A defined mechanistic correlate of protection against Plasmodium falciparum malaria in non-human primates.

Malaria vaccine design and prioritization has been hindered by the lack of a mechanistic correlate of protection. We previously demonstrated a strong association between protection and merozoite-neutralizing antibody responses following vaccination of non-human primates against Plasmodium falciparum reticulocyte binding protein homolog 5 (PfRH5). Here, we test the mechanism of protection. Using mutant human IgG1 Fc regions engineered not to engage complement or FcR-dependent effector mechanisms, we produce merozoite-neutralizing and non-neutralizing anti-PfRH5 chimeric monoclonal antibodies (mAbs) and perform a passive transfer-P. falciparum challenge study in Aotus nancymaae monkeys. At the highest dose tested, 6/6 animals given the neutralizing PfRH5-binding mAb c2AC7 survive the challenge without treatment, compared to 0/6 animals given non-neutralizing PfRH5-binding mAb c4BA7 and 0/6 animals given an isotype control mAb. Our results address the controversy regarding whether merozoite-neutralizing antibody can cause protection against P. falciparum blood-stage infections, and highlight the quantitative challenge of achieving such protection

Standardization of the antibody-dependent respiratory burst assay with human neutrophils and Plasmodium falciparum malaria

The assessment of naturally-acquired and vaccine-induced immunity to blood-stage Plasmodium falciparum malaria is of long-standing interest. However, the field has suffered from a paucity of in vitro assays that reproducibly measure the anti-parasitic activity induced by antibodies in conjunction with immune cells. Here we optimize the antibody-dependent respiratory burst (ADRB) assay, which assesses the ability of antibodies to activate the release of reactive oxygen species from human neutrophils in response to P. falciparum blood-stage parasites. We focus particularly on assay parameters affecting serum preparation and concentration, and importantly assess reproducibility. Our standardized protocol involves testing each serum sample in singlicate with three independent neutrophil donors, and indexing responses against a standard positive control of pooled hyper-immune Kenyan sera. The protocol can be used to quickly screen large cohorts of samples from individuals enrolled in immuno-epidemiological studies or clinical vaccine trials, and requires only 6 μL of serum per sample. Using a cohort of 86 samples, we show that malaria-exposed individuals induce higher ADRB activity than malaria-naïve individuals. The development of the ADRB assay complements the use of cell-independent assays in blood-stage malaria, such as the assay of growth inhibitory activity, and provides an important standardized cell-based assay in the field

Climate Change and Weeds of Cropping Systems

The impacts of weeds in cropping systems are diverse and costly. Direct expenditure on control and biosecurity measures costs society billions each year. Even with such heavy investment in prevention and control, weeds continue to reduce the quality and quantity of agricultural produce and represent a significant threat to global food production. The challenge of managing weeds in cropping systems is rendered increasingly complex given the diverse and unpredictable impacts of climate change on both weeds and crops. Atmospheric CO2, temperature and precipitation are key drivers of plant growth, and weeds, like all other plant species, will need to respond to climate change in order to survive. Weed species are by their very nature survivors, able to relocate, acclimate or adapt to changing environmental conditions, with genetic diversity that could confer a natural competitive advantage over crop species. Conversely, modern crops are the result of extensive and highly sophisticated breeding to improve their genetic potential to survive in challenging conditions, including herbicide application, limited soil moisture and high temperatures. Moreover, agricultural weeds evolve in highly managed environments, and management intervention through crop selection, crop planting strategies and weed control measures may exert stronger selection pressures on weed species relative to climate change. It is, however, reasonable to assert that evolution driven by management pressures could occur simultaneously to climate-driven adaptation. For this reason, even given the rapid advancement of increasingly sophisticated weed control technology, weed management now and in the future should be guided a sound understanding of evolutionary biology