Enhancing anti-HIV vaccine development: the immunogenic potential of the Minibody format
Advancements in medical research have not yet yielded an effective vaccine against different pathogens, with HIV prevention remaining one of the most crucial medical needs that the scientific community is striving to address. The identification of epitopes on gp120 recognized by broadly neutralizing antibodies is a key approach to vaccine development. By pinpointing these specific epitopes, scientists can better understand how to stimulate the immune system to produce similar antibodies. Following this approach, we have found a way to identify an immunogen that perfectly replicates the conformational epitope of a neutralizing antibody. In fact, we were able to identify a murine antibody, named P1, capable of binding the idiotype of antibodies of an HIV long-term non-progressor patient. We discovered that P1 could also bind the monoclonal antibody b12, one of the first neutralizing antibodies isolated for HIV.
In our most recent work, we aimed to assess the immunogenicity of the P1 antibody, with the goal of eliciting a response akin to b12. To achieve this, we tested three antibody formats:
- one Fab
- two single chains (ScFv)
- two minibodies (Mb)
both with opposite orientations of the light and heavy chain (the variable region of the light chain at the 5’ of the protein, VLVH orientation, or the variable region of the heavy chain, VHVL orientation). We conducted this study employing both in silico and in vivo approaches. Utilizing immunoinformatic tools, we predicted the antigenicity of various P1 formats. Subsequently, in vivo immunization of rabbits was conducted to identify the most effective antigen. The analysis of the humoral immune response in the rabbits indicated that the Fab and MbVHVL antibody formats elicited the strongest responses against HIV-1. However, we believe that the minibody format is more suitable for vaccine development, particularly for RNA-based vaccine development, given its bivalent and monocistronic nature.
This study is significant as it represents the first preliminary research utilizing the minibody format as an antigen. More importantly, this innovative vaccine approach could lay the foundation for developing an oligo-polyclonal anti-idiotype vaccine against HIV-1.
