Why don't we have a schistosomiasis vaccine?

Over the past 30 years there has been a concerted effort to understand host immune responses to schistosomes, with the ultimate aim of producing a vaccine for human use. In this issue, Bergquist and Colley, in summarizing recent meetings in Cairo, provide a detailed appraisal of progress towards that goal. It seems an appropriate time to ask why, with reference to Schistosoma mansoni, the development of a vaccine has proved so difficult. This question is explored here by Alan Wilson and Pat Coulson.     

Nematodirus battus 50 years on--a realistic vaccine candidate?

It has been 50 years since the parasitic nematode of lambs, Nematodirus battus, was first described. This parasite has several interesting features; in particular, it induces a rapid, protective immune response in infected young lambs (< 3 months of age), which is not observed if lambs are infected with other trichostrongyle nematodes. Indeed, protection against most gastrointestinal nematodes only develops once lambs are over five to six months old. In this article I suggest that N. battus offers an opportunity to improve our understanding of protective immune responses in young lambs, and could therefore hold a key to rational anti-nematode vaccine developments, based on natural antigens.     

Genome-wide genetic associations with IFNγ response to smallpox vaccine

Smallpox is a deadly and debilitating disease that killed hundreds of millions of people in the past century alone. The use of Vaccinia virus-based smallpox vaccines led to the eradication of smallpox. These vaccines are remarkably effective, inducing the characteristic pustule or "take" at the vaccine site in >97?% of recipients, and inducing a wide spectrum of long-lasting humoral and cellular immune responses. The mechanisms behind inter-individual vaccine-response variability are likely to involve host genetic variation, but have not been fully characterized. We report here the first smallpox vaccine response genome-wide association study of over 1,000 recent recipients of Dryvax(?). The data presented here focus on cellular immune responses as measured by both production of secreted IFNγ and quantitation of IFNγ secreting cells by ELISPOT assay. We identified multiple significant SNP associations in genes (RASA1, ADRA1D, TCF7L1, FAS) that are critical components of signaling pathways that directly control lymphocyte IFNγ production or cytotoxic T cell function. Similarly, we found many associations with SNPs located in genes integral to nerve cell function; findings that, given the complex interplay between the nervous and immune systems, deserve closer examination in follow-up studies.     

Development of a new hydrogen peroxide–based vaccine platform

Safe and effective vaccines are crucial for maintaining public health and reducing the global burden of infectious disease. Here we introduce a new vaccine platform that uses hydrogen peroxide (H(2)O(2)) to inactivate viruses for vaccine production. H(2)O(2) rapidly inactivates both RNA and DNA viruses with minimal damage to antigenic structure or immunogenicity and is a highly effective method when compared with conventional vaccine inactivation approaches such as formaldehyde or β-propiolactone. Mice immunized with H(2)O(2)-inactivated lymphocytic choriomeningitis virus (LCMV) generated cytolytic, multifunctional virus-specific CD8(+) T cells that conferred protection against chronic LCMV infection. Likewise, mice vaccinated with H(2)O(2)-inactivated vaccinia virus or H(2)O(2)-inactivated West Nile virus showed high virus-specific neutralizing antibody titers and were fully protected against lethal challenge. Together, these studies demonstrate that H(2)O(2)-based vaccines are highly immunogenic, provide protection against a range of viral pathogens in mice and represent a promising new approach to future vaccine development.