Recommended Readings: Susan Kaech, Ph.D., September 14th

Monday Lecture Series
Monday, September 14th, 2015
4:00 p.m., Carson Family Auditorium (CRC)

Susan Kaech, Ph.D.
Associate Professor of Immunobiology,
Yale School of Medicine
Early Career Scientist,
Howard Hughes Medical Institute

PEPing Up T Cell-mediated Immunity to Viruses and Cancer

Recommended Readings

Empirical Articles

Cui, G., Staron, M. M., Gray, S. M., Ho, P. C., Amezquita, R. A., Wu, J., & Kaech, S. M. (2015). IL-7-induced glycerol transport and TAG synthesis promotes memory CD8+ T cell longevity. Cell, 161(4), 750-761. doi:10.1016/j.cell.2015.03.021.

Laidlaw, B. J., Cui, W., Amezquita, R. A., Gray, S. M., Guan, T., Lu, Y., … & Kaech, S. M. (2015). Production of IL-10 by CD4+ regulatory T cells during the resolution of infection promotes the maturation of memory CD8+ T cells. Nature Immunology, 16(8), 871-879. doi:10.1038/ni.3224

Laidlaw, B. J., Zhang, N., Marshall, H. D., Staron, M. M., Guan, T., Hu, Y., … & Kaech, S. M. (2014). CD4+ T cell help guides formation of CD103+ lung-resident memory CD8+ T cells during influenza viral infection. Immunity, 41(4), 633-645. doi:10.1016/j.immuni.2014.09.007.

Slütter, B., Pewe, L. L., Kaech, S. M., & Harty, J. T. (2013). Lung airway-surveilling CXCR3 hi memory CD8+ T cells are critical for protection against influenza A virus. Immunity, 39(5), 939-948. doi:10.1016/j.immuni.2013.09.013.

Review Paper

Gray, S. M., Kaech, S. M., & Staron, M. M. (2014). The interface between transcriptional and epigenetic control of effector and memory CD8+ T‐cell differentiation. Immunological Reviews, 261(1), 157-168. doi:10.1111/imr.12205.

Kaech, S. M., & Cui, W. (2012). Transcriptional control of effector and memory CD8+ T cell differentiation. Nature Reviews Immunology, 12(11), 749-761. doi:10.1038/nri3307.

The State of Vaccine Development: Toughest Problems Remain Unsolved

Accelerating Next-Generation Vaccine Development for Global Disease Prevention

Koff, W. C. et all    Science  v. 340, 2013

Recent technological advances in molecular genetics, molecular and cellular immunology, structural biology, bioinformatics, computational biology, nanotechnology, formulation methods, and systems biology are ushering in a new era of discovery. However, translation of these advances into vaccines remains impeded by major gaps in our knowledge of human immune responses.

Recommended Readings: Michel C. Nussenzweig, M.D., Ph.D.

Friday Lecture Series

Ph.D. Recruitment Lecture

The HIV Vaccine Problem

Michel C. Nussenzweig, M.D., Ph.D., Sherman Fairchild Professor,

senior physician, The Rockefeller University;

investigator, Howard Hughes Medical Institute

 March 8, 2012

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium

 

Recommended Readings

Mouquet, H., Warncke, M., Scheid, J. F., Seaman, M. S., & Nussenzweig, M. C. (2012). Enhanced HIV-1 neutralization by antibody heteroligation. Proceedings of the National Academy of Sciences of the United States of America, 109(3), 875-880

Nchinda, G., Kuroiwa, J., Oks, M., Trumpfheller, C., Chae, G. P., Huang, Y., . . . Steinman, R. M. (2008). The efficacy of DNA vaccination is enhanced in mice by targeting the encoded protein to dendritic cells. Journal of Clinical Investigation, 118(4), 1427-1436

Scheid, J. F., Mouquet, H., Ueberheide, B., Diskin, R., Klein, F., Oliveira, T. Y. K., . . . Nussenzweig, M. C. (2011). Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science, 333(6049), 1633-1637

Trumpfheller, C., Finke, J. S., López, C. B., Moran, T. M., Moltedo, B., Soares, H., . . . Steinman, R. M. (2006). Intensified and protective CD4 + T cell immunity in mice with anti-dendritic cell HIV gag fusion antibody vaccine. Journal of Experimental Medicine, 203(3), 607-617

Zhou, T., Georgiev, I., Wu, X., Yang, Z. -., Dai, K., Finzi, A., . . . Kwong, P. D. (2010). Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science, 329(5993), 811-817

Recommended Readings: Peter Palese, Ph.D.

