Effects of different promoters on the virulence and immunogenicity of a HIV-1 Env-expressing recombinant vaccinia vaccine

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Previously, we developed a vaccination regimen that involves priming with recombinant vaccinia virus LC16m8 Delta (rm8 Delta) strain followed by boosting with a Sendai virus-containing vector. This protocol induced both humoral and cellular immune responses against the HIV-1 envelope protein. The current study aims to optimize this regimen by comparing the immunogenicity and safety of two rm8 Delta strains that express HIV-1 Env under the control of a moderate promoter, p7.5, or a strong promoter, pSFJ1-10. m8 Delta-p7.5-JRCSFenv synthesized less gp160 but showed significantly higher growth potential than m8 Delta-pSFJ-JRCSFenv. The two different rm8 Delta strains induced antigen-specific immunity; however, m8 Delta-pSFJ-JRCSFenv elicited a stronger anti-Env antibody response whereas m8 Delta-p7.5-JRCSFenv induced a stronger Env-specific cytotoxic T lymphocyte response. Both strains were less virulent than the parental m8 Delta strain, suggesting that they would be safe for use in humans. These findings indicate the vaccine can be optimized to induce favorable immune responses (either cellular or humoral), and forms the basis for the rational design of an AIDS vaccine using recombinant vaccinia as the delivery vector. (C) 2013 Elsevier Ltd. All rights reserved.
Elsevier sci ltdの論文
2014-02-07