“Infectious diseases kill more people worldwide than any other single cause. That’s one of the main reasons I focus on vaccines.  They really have the potential for improving lives and saving lives."  – Shane Crotty, Ph.D.

Shane Crotty is an Associate Member with tenure in the Vaccine Discovery Division. Dr. Crotty's research focus is on immune system memory, with particular interest in the roles of these mechanisms in human vaccines and protection from infectious diseases.  By better understanding these processes, Dr. Crotty hopes new and better vaccines can one day be developed, particularly against deadly diseases like malaria, West Nile virus and tuberculosis, where no good vaccines currently exist.

Dr. Crotty received his B.S. in Biology from the Massachusetts Institute of Technology (MIT) in 1996. He also received a B.S. in Writing from MIT the same year. Dr. Crotty undertook graduate work in virology at the University of California, San Francisco in the Program in Biological Sciences. There he discovered the mechanism of action of the antiviral drug ribavirin, widely used to treat chronic hepatitis C infections. This was important for the future development of new drugs that function like ribavirin but much better.  Dr. Crotty earned his Ph.D. in Biochemistry and Molecular Biology in 2001. He then pursued postdoctoral work at the Emory University Vaccine Center with Dr. Rafi Ahmed from 2001 to 2003, studying aspects of the generation and maintenance of immune memory after viral infections. In 2003, he accepted a faculty position at LIAI.

Dr. Crotty was also recently named a Pew Scholar, marking him as one of the most promising young scientists in the country today. This distinction was given to only 14 other researchers in the country in 2005 and is coupled with a grant to aid Dr. Crotty in pursuing his research goals.

Dr. Crotty is also the author of Ahead of the Curve, a biography of Nobel laureate scientist David Baltimore, published in 2001, and reviewed in The Wall Street Journal, Nature, The Washington Post, Journal of the American Medical Association (JAMA), Nature Medicine, Publishers Weekly, and Discover Magazine.

Shane Crotty, Ph.D., and his team study immunity against infectious diseases. They investigate how the immune system remembers infections and vaccines. By remembering infections and vaccines, the body is protected from becoming infected in the future. Vaccines are one of the most cost-effective medical treatments in modern civilization and are responsible for saving millions of lives. Yet, good vaccines are very difficult to design, and a better understanding of immune memory will facilitate the ability to make new vaccines.

Most recently, Dr. Crotty’s immunity studies have led to the identification of an antibody that quickly fights the smallpox virus.  Dr. Crotty made the discovery while studying immunological memory to the smallpox vaccine, which is considered the “gold standard” of vaccines because it led to the eradication of this disease.  Despite this, the smallpox virus has been the subject of intense research interest worldwide in the last several years, prompted by bioterrorism concerns. The National Institutes of Health (NIH) has expressed interest in stockpiling Dr. Crotty’s antibody treatment nationwide alongside existing stockpiles of the smallpox vaccine. The NIH awarded Dr. Crotty a $7.1 million grant in the spring of 2008 to further those studies. Interest in Dr. Crotty’s research has been high because the younger portion of the U.S. population is not vaccinated against smallpox, and the antibody appears to successfully treat the disease.

Another important way in which Dr. Crotty's lab studies immune memory is by understanding the function of a gene called SH2D1A or SAP. This gene is mutated in the human genetic disease XLP (X-linked lymphoproliferative disease). Children affected by this disease are immunodeficient and usually die from infectious diseases before reaching adulthood. Dr. Crotty has discovered that the SAP gene plays a central role in generation of immune memory. Understanding the role of SAP in greater detail may help XLP patients and may, more broadly, allow for the design of better human vaccines that take advantage of SAP's important role in the process of generating immune memory.

Definition of epitopes and antigens recognized by vaccinia specific immune responses: their conservation in variola virus sequences, and use as a model system to study complex pathogens. Vaccine. 2009

The smallpox vaccine induces an early neutralizing IgM response. Vaccine. 2009 

Heavily isotype-dependent protective activities of human antibodies against vaccinia virus extracellular virion antigen B5. J Virol. 2009 

Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 2009

Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum. J Exp Med 2009 

Exploring immune memory. Interview by Kira Heller. J Exp Med. 2009 

Vaccinia virus extracellular enveloped virion neutralization in vitro and protection in vivo depend on complement. J Virol. 2009 

Vaccinia virus extracellular enveloped virion neutralization in vitro and protection in vivo depend on complement. J Virol. 2009

Bcl6 and Blimp-1 Are Reciprocal and Antagonistic Regulators of T Follicular Helper Cell Differentiation. Science. 2009

Quantitative PCR technique for detecting lymphocytic choriomeningitis virus in vivo. J Virol Methods. 2008

OX40 drives protective vaccinia virus-specific CD8 T cells. J Immunol. 2008

Selective CD4+ T cell help for antibody responses to a large viral pathogen: deterministic linkage of specificities. Immunity. 2008

NKT cells prevent chronic joint inflammation after infection with Borrelia burgdorferi. Proc Natl Acad Sci U S A. 2008

Redundancy and plasticity of neutralizing antibody responses are cornerstone attributes of the human immune response to the smallpox vaccine. Journal of Virology. 2008
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SAP Regulation of Follicular Helper CD4 T Cell Development and Humoral Immunity Is Independent of SLAM and Fyn Kinase1.  The Journal of Immunology. 2007
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Vaccinia Virus H3L Envelope Protein Is a Major Target of Neutralizing Antibodies in Humans and Elicits Protection against Lethal Challenge in Mice. Journal of Virology. 2005
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Profiling the humoral immune response to infection by using proteome microarrays: high-throughput vaccine and diagnostic antigen discovery. Proc Natl Acad Sci U S A. 2005

Tracking human antigen-specific memory B cells: a sensitive and generalized ELISPOT system. J Immunol Methods. 2004

Immune responses to Bacillus anthracis protective antigen in patients with bioterrorism-related cutaneous or inhalation anthrax. J Infect Dis. 2004

Immunological memory in humans. Semin Immunol. 2004

Cutting edge: long-term B cell memory in humans after smallpox vaccination. J Immunol. 2003

SAP is required for generating long-term humoral immunity. Nature. 2003

Ribavirin's antiviral mechanism of action: lethal mutagenesis? J Mol Med. 2002

Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors. J Virol. 2001

RNA virus error catastrophe: direct molecular test by using ribavirin. Proc Natl Acad Sci U S A. 2001

The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen. Nat Med. 2000

Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen. Nature. 1999

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