Publications by authors named "David A MacLeod"

The eradication of poliovirus remains a global health priority, with inactivated polio vaccines (IPVs) playing a pivotal role in immunization strategies. Over the past decades, advancements in IPV production have focused on optimizing safety, efficacy, and immunogenicity while addressing vaccine production and logistical challenges. This paper discusses a novel IPV candidate, IPV, which departs from conventional formalin inactivation and uses a modern ultraviolet C (UVC) inactivation technology that includes a powerful antioxidant that protects virus epitopes from damage during and after irradiation.

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Background/objective: Leishmaniasis is the second deadliest parasitic disease in the world, after malaria, with an estimated 1.6 million new cases each year. While cutaneous leishmaniasis can result in permanent scars from lesions after treatment, the mucocutaneous and visceral diseases can result in life-altering and life-threatening complications.

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Despite their efficacy, the currently available polio vaccines, oral polio vaccine (OPV) and inactivated polio vaccine (IPV), possess inherent flaws posing significant challenges in the global eradication of polio. OPV, which uses live Sabin attenuated strains, carries the risk of reversion to pathogenic forms and causing vaccine-associated paralytic poliomyelitis (VAPP) and vaccine-derived polio disease (VDPD) in incompletely vaccinated or immune-compromised individuals. Conventional IPVs, which are non-replicative, are more expensive to manufacture and introduce biohazard and biosecurity risks due to the use of neuropathogenic strains in production.

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causes multi-system diseases in both nosocomial settings and a pre-disposed general population. The bacterium is not only desiccation-resistant but also notoriously resistant to multiple antibiotics and drugs of last resort including carbapenem, colistin, and sulbactam. The World Health Organization has categorized carbapenem-resistant at the top of its critical pathogen list in a bid to direct urgent countermeasure development.

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Many microbes of concern to human health remain without vaccines. We have developed a whole-microbe inactivation technology that enables us to rapidly inactivate large quantities of a pathogen while retaining epitopes that were destroyed by previous inactivation methods. The method that we call UVC-MDP inactivation can be used to make whole-cell vaccines with increased potency.

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is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved.

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Based on skill estimates from hindcasts made over the last couple of decades, recent studies have suggested that considerable success has been achieved in forecasting winter climate anomalies over the Euro-Atlantic area using current-generation dynamical forecast models. However, previous-generation models had shown that forecasts of winter climate anomalies in the 1960s and 1970s were less successful than forecasts of the 1980s and 1990s. Given that the more recent decades have been dominated by the North Atlantic Oscillation (NAO) in its positive phase, it is important to know whether the performance of current models would be similarly skilful when tested over periods of a predominantly negative NAO.

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Background: Malaria presents public health challenge despite extensive intervention campaigns. A 30-year hindcast of the climatic suitability for malaria transmission in India is presented, using meteorological variables from a state of the art seasonal forecast model to drive a process-based, dynamic disease model.

Methods: The spatial distribution and seasonal cycles of temperature and precipitation from the forecast model are compared to three observationally-based meteorological datasets.

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Recent genome-wide association studies have linked common variants in the human genome to Parkinson's disease (PD) risk. Here we show that the consequences of variants at 2 such loci, PARK16 and LRRK2, are highly interrelated, both in terms of their broad impacts on human brain transcriptomes of unaffected carriers, and in terms of their associations with PD risk. Deficiency of the PARK16 locus gene RAB7L1 in primary rodent neurons, or of a RAB7L1 ortholog in Drosophila dopamine neurons, recapitulated degeneration observed with expression of a familial PD mutant form of LRRK2, whereas RAB7L1 overexpression rescued the LRRK2 mutant phenotypes.

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