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Vaccine. 2011 Jan 17;29(4):839-48. doi: 10.1016/j.vaccine.2010.10.083. Epub 2010 Nov 23.

Increased expression and immunogenicity of HIV-1 protease following inactivation of the enzymatic activity.

Author information

1
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute and Swedish Institute for Infectious Disease Control, Nobels väg 18, 171 82 Solna, Stockholm, Sweden. david.hallengard@smi.se

Abstract

HIV-1 protease is an important target for anti-HIV therapy but has not received much attention as a vaccine antigen. To investigate the immunogenic properties of HIV-1 protease, we designed DNA plasmids encoding variants of the protease gene. Mutations resulting in enzymatic inactivation (D25N) and resistance to standard antiretroviral drugs (V82F/I84V) were introduced in order to examine the impact of the enzymatic activity on immunogenicity and the possibility to induce immune responses against drug resistant protease, respectively. The enzymatic inactivation of protease resulted in significantly increased in vitro expression as well as in vivo immunogenicity. The inactivated protease was highly immunogenic in both BALB/c and HLA-A0201 transgenic C57Bl/6 mice, and the immunogenicity was retained when the gene was delivered as a part of a multigene HIV-1 DNA vaccine. The drug resistance mutations hampered both the cellular and humoral immune responses, as the mutations also affect both CD4 and CD8 T cell epitopes. Taken together, our data demonstrates the possibility to drastically increase the immunogenicity of HIV-1 protease.

PMID:
21109032
DOI:
10.1016/j.vaccine.2010.10.083
[Indexed for MEDLINE]

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