Abstract
Methods To improve Gag/Pol specific immunogenicity, some modifications were included comprising (i) re-introduction of the natural gag-pol frameshift allowing budding and release of GPN particles from transduced cells, (ii) inactivation the protease and (iii) separation of Gag (+G) and PolNef (PN) on two plasmids. Following various protocols, different combinations of GPN derivatives, G, PN and Env encoding plasmids were administered i.m. into Balb/c mice to overcome competition for presentation of relevant epitopes.
Highlights
HIV-1 candidate vaccines (DNA-C; NYVAC-C) expressing an artificial polyprotein consisting of Gag, Pol and Nef (GPN) as well as a secreted from of gp120 (E) induced high levels of polyfunctional, HIV-specific CD4+ and CD8+ T-cells in phase I clinical trials (EUROVACC)
The injection of equimolar amounts of G and PN increased Pol specific responses, whereas Gag responses remained on a constant level
Co-administering Env in a mixture with GPN derivatives or G largely abrogated Gag-specific responses and resulted in the induction of almost exclusively Env specific T-cells, whereas injection of Env and GPN in separate muscles as (page number not for citation purposes)
Summary
HIV-1 candidate vaccines (DNA-C; NYVAC-C) expressing an artificial polyprotein consisting of Gag, Pol and Nef (GPN) as well as a secreted from of gp120 (E) induced high levels of polyfunctional, HIV-specific CD4+ and CD8+ T-cells in phase I clinical trials (EUROVACC). Thereby, T cell responses showed some dominance of Env over Gag/Pol reponses
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