Embodiments of the invention disclosed herein relate to methods and compositions for bypassing the involvement of CD4+ cells when generating antibody and MHC class I-restricted immune responses, controlling the nature and magnitude of the response, and promoting effective immunologic intervention in viral pathogenesis. More specifically, embodiments relate to immunogenic compositions for vaccination particularly therapeutic vaccination, against HIV and other microbial pathogens that impact functioning of the immune system, their nature, and the order, timing, and route of administration by which they are effectively used.