Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity

Lymphocytic choriomeningitis virus (LCMV) exhibits natural tropism for dendritic cells and represents the prototypic infection that elicits protective CD8(+) T cell (cytotoxic T lymphocyte (CTL)) immunity. Here we have harnessed the immunobiology of this arenavirus for vaccine delivery. By using producer cells constitutively synthesizing the viral glycoprotein (GP), it was possible to replace the gene encoding LCMV GP with vaccine antigens to create replication-defective vaccine vectors. These rLCMV vaccines elicited CTL responses that were equivalent to or greater than those elicited by recombinant adenovirus 5 or recombinant vaccinia virus in their magnitude and cytokine profiles, and they exhibited more effective protection in several models. In contrast to recombinant adenovirus 5, rLCMV failed to elicit vector-specific antibody immunity, which facilitated re-administration of the same vector for booster vaccination. In addition, rLCMV elicited T helper type 1 CD4+ T cell responses and protective neutralizing antibodies to vaccine antigens. These features, together with low seroprevalence in humans, suggest that rLCMV may show utility as a vaccine platform against infectious diseases and cancer.

Small hive beetles, Aethina tumida, are vectors of Paenibacillus larvae

The transmission of honeybee pathogens by free-flying pests, such as small hive beetles (=SHB), would be independent of bees and beekeepers and thereby constitute a new challenge for pathogen control measures. Here we show that larval and adult SHB become contaminated with Paenibacillus larvae spores when exposed to honeybee brood combs with clinical American foulbrood (=AFB) symptoms in the laboratory. This contamination persists in pupae and newly emerged adults. After exposure to contaminated adult SHB, honeybee field colonies showed higher numbers of P. larvae spores in worker and honey samples after five weeks. Despite these results, the rather low number of P. larvae spores on adult SHB suggests that clinical AFB outbreaks are not likely. However, even small spore numbers can be sufficient to spread P. larvae. Therefore, our data clearly show that SHB are vectors of P. larvae. We suggest considering the role of SHB in AFB control in areas where both pests are established.

Enumerating constrained elementary flux vectors of metabolic networks

The concept of elementary vector is generalised to the case where the steady-state space of the metabolic network is not a flux cone but is a general polyhedron due to further inhomogeneous constraints on the flows through some of the reactions. On one hand, this allows to selectively enumerate elementary modes which satisfy certain optimality criteria and this can yield a large computational gain compared with full enumeration. On the other hand, in contrast to the single optimum found by executing a linear program, this enables a comprehensive description of the set of alternate optima often encountered in flux balance analysis. The concepts are illustrated on a metabolic network model of human cardiac mitochondria.