 |
Virmugen IntroductionHuman and animal health is threatened by various diseases every day. Acquired as a result of pathogenic microbial agents, infectious diseases are still a major source of mortality throughout the world, contributing to 26% of global mortality in 2001. Of these mortalities, 90% are caused by illnesses such as acute respiratory infections, diarrhoeal diseases, malaria, AIDS, tuberculosis, and measles. Understanding the mechanisms of how pathogens cause disease is critical to finding effective ways to combat infectious disease. One way to combat infectious disease is by vaccines. Vaccines stimulate the immune system and confer protection against pathogenic microorganisms, offering a safe, effective method to prevent disease. Live attenuated vaccines are one type of vaccine which contains a live pathogen that has a mutation in one or more genes. This mutation attenuates the virulence of the live pathogen and makes it relatively safe for the host to be immunized. These vaccines demonstrate two important traits: attenuation in the host and protection against a challenge with the virulent pathogen. Attenuation of a pathogen occurs when the virulence of a pathogen is reduced. However, in order to remain an effective vaccine, the attenuated vaccine is required to be viable. Many attenuated vaccines can therefore still grow inside the host, but growth is greatly limited. Live attenuated vaccines are also able to protect against challenge from the virulent pathogen. The life cycles of these vaccines are similar to the virulent parent pathogens. Therefore, they most likely stimulate the immune system and elicit strong cellular and antibody responses as well as long term or lifelong immunity. The mutations found in live attenuated vaccines are on genes encoding for virulence factors. Virulence factors are the various parts of a pathogen that allow the microbe to cause disease. While all live attenuated vaccines contain mutations in one or more virulence factors, not all virulence factors can be mutated to create a live attenuated vaccine. Some virulence factors can contribute to attenuation, but alone cannot be used to create an attenuated microbe. Other virulence factors can be mutated to induce attenuation of the parent strain, but they do not stimulate the immune system enough to allow for protection. For simplicity, we have used the term virmugens to represent those virulence factors that can be mutated for the development of live attenuated vaccines. For several decades researchers have been developing live attenuated vaccines, but systematic analysis of virmugens has not been performed. To address this, we have developed Virmugen (http://violinet.org/virmugen), a web-based database for virulence factors that can be mutated to create a live attenuated vaccine. Virmugen stores manually curated virmugens and other associated information, such as related vaccines. Analysis of virmugens is important because it may help to develop future vaccines for existing pathogens and emerging pathogens. Currently, Virmugen has included over 200 virmugens as well as over 170 virmugen-related vaccines. These virmugens have been verified to be valuable for vaccine development against over 50 pathogens. Examples of pathogens include Bacillus anthracis (anthrax), Brucella spp. (brucellosis), influenza virus, and Plasmodium spp. (malaria). Virmugen is periodically updated with additional virmugens and their bioinformatics analyses as well as their related vaccines. All updates are posted on the Virmugen website.
|