Host-Pathogen Interaction Laboratory
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Regulation of immunity to Leishmania by p110d: implications for treatment of leishmaniasis Patent Number: USSN  12/244,905 Investors: Jude E Uzonna and Dong Liu Importance: This   patent   was   the   result   of   our   striking   discovery   that   the   p110   isoform   of   phosophoinositide   3   kinase (PI3K)   regulates   immunity   to   Leishmania   major.   Specifically,   we   found   that   an   inactive   knock-in   mutation   in the   p110   gene   renders   the   highly   susceptible   BALB/c   mice   highly   resistant   to   L.   major   infection.   It   also   made the   resistant   mice   hyper-resistant.   Extensive   studies   revealed   that   the   enhanced   resistance   in   these   mice   is related   to   suppression   in   activation,   expansion   and   effector   activities   of   regulatory   T   cells   (Liu   et   al.,   2009, Journal   of   Immunology183:1921).   These   observations   strongly   suggest   that   blocking   this   pathway   with   highly specific   pharmacologic   inhibitors   may   offer   a   potential   new   therapy   for   cutaneous   leishmaniasis.   Thus,   the patent   protects   the   right   of   targeting   this   pathway   for   treatment   of   leishmaniasis.   There   are   currently   few   new and    effective    drugs    available    for    treatment    of    leishmaniasis.    Most    of    the    drugs    currently    used    in    poor countries   (where   the   disease   is   endemic)   for   treatment   of   leishmaniasis   are   old   and   have   undesirable   side effects   (toxicity).   In   addition,   problems   associated   with   drug   resistance   are   of   major   concerns.   Therefore,   the identification   of   new   therapeutic   targets   is   a   major   area   of   research   and   will   be   very   useful   in   combating   the menace of the disease.
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Identification of Leishmania major antigenic peptides and protein that elicit protective T cell response: Implications for vaccination against Leishmaniais  Patent Number: USSN61/937,795 Inventors: Jude E Uzonna and Zhirong Mou Importance: This   is   the   result   their   striking   discovery   using   reverse   immunology   and   proteomics   approaches   to   identify novel   peptides   and   proteins   that   elicit   strong   protective   T   cell   response   in   mice   and   humans.   This   procedure identified   a   protein   that   is   highly   conversed   in   all   pathogenic   species   of   Leishmania,   suggesting   that   it   could offer   cross-specie   protection   against   various   forms   of   leishmaniasis.   We   showed   that   vaccination   with   the immunodominant    peptide    derived    from    this    protein    or    a    DNA    encoding    the    full-length    protein    or recombinant   protein   induced   very   strong   and   durable   protection   against   challenges   with   different   species   of Leishmania,   including   L.   donovani,   the   causative   agent   of   visceral   leishmaniasis.   Importantly,   the   protection conferred    by    the    vaccine    was    independent    of    mouse    genetic    strain.    This    is    a    critical    proof    of    principle demonstration   of   the   potential   of   this   antigen   as   a   potential   vaccine   candidate   against   leishmaniasis.   The identification   of   the   peptides   and   the   corresponding   T   cells   responding   to   the   peptides   made   it   possible   for his    group    to    develop    functional    MHC    class    II    T    cell    receptor    (TCR)    tetramers    for    the    first    time    against Leishmania   (and   perhaps   any   protozoan   parasite)   capable   of   identifying   Leishmania-specific   T   cells   at   clonal level in infected mice.