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

Division of Infectious Disease, Department of Internal Medicine, University of California at Davis, Sacramento, CA 95618, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 11/2009; 201(1):132-41. DOI: 10.1086/648591
Source: PubMed


We report composite results from the Merck phase I program of near-consensus clade B human immunodeficiency virus (HIV) type 1 gag vaccines.
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 gamma enzyme-linked immunospot (ELISpot) response 4 weeks after the final dose.
Overall, 254 (83%) of 307 subjects randomized to the vaccine groups were evaluable. Adjuvants did not enhance immunogenicity of the DNA vaccine. Postboost ELISpot responder frequencies were higher for Ad5-containing 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.
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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    • "• Lastly, a design without a control group was favoured since HIV-specific immune responses can be considered to be close to zero in healthy volunteers at low risk of HIV infection, as attested by immune response measurements in prophylactic HIV vaccine trials at baseline or in a placebo arm [20,21,38-40]. A vaccine strategy meeting the immunogenicity endpoint can therefore be deemed clearly distinct from a potential control group. "
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