Friday Lecture Series

Toward a Universal Influenza Virus Vaccine

Peter Palese, Ph.D., Horace W. Goldsmith Professor and chair,

department of microbiology,

Mount Sinai School of Medicine

 February 1, 2012

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium

Recommended Readings

Bouvier, N. M. and P. Palese. 2008. “The Biology of Influenza Viruses.” Vaccine 26 (SUPPL. 4): D49-D53

Hai, R., A. García-Sastre, D. E. Swayne, and P. Palese. 2011. “A Reassortment-Incompetent Live Attenuated Influenza Virus Vaccine for Protection Against Pandemic Virus Strains.” Journal of Virology 85 (14): 6832-6843

Kashyap, A. K., J. Steel, A. F. Oner, M. A. Dillon, R. E. Swale, K. M. Wall, K. J. Perry, et al. 2008. “Combinatorial Antibody Libraries from Survivors of the Turkish H5N1 Avian Influenza Outbreak Reveal Virus Neutralization Strategies.” Proceedings of the National Academy of Sciences of the United States of America 105 (16): 5986-5991

Medina, R. A., B. Manicassamy, S. Stertz, C. W. Seibert, R. Hai, R. B. Belshe, S. E. Frey, C. F. Basler, P. Palese, and A. Garcí-Sastre. 2010. “Pandemic 2009 H1N1 Vaccine Protects Against 1918 Spanish Influenza Virus.” Nature Communications 1 (3)

Wang, T. T. and P. Palese. 2011. “Catching a Moving Target.” Science 333 (6044): 834-835

Wang, T. T., G. S. Tan, R. Hai, N. Pica, L. Ngai, D. C. Ekiert, I. A. Wilson, A. García-Sastre, T. M. Moran, and P. Palese. 2010. “Vaccination with a Synthetic Peptide from the Influenza Virus Hemagglutinin Provides Protection Against Distinct Viral Subtypes.” Proceedings of the National Academy of Sciences of the United States of America 107 (44): 18979-18984

 

Biologists Produce Malaria Vaccine From Algae

Biologists at the University of California, San Diego have succeeded in engineering algae to produce potential candidates for a vaccine that would prevent transmission of the parasite that causes malaria, an achievement that could pave the way for the development of an inexpensive way to protect billions of people from one of the world’s most prevalent and debilitating diseases. Initial proof-of-principle experiments suggest that such a vaccine could prevent malaria transmission.   Read the report of their research in PLoS ONE. 

Recommended Readings: Bruce Walker, M.D.

Friday Lecture Series

Immune Control and Immune Failure in HIV Infection

Bruce Walker, M.D., Principal Investigator,

Ragon Institute of MGH, MIT and Harvard

April 13, 2012

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium

 

Recommended Readings:

Huang, J., P. S. Burke, T. D. H. Cung, F. Pereyra, I. Toth, B. D. Walker, L. Borges, M. Lichterfeld, and X. G. Yu. 2010. “Leukocyte Immunoglobulin-Like Receptors Maintain Unique Antigen-Presenting Properties of Circulating Myeloid Dendritic Cells in HIV-1-Infected Elite Controllers.” Journal of Virology 84 (18): 9463-9471

Kawashima, Y., K. Pfafferott, J. Frater, P. Matthews, R. Payne, M. Addo, H. Gatanaga, et al. 2009. “Adaptation of HIV-1 to Human Leukocyte Antigen Class I.” Nature 458 (7238): 641-645

Mahalanabis, M., P. Jayaraman, T. Miura, F. Pereyra, E. M. Chester, B. Richardson, B. Walker, and N. L. Haigwood. 2009. “Continuous Viral Escape and Selection by Autologous Neutralizing Antibodies in Drug-Naïve Human Immunodeficiency Virus Controllers.” Journal of Virology 83 (2): 662-672

Matthews, P. C., A. Prendergast, A. Leslie, H. Crawford, R. Payne, C. Rousseau, M. Rolland, et al. 2008. “Central Role of Reverting Mutations in HLA Associations with Human Immunodeficiency Virus Set Point.” Journal of Virology 82 (17): 8548-8559

