Novel HIV-1 clade B candidate vaccines designed for HLA-B*5101+ patients protected mice against chimaeric ecotropic HIV-1 challenge
✍ Scribed by Yaowaluck Roshorm; Jessie P. Hong; Naoki Kobayashi; Andrew J. McMichael; David J. Volsky; Mary Jane Potash; Masafumi Takiguchi; Tomáš Hanke
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 367 KB
- Volume
- 39
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
Novel candidate HIV‐1 vaccines have been constructed, which are tailor‐designed for HLA‐B^*^5101^+^ patients infected with HIV‐1 clade B. These vaccines employ novel immunogen HIVB‐B^*^5101 derived from consensus HIV‐1 clade B Gag p17 and p24 regions coupled to two Pol‐derived B^*^5101‐restricted epitopes, which are together with a third B^*^5101 epitope in Gag dominant in HIV‐1‐infected long‐term non‐progressing patients. Both plasmid DNA and modified vaccinia virus Ankara (MVA) vectors supported high expression levels of the HIVB‐B^*^5101 immunogen in cultured cells. Heterologous DNA prime‐recombinant MVA boost regimen induced efficiently HIV‐1‐specific CD8^+^ T‐cell responses in BALB/c mice. These vaccine‐elicited T cells were multifunctional, killed efficiently target cells in vivo, and protected mice against challenge with ecotropic HIV‐1/NL4‐3 and ecotropic HIV‐1/NDK chimaeric viruses with HIV‐1 clade B or D backbones, respectively, and ecotropic murine leukemia virus gp80 envelope, and therefore did so in the absence of anti‐HIV‐1 gp120 antibodies. These results support further development of HIVB‐B^*^5101 vaccines in combined heterologous‐modality regimens. The use of allele‐specific vaccines in humans is discussed in the context of other developments in the HIV‐1 field.