Antigenicity and Immunogenicity of RV144 Vaccine AIDSVAX Clade E Envelope Immunogen Is Enhanced by a gp120 N-Terminal Deletion

作者: S. Munir Alam , Hua-Xin Liao , Georgia D. Tomaras , Mattia Bonsignori , Chun-Yen Tsao

DOI: 10.1128/JVI.00718-12

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摘要: An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that antibody responses to gp120 V1/V2 region correlated inversely with infection risk. The protein immunogens (A244-rp120 and MN-rgp120) were modified by an N-terminal 11-amino-acid deletion (Δ11) addition a herpes simplex virus (HSV) gD protein-derived tag (gD). We investigated effects these modifications on expression, antigenicity, immunogenicity comparing unmodified A244 both Δ11 only. Analysis gp120, or without gD, demonstrated deletion, was sufficient for enhanced antigenicity C1 region, conformational V2, epitopes. vaccinee serum IgGs bound more avidly than their binding blocked C1, antibodies. Rhesus macaques immunized three different forms proteins gave similar levels titers, although higher titers developed earlier in gp120-immunized animals. Conformational monoclonal antibodies (MAbs) significantly blocking plasma IgG from animals thus indicating qualitative difference induced gp120. These results demonstrate residues immunogen improves envelope immunogenicity.

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