Josephine H. Cox

doi:10.1016/j.vaccine.2009.07.039

Design and evaluation of multi-gene, multi-clade HIV-1 MVA vaccines

Patricia L. Earl^*
, Catherine Cotter
, Bernard Moss
, Thomas VanCott
, Jeffrey Currier
, Leigh Anne Eller
, Francine McCutchan
, Deborah L. Birx
, Nelson L. Michael
, Mary A. Marovich
, Merlin Robb
, Josephine H. Cox

^*Corresponding author for this work

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

50 Scopus citations

Abstract

Recombinant modified vaccinia virus Ankara (rMVA) expressing HIV-1 genes are promising vaccine candidates. Toward the goal of conducting clinical trials with one or a cocktail of recombinant viruses, four rMVAs expressing env and gag-pol genes from primary HIV-1 isolates representing predominant subtypes from Kenya, Tanzania, Uganda, and Thailand (A, C, D, and CRF01_AE, respectively) were constructed. Efficient expression, processing, and function of Env and Gag were demonstrated. All inserted genes were shown to be genetically stable after repeated passage in cell culture. Strong HIV-specific cellular and humoral immune responses were elicited in mice immunized with each individual vaccine candidate. The MVA/CMDR vaccine candidate expressing CRF01_AE genes has elicited HIV-specific T-cell responses in two independent Phase I clinical trials. Further testing of the other rMVA is warranted.

Original language	English
Pages (from-to)	5885-5895
Number of pages	11
Journal	Vaccine
Volume	27
Issue number	42
DOIs	https://doi.org/10.1016/j.vaccine.2009.07.039
State	Published - 25 Sep 2009

Keywords

HIV vaccine
Immune response
MVA

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10.1016/j.vaccine.2009.07.039

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@article{4e86713fa5294254ab580570bd45bc03,

title = "Design and evaluation of multi-gene, multi-clade HIV-1 MVA vaccines",

abstract = "Recombinant modified vaccinia virus Ankara (rMVA) expressing HIV-1 genes are promising vaccine candidates. Toward the goal of conducting clinical trials with one or a cocktail of recombinant viruses, four rMVAs expressing env and gag-pol genes from primary HIV-1 isolates representing predominant subtypes from Kenya, Tanzania, Uganda, and Thailand (A, C, D, and CRF01\_AE, respectively) were constructed. Efficient expression, processing, and function of Env and Gag were demonstrated. All inserted genes were shown to be genetically stable after repeated passage in cell culture. Strong HIV-specific cellular and humoral immune responses were elicited in mice immunized with each individual vaccine candidate. The MVA/CMDR vaccine candidate expressing CRF01\_AE genes has elicited HIV-specific T-cell responses in two independent Phase I clinical trials. Further testing of the other rMVA is warranted.",

keywords = "HIV vaccine, Immune response, MVA",

author = "Earl, \{Patricia L.\} and Catherine Cotter and Bernard Moss and Thomas VanCott and Jeffrey Currier and Eller, \{Leigh Anne\} and Francine McCutchan and Birx, \{Deborah L.\} and Michael, \{Nelson L.\} and Marovich, \{Mary A.\} and Merlin Robb and Cox, \{Josephine H.\}",

note = "Funding Information: This work was supported in part by the Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health and by the U.S. Army Medical Research and Materiel Command and its Cooperative Agreement (DAMD17-98-2-7007) with the Henry M. Jackson Foundation for the Advancement of Military Medicine. The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals , NRC Publication, 1996 edition. ",

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doi = "10.1016/j.vaccine.2009.07.039",

language = "English",

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journal = "Vaccine",

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AU - Earl, Patricia L.

AU - Cotter, Catherine

AU - Moss, Bernard

AU - VanCott, Thomas

AU - Currier, Jeffrey

AU - Eller, Leigh Anne

AU - McCutchan, Francine

AU - Birx, Deborah L.

AU - Michael, Nelson L.

AU - Marovich, Mary A.

AU - Robb, Merlin

AU - Cox, Josephine H.

N1 - Funding Information: This work was supported in part by the Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health and by the U.S. Army Medical Research and Materiel Command and its Cooperative Agreement (DAMD17-98-2-7007) with the Henry M. Jackson Foundation for the Advancement of Military Medicine. The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals , NRC Publication, 1996 edition.

PY - 2009/9/25

Y1 - 2009/9/25

N2 - Recombinant modified vaccinia virus Ankara (rMVA) expressing HIV-1 genes are promising vaccine candidates. Toward the goal of conducting clinical trials with one or a cocktail of recombinant viruses, four rMVAs expressing env and gag-pol genes from primary HIV-1 isolates representing predominant subtypes from Kenya, Tanzania, Uganda, and Thailand (A, C, D, and CRF01_AE, respectively) were constructed. Efficient expression, processing, and function of Env and Gag were demonstrated. All inserted genes were shown to be genetically stable after repeated passage in cell culture. Strong HIV-specific cellular and humoral immune responses were elicited in mice immunized with each individual vaccine candidate. The MVA/CMDR vaccine candidate expressing CRF01_AE genes has elicited HIV-specific T-cell responses in two independent Phase I clinical trials. Further testing of the other rMVA is warranted.

AB - Recombinant modified vaccinia virus Ankara (rMVA) expressing HIV-1 genes are promising vaccine candidates. Toward the goal of conducting clinical trials with one or a cocktail of recombinant viruses, four rMVAs expressing env and gag-pol genes from primary HIV-1 isolates representing predominant subtypes from Kenya, Tanzania, Uganda, and Thailand (A, C, D, and CRF01_AE, respectively) were constructed. Efficient expression, processing, and function of Env and Gag were demonstrated. All inserted genes were shown to be genetically stable after repeated passage in cell culture. Strong HIV-specific cellular and humoral immune responses were elicited in mice immunized with each individual vaccine candidate. The MVA/CMDR vaccine candidate expressing CRF01_AE genes has elicited HIV-specific T-cell responses in two independent Phase I clinical trials. Further testing of the other rMVA is warranted.

KW - HIV vaccine

KW - Immune response

KW - MVA

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SP - 5885

EP - 5895

JO - Vaccine

JF - Vaccine

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ER -

Design and evaluation of multi-gene, multi-clade HIV-1 MVA vaccines

Abstract

Keywords

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