Comparative cell-mediated immunogenicity of DNA/DNA, DNA/adenovirus type 5 (Ad5), or Ad5/Ad5 HIV-1 clade B gag vaccine prime-boost regimens

David Asmuth, Elizabeth L. Brown, Mark J. Dinubile, Xiao Sun, Carlos Del Rio, Clayton Harro, Michael C. Keefer, James G. Kublin, Sheri A. Dubey, Lisa S. Kierstead, Danilo R. Casimiro, John W. Shiver, Michael N. Robertson, Erin K. Quirk, Devan V. Mehrotra

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Abstract

Background. We report composite results from the Merck phase I program of near-consensus clade B human immunodeficiency virus (HIV) type 1 gag vaccines. Methods. Healthy HIV-uninfected adults were enrolled in 6 blinded placebo-controlled studies evaluating the immunogenicity of (1) a 4-dose regimen of a DNA vaccine, (2) a 3-dose priming regimen of the DNA vaccine with a booster dose of an adenovirus type 5 (Ad5)-vectored vaccine, or (3) a 3-dose regimen of the Ad5 vaccine. The DNA plasmid was provided with or without an aluminum phosphate or CRL1005 adjuvant. The primary end point was the unfractionated HIV-1 gag-specific interferon y enzyme-linked immunospot (ELISpot) response 4 weeks after the final dose. Results. Overall, 254 (83%) of 307 subjects randomized to the vaccine groups were évaluable. Adjuvants did not enhance immunogenicity of the DNA vaccine. Postboost ELISpot responder frequencies were higher for Ad5containing regimens than for the DNA/DNA regimen (33%) but were similar for DNA/Ad5 (55%) and Ad5/Ad5 (50%). DNA/DNA elicited mainly a CD4 response, whereas Ad5/Ad5 elicited mainly a CD8 response; DNA/Ad5 generated CD4 and CD8 responses comparable to those of DNA/DNA and Ad5/Ad5, respectively. Conclusions. The DNA vaccine alone or as a priming regimen for the Ad5 vaccine did not increase unfractionated ELISpot responses compared with the Ad5 vaccine alone. Qualitative T cell responses to different vaccine regimens deserve further study.

Original languageEnglish (US)
Pages (from-to)132-141
Number of pages10
JournalJournal of Infectious Diseases
Volume201
Issue number1
DOIs
StatePublished - Jan 2010

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Adenoviridae
HIV-1
Vaccines
DNA
DNA Vaccines
Adenovirus Vaccines
Enzymes
Cercopithecine Herpesvirus 1
Interferons
Plasmids
Placebos
HIV
T-Lymphocytes

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

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Comparative cell-mediated immunogenicity of DNA/DNA, DNA/adenovirus type 5 (Ad5), or Ad5/Ad5 HIV-1 clade B gag vaccine prime-boost regimens. / Asmuth, David; Brown, Elizabeth L.; Dinubile, Mark J.; Sun, Xiao; Del Rio, Carlos; Harro, Clayton; Keefer, Michael C.; Kublin, James G.; Dubey, Sheri A.; Kierstead, Lisa S.; Casimiro, Danilo R.; Shiver, John W.; Robertson, Michael N.; Quirk, Erin K.; Mehrotra, Devan V.

In: Journal of Infectious Diseases, Vol. 201, No. 1, 01.2010, p. 132-141.

Research output: Contribution to journalArticle

Asmuth, D, Brown, EL, Dinubile, MJ, Sun, X, Del Rio, C, Harro, C, Keefer, MC, Kublin, JG, Dubey, SA, Kierstead, LS, Casimiro, DR, Shiver, JW, Robertson, MN, Quirk, EK & Mehrotra, DV 2010, 'Comparative cell-mediated immunogenicity of DNA/DNA, DNA/adenovirus type 5 (Ad5), or Ad5/Ad5 HIV-1 clade B gag vaccine prime-boost regimens', Journal of Infectious Diseases, vol. 201, no. 1, pp. 132-141. https://doi.org/10.1086/648591
Asmuth, David ; Brown, Elizabeth L. ; Dinubile, Mark J. ; Sun, Xiao ; Del Rio, Carlos ; Harro, Clayton ; Keefer, Michael C. ; Kublin, James G. ; Dubey, Sheri A. ; Kierstead, Lisa S. ; Casimiro, Danilo R. ; Shiver, John W. ; Robertson, Michael N. ; Quirk, Erin K. ; Mehrotra, Devan V. / Comparative cell-mediated immunogenicity of DNA/DNA, DNA/adenovirus type 5 (Ad5), or Ad5/Ad5 HIV-1 clade B gag vaccine prime-boost regimens. In: Journal of Infectious Diseases. 2010 ; Vol. 201, No. 1. pp. 132-141.
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abstract = "Background. We report composite results from the Merck phase I program of near-consensus clade B human immunodeficiency virus (HIV) type 1 gag vaccines. Methods. Healthy HIV-uninfected adults were enrolled in 6 blinded placebo-controlled studies evaluating the immunogenicity of (1) a 4-dose regimen of a DNA vaccine, (2) a 3-dose priming regimen of the DNA vaccine with a booster dose of an adenovirus type 5 (Ad5)-vectored vaccine, or (3) a 3-dose regimen of the Ad5 vaccine. The DNA plasmid was provided with or without an aluminum phosphate or CRL1005 adjuvant. The primary end point was the unfractionated HIV-1 gag-specific interferon y enzyme-linked immunospot (ELISpot) response 4 weeks after the final dose. Results. Overall, 254 (83{\%}) of 307 subjects randomized to the vaccine groups were {\'e}valuable. Adjuvants did not enhance immunogenicity of the DNA vaccine. Postboost ELISpot responder frequencies were higher for Ad5containing regimens than for the DNA/DNA regimen (33{\%}) but were similar for DNA/Ad5 (55{\%}) and Ad5/Ad5 (50{\%}). DNA/DNA elicited mainly a CD4 response, whereas Ad5/Ad5 elicited mainly a CD8 response; DNA/Ad5 generated CD4 and CD8 responses comparable to those of DNA/DNA and Ad5/Ad5, respectively. Conclusions. The DNA vaccine alone or as a priming regimen for the Ad5 vaccine did not increase unfractionated ELISpot responses compared with the Ad5 vaccine alone. Qualitative T cell responses to different vaccine regimens deserve further study.",
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T1 - Comparative cell-mediated immunogenicity of DNA/DNA, DNA/adenovirus type 5 (Ad5), or Ad5/Ad5 HIV-1 clade B gag vaccine prime-boost regimens

