2011 News

December 4-8, 2011
IBC Antibody Engineering/ Antibody Therapeutics
Annual Meeting in San Diego, CA

Dr. Marasco attending the meeting.

November 11, 2011
Dr. Marasco to speak at the Vatican, Rome, Italy

Dr. Marasco to speak at the Vatican about Adult Stem Cells: Science and the Future of Man and Culture

November 4, 2011 -New Publication
Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV-1 envelope proteins are largely mediated via human CD5+ B cells.  Biswas S, Chang H, Sarkis PTN, Fikrig E, Zhu Q, Marasco WA.  Immunology 2011 Dec: 134(4): 419-33  PMID: 22044090

The first manuscript on "humanized mice" from the Marasco lab was published today in the journal "Immunology".  This study reports a detailed characterization of vaccine-induced antibody responses in the humanized BLT mice model.  The vaccine was directed against both HIV-1 gp140 glycoprotein and West Nile Virus E-protein.  The results demonstrate that this small animal model system can be used as a platform to investigate B cell development and vaccine induced antibody responses against human pathogens.

October 21, 2011
- New Publication
Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro. Abdel-Motal U, Sarkis PTN, Han T, Pudney J, Anderson DJ, Zhu Q, Marasco WA.PLoS One. 2011, 2011;6(10):e26473. PMCID: PMC3198777 

A manuscript describing in vitro studies on a novel microbicide against HIV-1 was published today in pLosOne.  Enhancing anti-HIV-1 humoral immunity at the mucosal cell surface by local expression of human anti-HIV-1 broadly neutralizing antibody (BnAb) b12 that blocks HIV-1 entry would provide an important new intervention that could slow the spread of HIV/AIDS.  We tested the hypothesis that adeno-associated virus (AAV)-BnAb gene transfer to cervico-vaginal epithelial cells will lead to protection against HIV-1 and importantly, blocking transfer and infectivity of HIV-1 in an organotypic human vaginal epithelial cell model.  Furthermore, cervico-vaginal epithelial stem cells were found to be efficiently transduced by the optimal AAV serotype mediated expression of GFP.  This study provides the foundation for a novel microbicide strategy to protect against sexual transmission of HIV-1 by AAV transfer of broadly neutralizing antibody genes to cervico-vaginal epithelial stem cells that could replenish b12 BnAb secreting cells through multiple menstrual cycles.

April 15, 2011 - New Publication
Wide Prevalence of Heterosubtypic Broadly Neutralizing Human Anti-Influenza A Antibodies.  Sui J, Sheehan J, Hwang WC, Bankston LA, Burchett SK, Huang CY, Liddington R, Beigel JH, and Marasco WA.  Clinical Infectious Diseases. 2011 Apr 15;52(8):1003-9.  PMID:21460314.

The online publication was released today in "Clinical Infectious Diseases".  This study examined serum samples obtained from study subjects in an H5N1 vaccine study that were analyzed for crossreactive antibodies (Abs) agianst both subtype hemagglutinins (HAs) and a highly conserved pocket on the HA stem of Group 1 viruses.  Cross-reactive Abs in commercial intravenous immunoglobulin were also examined.  This data quantitatively shows the presence, albeit at low levels, of two populations of heterosubtypic broadly neutralizing antibodies against influenza A in human serum; one population is directed against the HA stem of group 1 influenza A strains and a second population is broadly reactive against both group 1 and group 2.  These observations warrant further investigation to determine how to boost these antibody responses by vaccination to reach sustainable protective levels.  

May 5, 2011 - New Publication- Fine epitope mapping of neutralizing human anti-influenza antibodies
Fine epitope mapping of monoclonal antibodies against hemagglutinin of a highly pathogenic H5N1 influenza virus using yeast surface display. Han T, Sui J, Bennett AS, Liddington RC, Donis RO, Zhu Q and Marasco WA.  Biochem Biophys Res Commun. 2011; Epub ahead of print. PMCID: PMC3119598.

A pressing need remains to expand strategies for accurately determining the regions of the viral surface hemagglutinin (HA) that are recognized by newly discovered anti-influenza neutralizing antibodies.  In this manuscript, a strategy was implemented toward improving our understanding of the neutralizing antibody responses to influenza vaccines and natural antibody responses to seasonal and pandemic strains.  We sought to achieve these goals without prior knowledge of binding sites or the binding stoichiometry of these antibodies. Here, a robust yeast display system for fine epitope mapping of viral surface hemagglutinin (HA)-specific antibodies is demonstrated. We used two human monoclonal antibodies against H5 as a successful test of this novel experimental approach. Thus, our toolchest for studying HA antigenicity, epitope diversity and accessibility in response to natural and experimental influenza infection and vaccines is improved.  In turn, this approach should aid in better understanding of the mechanisms of antibody-mediated viral inhibition and neutralization escape.

Jan 19, 2011
DFCI Spotlight News - Dana-Farber receives $5.6 million grant to develop rapid countermeasures to infectious agents


 Jan 11, 2011 - New Publication
Structural basis of influenza virus neutralization. Han T and Marasco, WA.  Ann N Y Acad Sci. The Year in Immunology. 2011 Jan;1217(1):178-90. PMID: 21251008; PMCID:PMC3062959.

A comprehensive review of the structural basis of antibody-mediated influenza A neutralization was published online today. We review current knowledge of the structure-based mechanisms contributing to the neutralization and neutralization escape of influenza viruses. We also explore the potential for this structure-based approach to overcome the obstacles in developing the highly desired "universal" influenza vaccine.