The enzyme Sialic acid acetylesterase maintains peripheral B cell tolerance and prevents the activation of B cells that see self antigens weakly. This enzyme is of relevance in both murine and human B cells. Inhibiting this esterase may permit the activation of B cells that see conserved but weak epitopes on HIV gp120. The SIAE gene will be knocked down in humanized mice. Both SIAE knockdown humanized mice and Siae mutant conventional mice will be immunized with gp140 trimers in an attempt to ask if inhibition of SIAE favors the generation of neutralizing antibodies against HIV. A novel strategy for HIV vaccination is proposed, that may permit the induction of protective neutralizing antibodies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI090867-02
Application #
8089346
Study Section
Special Emphasis Panel (ZAI1-BP-A (M2))
Program Officer
Shapiro, Stuart Z
Project Start
2010-06-15
Project End
2014-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
2
Fiscal Year
2011
Total Cost
$671,523
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Pillai, Shiv; Netravali, Ilka Arun; Cariappa, Annaiah et al. (2012) Siglecs and immune regulation. Annu Rev Immunol 30:357-92
Kalay, Ersan; Sezgin, Orhan; Chellappa, Vasant et al. (2012) Mutations in RIPK4 cause the autosomal-recessive form of popliteal pterygium syndrome. Am J Hum Genet 90:76-85
Hirschfield, G M; Xie, G; Lu, E et al. (2012) Association of primary biliary cirrhosis with variants in the CLEC16A, SOCS1, SPIB and SIAE immunomodulatory genes. Genes Immun 13:328-35
Pillai, Shiv; Mattoo, Hamid; Cariappa, Annaiah (2011) B cells and autoimmunity. Curr Opin Immunol 23:721-31