Can Vaccine Development Be Accelerated by Protein Array Analysis?

IN Discussion Topics, Uncategorized

New Finding for Malaria Vaccine Shows Promise.

Vaccine development has been a key strategy for fighting parasitic and viral diseases such as polio, hepatitis, measles, smallpox, and tuberculosis. Despite the advances in molecular biology, the rate of vaccine development has surprisingly not accelerated over the past century, and many diseases that affect world health remain rampant without an effective vaccine. A number of studies using protein microarrays, with the potential for screening a large number of pathogen protein targets recognized by human antibodies, have recently been used to identify promising targets for elusive vaccines. This approach may lead to an acceleration of effective vaccines and the ability to stay ahead of immune responses to resistant strains of the pathogens.

Malaria (Plasmodium falciparum), for example,  affects millions of people a year, and yet a  vaccine has been particularly elusive. A vaccine for malaria is now a key initiative for the World Health Organization as well as other non-profit organizations addressing the needs of developing countries. Transmitted by mosquitoes mostly in tropical and sub-tropical regions, Malaria results in an estimated half a million deaths per year.  After introduction to the human host, the parasite targets the liver, where it propagates and then releases differentiated forms (merozoites) that infect red blood cells- where the parasite further propagates and releases multiple ‘waves’ of infectious merozoites, further expanding the pathology. Preventative treatment with choloroquine, or other drugs that affect the propagation of the parasite in the liver are not practical for long-term use due to cost and serious side effects and are not completely preventative since drug-resistant strains continue to evolve.

A promising study identifying effective antigen targets for Malaria was recently reported by Felgner et al. As reported by this group,  people living in endemic areas can develop partial immunity to the malaria parasite by developing antibodies to the erythrocyte form. However, complete immunity can be achieved by inoculation of people with chloroquine treatment and injection of sporozoites, the parasitic form involved with the initial infection that targets the liver. In the current report, a protein microarray of over 800 proteins representing about 15% of the entire P. falciparum proteome was probed with serum from naturally exposed subjects and from volunteers treated with chloroquine and sporozoites isolated from mosquitoes. The results demonstrated that the naturally exposed subjects’ immune responses were dominated by the erythrocyte-form of the parasite, while the sporozoite-immunized subjects’ immune responses to both erythrocyte and liver proteins of the parasite.

Previous studies identifying antibody specificity for Malaria have only interrogated less than 1% of the P. falciparum proteome by traditional cloning methods based on genomic sequencing. However, use of protein microarrays has enabled screening a large portion of the parasite’s proteome for antibody recognition from immune or partially-immune subjects. This approach appears to lead to a clearer assessment of vaccine targets as well as the potential to monitor the evolution of immune responses as pathogen strains evolve.