Pereyra, F., S. Palmer, T. Miura, B. L. Block, A. Wiegand, A. C. Rothchild, B. Baker, et al. 2009. “Persistent Low-Level Viremia in HIV-1 Elite Controllers and Relationship to Immunologic Parameters.” Journal of Infectious Diseases 200 (6): 984-990

Virgin, H. W. and B. D. Walker. 2010. “Immunology and the Elusive AIDS Vaccine.” Nature 464 (7286): 224-231

Nannoparticle Vaccines Providing Boost To Cellular and Humoral Immune Responses

For subunit vaccines, adjuvants play a key role in shaping immunological memory. Nanoparticle (NP) delivery systems for antigens and/or molecular danger signals are promising adjuvants capable of promoting both cellular and humoral immune responses, but in most cases the mechanisms of action of these materials are poorly understood. However, NP vaccines may be a promising strategy to enhance the durability, breadth, and potency of humoral immunity by enhancing key elements of the B-cell response.

Read details in PNAS:  Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tfh cells and promote germinal center induction.

Research Indicates Potential New Class of Vaccines

New research has revealed properties of a potential vaccine adjuvant that suggest it could be useful for enhancing protection against a number of different infections.  These studies  advance the hypothesis that lipid molecules may serve as promising vaccine components. The studies demonstrate that NKT cells can help B cells produce antibodies that recognize lipids, but this does not result in long-lived memory immune responses to the lipid antigens. Second, the studies demonstrate that the lipids, when used as adjuvants to enhance immune responses to more conventional protein antigens, induce memory immune responses against the protein target without inducing a memory response to the lipid itself. Together, these findings suggest a single lipid adjuvant could be used multiple times without losing its effect. The new research also characterizes how NKT cells help B cells produce antibodies when lipids are used as a vaccine adjuvant.

This new data is published in the January 2012 issue of the journal Nature Immunology.

Recommended Readings: Sarah Schlesinger M.D. March 7, 2011

Monday Lecture Series

Vaccines that Target Dendritic Cells

Sarah Schlesinger  M.D.

Senior Attending Physician and Associate Professor of Clinical Investigation

 Cellular Physiology and Immunology

March 7, 2011

4:00 p.m.-5:00 p.m. Caspary Auditorium

Recommended Readings

Dhodapkar MV; Sznol M; Wang D, et al.  2010.  Early development of CDX-1401, a novel vaccine targeting NY-ESO-1 to the dendritic cel receptor DEC-205.  Journal of Immunotherapy.  33(8):895-896   Request Article from Markus Library. 

Wanialla CN; Faul EJ; Gomme EA, et al.  2010.  Dendritic cells infected by recombinant rabies virus vaccine vector expressing HIV-1 Gag are immunogenic even in the presence of vector-specific  immunityVaccine.  29(1):130-140

Fiorentini S; Giagulli C; Caccuri F, et al.  2010.  HIV-1 matrix protein p17: a candidate antigen for therapeutic vaccines against AIDS.   Pharmacology & Therapeutics.  128(3):433-444  Request Article from Markus Library.

De Groot A; Buhlmann J; Weber C, et al.  2010.  De-Tolerization of anti-DEC-205 for HIV vaccine delivery.  (abstract only)  AIDS Research and Human Retroviruses.   26(10):A135-A136

Ahlers, JD; and  IM Belyakov.  2009.  Strategies for optimizing targeting and delivery of mucosal HIV vaccinesEuropean Journal of Immunology.  39(10):2657-2669

Kloverpris HN; Karlsson I; Thorn M, et al.  2009.   Immune hierarchy among HIV-1 CD8+T cell epitopes delivered by dendritic cells depends on MHC-I binding irrespective of mode of loading and immunization of HLA-A*0201 mice.  APMIS  117(11):8489-855

Demberg T; and M. Robert-Guroff.  2009.  Mucosal immunity and protection against HIV-SIV infection: strategies and challenges for vaccine design.  International Reviews of Immunology.  28(1-2):20-28   Please request from Markus Library.

Gruber A; Chalmers AS; Rasmussem RA, et al.  2007.  Dendritic cell-based vaccine strategy against human immunodeficiency virus clade C: skewing the immune response toward a helper T cell type 2 profile.   Viral Immunology.  20(1):160-169.