AU - Asmuth, David

AU - Brown, Elizabeth L.

AU - Dinubile, Mark J.

AU - Sun, Xiao

AU - Del Rio, Carlos

AU - Harro, Clayton

AU - Keefer, Michael C.

AU - Kublin, James G.

AU - Dubey, Sheri A.

AU - Kierstead, Lisa S.

AU - Casimiro, Danilo R.

AU - Shiver, John W.

AU - Robertson, Michael N.

AU - Quirk, Erin K.

AU - Mehrotra, Devan V.

PY - 2010/1

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N2 - Background. We report composite results from the Merck phase I program of near-consensus clade B human immunodeficiency virus (HIV) type 1 gag vaccines. Methods. Healthy HIV-uninfected adults were enrolled in 6 blinded placebo-controlled studies evaluating the immunogenicity of (1) a 4-dose regimen of a DNA vaccine, (2) a 3-dose priming regimen of the DNA vaccine with a booster dose of an adenovirus type 5 (Ad5)-vectored vaccine, or (3) a 3-dose regimen of the Ad5 vaccine. The DNA plasmid was provided with or without an aluminum phosphate or CRL1005 adjuvant. The primary end point was the unfractionated HIV-1 gag-specific interferon y enzyme-linked immunospot (ELISpot) response 4 weeks after the final dose. Results. Overall, 254 (83%) of 307 subjects randomized to the vaccine groups were évaluable. Adjuvants did not enhance immunogenicity of the DNA vaccine. Postboost ELISpot responder frequencies were higher for Ad5containing regimens than for the DNA/DNA regimen (33%) but were similar for DNA/Ad5 (55%) and Ad5/Ad5 (50%). DNA/DNA elicited mainly a CD4 response, whereas Ad5/Ad5 elicited mainly a CD8 response; DNA/Ad5 generated CD4 and CD8 responses comparable to those of DNA/DNA and Ad5/Ad5, respectively. Conclusions. The DNA vaccine alone or as a priming regimen for the Ad5 vaccine did not increase unfractionated ELISpot responses compared with the Ad5 vaccine alone. Qualitative T cell responses to different vaccine regimens deserve further study.

AB - Background. We report composite results from the Merck phase I program of near-consensus clade B human immunodeficiency virus (HIV) type 1 gag vaccines. Methods. Healthy HIV-uninfected adults were enrolled in 6 blinded placebo-controlled studies evaluating the immunogenicity of (1) a 4-dose regimen of a DNA vaccine, (2) a 3-dose priming regimen of the DNA vaccine with a booster dose of an adenovirus type 5 (Ad5)-vectored vaccine, or (3) a 3-dose regimen of the Ad5 vaccine. The DNA plasmid was provided with or without an aluminum phosphate or CRL1005 adjuvant. The primary end point was the unfractionated HIV-1 gag-specific interferon y enzyme-linked immunospot (ELISpot) response 4 weeks after the final dose. Results. Overall, 254 (83%) of 307 subjects randomized to the vaccine groups were évaluable. Adjuvants did not enhance immunogenicity of the DNA vaccine. Postboost ELISpot responder frequencies were higher for Ad5containing regimens than for the DNA/DNA regimen (33%) but were similar for DNA/Ad5 (55%) and Ad5/Ad5 (50%). DNA/DNA elicited mainly a CD4 response, whereas Ad5/Ad5 elicited mainly a CD8 response; DNA/Ad5 generated CD4 and CD8 responses comparable to those of DNA/DNA and Ad5/Ad5, respectively. Conclusions. The DNA vaccine alone or as a priming regimen for the Ad5 vaccine did not increase unfractionated ELISpot responses compared with the Ad5 vaccine alone. Qualitative T cell responses to different vaccine regimens deserve further study.

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