CSBC Cryptosporidium Research - Vaccine Development

The development of vaccines has traditionally relied on the use of live-attenuated pathogens and/or the biochemical and immunological dissection of microorganisms to define potential vaccine targets. Unfortunately, these traditional approaches only identify antigens that are sufficiently abundant to be obtained for vaccine testing. Thus, few antigens are analyzed simultaneously. Both approaches require that the pathogen can be cultured or maintained in the laboratory. As a result, it takes years to identify a single component, clone the gene and produce protein to generate a potential vaccine. Often, as with many parasitic disease; e.g., malaria, Chagas’ Disease, cryptosporidiosis, scientists have been unable to surmount these challenges, and no vaccines are available.

Reverse Vaccinology
An alternative to traditional approaches for vaccine development is provided by the genomic sequences of the pathogens and advances in bioinformatics that permit the extraction of biological information from these sequences. It is not only possible to identify all the possible proteins from whole-genome analysis, but it is also possible to predict features in the proteins that might lead to a potential “good” immunogen. For example, secreted or extracellular proteins, which are more likely to be accessible to the host immune system and therefore represent vaccine targets, can be identified from genomic data using bioinformatic approaches. These potential antigens can be readily and rapidly amplified by PCR and cloned into expression vectors. Thus, secreted or membrane proteins that represent potential vaccine candidates can be expressed using high throughput automated technologies. This approach has been termed reverse vaccinology (Rappuoli, 2001; Mora, M et al. 2003; Rappuoli R, Covacci A. 2003 ).

In the reverse vaccinology approach, all analyses are performed in silico. This represents a significant advantage in that it does not require the growth of the pathogen in the lab. Thus, vaccines for pathogens for which culture systems are unavailable; e.g., Cryptosporidium, can still be developed. Coupling these in silico approaches with expression profiling and proteomic analysis can provide additional data regarding the temporal and physical localization of putative vaccine candidates. These and other related methodologies can be applied to hone the identification of potential vaccine targets that the initial analyses do not address (Serruto D et al. 2004) .






				Introduction & Background on Vaccine Development The development of vaccines has traditionally relied on the use of live-attenuated pathogens and/or the biochemical and immunological dissection of microorganisms to define potential vaccine targets. Unfortunately, these traditional approaches only identify antigens that are sufficiently abundant to be obtained for vaccine testing. Thus, few antigens are analyzed simultaneously. Both approaches require that the pathogen can be cultured or maintained in the laboratory. As a result, it takes years to identify a single component, clone the gene and produce protein to generate a potential vaccine. Often, as with many parasitic disease; e.g., malaria, Chagas’ Disease, cryptosporidiosis, scientists have been unable to surmount these challenges, and no vaccines are available. Reverse Vaccinology An alternative to traditional approaches for vaccine development is provided by the genomic sequences of the pathogens and advances in bioinformatics that permit the extraction of biological information from these sequences. It is not only possible to identify all the possible proteins from whole-genome analysis, but it is also possible to predict features in the proteins that might lead to a potential “good” immunogen. For example, secreted or extracellular proteins, which are more likely to be accessible to the host immune system and therefore represent vaccine targets, can be identified from genomic data using bioinformatic approaches. These potential antigens can be readily and rapidly amplified by PCR and cloned into expression vectors. Thus, secreted or membrane proteins that represent potential vaccine candidates can be expressed using high throughput automated technologies. This approach has been termed reverse vaccinology (Rappuoli, 2001; Mora, M et al. 2003; Rappuoli R, Covacci A. 2003 ). In the reverse vaccinology approach, all analyses are performed in silico. This represents a significant advantage in that it does not require the growth of the pathogen in the lab. Thus, vaccines for pathogens for which culture systems are unavailable; e.g., Cryptosporidium, can still be developed. Coupling these in silico approaches with expression profiling and proteomic analysis can provide additional data regarding the temporal and physical localization of putative vaccine candidates. These and other related methodologies can be applied to hone the identification of potential vaccine targets that the initial analyses do not address (Serruto D et al. 2004) . <--Welcome Continued-->