UMIP-249 – A Unique Form of Herpesvirus Vector

Problem: Human immunodeficiency virus (HIV) is able to replicate continuously without relent despite apparently strong humoral and cellular immune responses to the virus. The HIV envelope glycoprotein is shielded with a large amount of carbohydrate and the trimer spike as it exists of the surface of virions is difficult for antibodies to access and difficult for antibodies to block infectivity. HIV-1 is highly variable from one individual to another and even within a single individual evolves to evade ongoing immune responses. The virus encodes a number of gene products that function at least in part to evade intrinsic, innate and adaptive immune responses. And during the course of an infection, HIV-1 gradually destroys CD4+ T lymphocytes, a key orchestrator of adaptive immune responses. The inability of infection by one HIV-1 strain to routinely provide protection against superinfection by a different HIV-1 strain supports this perception of great difficulty in development of a protective vaccine.Two particular vaccine approaches have shown the greatest protective effects in monkey studies to date using virulent strains of simian immunodeficiency virus (SIV) for challenge of Indian-origin rhesus monkeys. The first one consists of live-attenuated strains of SIV, such as those deleted of the nef gene, which have far and away provided the greatest degree of protection against challenge. However, even live attenuated SIV has not provided very good protection against challenge with SIV strains not closely matched in sequence to that of the vaccine strain. This last point seems consistent with the inability of infection by one HIV-1 strain to routinely provide protection against superinfection as described above. The second approach consists of live recombinant forms of a fibroblast-adapted strain of the beta-herpesvirus rhesus cytomegalovirus (CMV). Approximately 50% of macaques vaccinated with these CMV-based vectors manifested complete control of viral replication shortly after SIVmac239 infection. The remaining monkeys not protected by this CMV-based vaccine exhibited persisting SIV levels in plasma indistinguishable from those in control, unvaccinated monkeys. Independent recombinant CMV vectors expressing Gag, or Pol, or Env, or a Rev-Tat-Nef fusion protein (RTN) were combined, but Env-specific antibodies were not elicited. Therefore, there remains a need for a vaccine, which can target multiple virus strains. Technology: Researchers in Dr. Ronald Desrosiers’ laboratory at the University of Miami have developed a recombinant herpesvirus construct comprising nearly a full-length genome of an immunodeficiency virus, e.g., human immunodeficiency virus or simian immunodeficiency virus (SIV), useful as a vaccine to treat or prevent infection of immunodeficiency viruses, such as human immunodeficiency virus (HIV). Peter Gutenberg pxg372@miami.edu 305-243-4604