Smallpox was once a terror on the world stage. It was a disease that killed more than half of those it infected and would scar its survivors for life, sometimes striking them blind. It was responsible for hundreds of millions of deaths until concentrated vaccination campaigns led to the virus being battled into extinction. The World Health Organization declared smallpox as eradicated in 1979, the first and only disease to ever be purged from nature.

Vaccinia virus, best known as the viral species used to eradicate smallpox, is generally considered the gold standard of vaccines. Today, vaccinia virus represents an extraordinary model to uncover and understand how the body successfully battles infectious agents. However, identifying and analyzing the immune response to a large and complex pathogen – such as vaccinia virus – is confounded by a number of factors, including the stark magnitude of the potential antigenic targets for the host immune response. As a result of these challenges, very little is known about responses to any large pathogen and this limits understanding how protective immunity is established, and how to rationally design new vaccines against large and complex pathogens.

Alessando Sette’s lab is on the forefront of efforts to identify, in precise molecular terms, the body's reactions to large and complex pathogens by using state-of-the-art research. Sette’s group sets out to bridge the vast data processing capacity of theoretical bioinformatics and the real-world results of laboratory experimentation leading to new insights in the etiology of complex pathogens. This groundbreaking research has not only tremendous implication for antiviral research and current vaccine strategies but also for characterizing and modifying immune responses in the context of diagnostics, cancer and allergy.

Sette’s goal is to quickly identifying regions of disease-causing agents that can be recognized by the human immune system (epitopes). This data is then gathered at the Immune Epitope Database and Analysis Resource (IEDB), a groundbreaking global disease information repository created and maintained by Sette’s lab, and aids the development of new medical tools to detect, prevent and treat infectious diseases, cancer and allergies and assists scientists to better understand immune mechanisms.

Michael Croft, Ph.D., is also working with the vaccinia virus. Developed over millions of years, pathogens and especially viruses have many intricate methods that they employ to divert or disable the body’s immune response. By studying these viral and pathogen evasion strategies, researchers may find new ways to help blunt the effects of many diseases.

In conjunction with the labs of Shane Crotty, Ph.D. and Sette, the Croft lab is using its expertise to assist in work regarding the vaccinia virus. As the vaccinia virus has potentially dangerous results for a percentage of the population, it’s important to understand how the body reacts to the virus.

The Crotty lab is looking to the smallpox vaccine to help illuminate the process for creating successful vaccines. The vaccination discovery process is still one that boils down to trial and error based on educated assumptions about diseases and the human body. Crotty is trying to take the guesswork out of vaccine discovery. By studying the smallpox vaccine, considered the gold standard of vaccines, to discover “milestones” of the body’s response to a vaccination, the lab means to identify just what makes a vaccine effective. By singling out critical reactions in the body and determining how they are elicited, it may be possible to create a definitive methodology for vaccine creation and help to guide researchers worldwide in their efforts.

The Crotty lab has also developed, in conjunction with Kirin Pharmaceuticals, USA, smallpox antibodies that can be used to cure the disease in infected individuals. Along with production of smallpox vaccine, these antibodies would be critical in fighting any potential bioterrorism outbreaks of the smallpox virus.

The Crotty lab has also developed, in conjunction with Kirin Pharmaceuticals, USA, smallpox antibodies that can hopefully be used to cure the disease in infected individuals. Along with production of smallpox vaccine, these antibodies would be critical in fighting any potential bioterrorism outbreaks of the smallpox virus.