The O-Ag Antibody Response to Francisella Is Distinct in Rodents and Higher Animals and Can Serve as a Correlate of Protection.

Identifying correlates of protection (COPs) for vaccines against lethal human (Hu) pathogens, such as Francisella tularensis (Ft), is problematic, as clinical trials are currently untenable and the relevance of various animal models can be controversial. Previously, Hu trials with the live vaccine strain (LVS) demonstrated ~80% vaccine efficacy against low dose (~50 CFU) challenge; however, protection deteriorated with higher challenge doses (~2000 CFU of SchuS4) and no COPs were established. Here, we describe our efforts to develop clinically relevant, humoral COPs applicable to high-dose, aerosol challenge with S4. First, our serosurvey of LVS-vaccinated Hu and animals revealed that rabbits (Rbs), but not rodents, recapitulate the Hu O-Ag dependent Ab response to Ft. Next, we assayed Rbs immunized with distinct S4-based vaccine candidates (S4ΔclpB, S4ΔguaBA, and S4ΔaroD) and found that, across multiple vaccines, the %O-Ag dep Ab trended with vaccine efficacy. Among S4ΔguaBA-vaccinated Rbs, the %O-Ag dep Ab in pre-challenge plasma was significantly higher in survivors than in non-survivors; a cut-off of >70% O-Ag dep Ab predicted survival with high sensitivity and specificity. Finally, we found this COP in 80% of LVS-vaccinated Hu plasma samples as expected for a vaccine with 80% Hu efficacy. Collectively, the %O-Ag dep Ab response is a bona fide COP for S4ΔguaBA-vaccinated Rb and holds significant promise for guiding vaccine trials with higher animals.

Responses of the crab Heterozius rotundifrons to heterospecific chemical alarm cues: phylogeny vs. ecological overlap.

The big-handed brachyuran crab Heterozius rotundifrons extends the time spent in its anti-predator posture, limb extended posture, if exposed to chemical cues from crushed conspecifics. In this study, we tested whether crabs also respond to chemical cues from crushed heterospecific crabs, and if so, whether phylogenetic relations or ecological overlap is more important in influencing the duration of the anti-predator posture. Chemical cues from two other brachyuran crabs (Cyclograpsus lavauxi and Hemigrapsus sexdentatus), which do not overlap directly in ecological distribution with H. rotundifrons, elicited a duration of the anti-predator posture that was indistinguishable from that produced by conspecific chemical cues. In contrast, chemical cues from two anomuran crabs (Petrolisthes elongatus and Pagurus novizealandiae) that overlap in ecological distribution with H. rotundifrons, elicited durations of the antipredator posture that were significantly shorter than those of either conspecifics or more closely related crab species. Thus, phylogenetic relationship seems to be more important than ecological overlap in influencing anti-predator behavior in H. rotundifrons.