Denis Mamuli - Academia.edu (original) (raw)

Papers by Denis Mamuli

Molecular Pharmaceutics, Apr 11, 2016

Existing vaccines against human papillomavirus (HPV) require continuous cold-chain storage. Previ... more Existing vaccines against human papillomavirus (HPV) require continuous cold-chain storage. Previously, we developed a bacteriophage virus-like particle (VLP) based vaccine for Human Papillomavirus (HPV) infection, which elicits broadly neutralizing antibodies against diverse HPV types. Here, we formulated these VLPs into a thermostable dry powder using a multi-component excipient system and by optimizing the spray drying parameters using a half-factorial design approach. Dry powder VLPs were stable after spray drying and after long-term storage at elevated temperatures. Immunization of mice with a single dose of reconstituted dry powder VLPs that were stored at 37°C for more than a year elicited high anti-L2 IgG antibody titers. Spray dried thermostable, broadly protective L2 bacteriophage VLPs vaccine could be accessible to remote regions of the world (where ~84% of cervical cancer patients reside) by eliminating the cold-chain requirement during transportation and storage.

Molecular Pharmaceutics, 2016

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Jan 25, 2016

Formulating vaccines into a dry form enhances its thermal stability. This is critical to prevent ... more Formulating vaccines into a dry form enhances its thermal stability. This is critical to prevent administering damaged and ineffective vaccines, and to reduce its final cost. A number of vaccines in the market as well as those being evaluated in the clinical setting are in a dry solid state; yet none of these vaccines have achieved long-term stability at high temperatures. We used spray-drying to formulate a recombinant live attenuated Listeria monocytogenes (Lm; expressing Francisella tularensis immune protective antigen pathogenicity island protein IglC) bacterial vaccine into a thermostable dry powder using various sugars and an amino acid. Lm powder vaccine showed minimal loss in viability when stored for more than a year at ambient room temperature (∼23 °C) or for 180 days at 40 °C. High temperature viability was achieved by maintaining an inert atmosphere in the storage container and removing oxygen free radicals that damage bacterial membranes. Further, in vitro antigenicity ...

Applied and environmental microbiology, Jan 7, 2015

Freshwater scarcity and regulations on wastewater disposal have necessitated the reuse of treated... more Freshwater scarcity and regulations on wastewater disposal have necessitated the reuse of treated wastewater (TWW) for soil irrigation, which has several environmental and economic benefits. However, TWW irrigation can cause nutrient loading to the receiving environments. We assessed bacterial community structure and associated biogeochemical changes in soil plots irrigated with nitrate-rich TWW (referred to as pivots) for periods ranging from 13-30 years. Soil cores (0-40 cm) were collected in summer and winter from 5 irrigated pivots and 3 adjacently located non-irrigated plots. Total bacterial and denitrifier gene abundances were estimated by qPCR, and community structure was assessed by 454 massively parallel tag sequencing (MPTS) of SSU rRNA genes along with TRFLP of nirK, nirS and nosZ functional genes responsible for denitrification of the TWW associated nitrate. Soil physico-chemical analyses showed that, regardless of the seasons, pH and moisture contents (MC) were higher i...

Vaccine, 2015

An ideal prophylactic human papillomavirus (HPV) vaccine would provide broadly protective and lon... more An ideal prophylactic human papillomavirus (HPV) vaccine would provide broadly protective and long-lasting immune responses against all high-risk HPV types, would be effective after a single dose, and would be formulated in such a manner to allow for long-term storage without the necessity for refrigeration. We have developed candidate HPV vaccines consisting of bacteriophage virus-like particles (VLPs) that display a broadly neutralizing epitope derived from the HPV16 minor capsid protein, L2. Immunization with 16L2 VLPs elicited high titer and broadly cross-reactive and cross-neutralizing antibodies against diverse HPV types. In this study we introduce two refinements for our candidate vaccines, with an eye towards enhancing efficacy and clinical applicability in the developing world. First, we assessed the role of antigen dose and boosting on immunogenicity. Mice immunized with 16L2-MS2 VLPs at doses ranging from 2-25 μg with or without alum were highly immunogenic at all doses; alum appeared to have an adjuvant effect at the lowest dose. Although boosting enhanced antibody titers, even a single immunization could elicit strong and long-lasting antibody responses. We also developed a method to enhance vaccine stability. Using a spray dry apparatus and a combination of sugars & an amino acid as protein stabilizers, we generated dry powder vaccine formulations of our L2 VLPs. Spray drying of our L2 VLPs did not affect the integrity or immunogenicity of VLPs upon reconstitution. Spray dried VLPs were stable at room temperature and at 37°C for over one month and the VLPs were highly immunogenic. Taken together, these enhancements are designed to facilitate implementation of a next-generation VLP-based HPV vaccine which addresses U.S. and global disparities in vaccine affordability and access in rural/remote populations.

Genome Announcements, 2014

Bacteria associated with the Eastern oysters ( Crassostrea virginica ) native to Apalachicola Bay... more Bacteria associated with the Eastern oysters ( Crassostrea virginica ) native to Apalachicola Bay, FL, were investigated using 16S rRNA gene amplicon metagenomic sequencing which revealed that the oyster microbiome was predominated by Cyanobacteria and Proteobacteria . We also found that the oyster tissues were predominated by the pathogenic and symbiotic Photobacterium spp. (formerly known as Vibrio damsela e).

Microbial Ecology, 2012

Microorganisms are very sensitive to environmental change and can be used to gauge anthropogenic ... more Microorganisms are very sensitive to environmental change and can be used to gauge anthropogenic impacts and even predict restoration success of degraded environments. Here, we report assessment of bauxite mining activities on soil biogeochemistry and microbial community structure using unmined and three post-mined sites in Jamaica. The post-mined soils represent a chronosequence, undergoing restoration since 1987, 1997, and 2007. Soils were collected during dry and wet seasons and analyzed for pH, organic matter (OM), total carbon (TC), nitrogen (TN), and phosphorus. The microbial community structure was assessed through quantitative PCR and massively parallel bacterial ribosomal RNA (rRNA) gene sequencing. Edaphic factors and microbial community composition were analyzed using multivariate statistical approaches and revealed a significant, negative impact of mining on soil that persisted even after greater than 20 years of restoration. Seasonal fluctuations contributed to variation in measured soil properties and community composition, but they were minor in comparison to long-term effects of mining. In both seasons, post-mined soils were higher in pH but OM, TC, and TN decreased. Bacterial rRNA gene analyses demonstrated a general decrease in diversity in post-mined soils and up to a 3-log decrease in rRNA gene abundance. Community composition analyses demonstrated that bacteria from the Proteobacteria (α, β, γ, δ), Acidobacteria, and Firmicutes were abundant in all soils. The abundance of Firmicutes was elevated in newer post-mined soils relative to the un-mined soil, and this contrasted a decrease, relative to un-mined soils, in proteobacterial and acidobacterial rRNA gene abundances. Our study indicates long-lasting impacts of mining activities to soil biogeochemical and microbial properties with impending loss in soil productivity. Dawn E. Lewis and Ashvini Chauhan contributed equally to this work.

Microbial Ecology, 2009

Soil microorganisms are sensitive to environmental perturbations such that changes in microbial c... more Soil microorganisms are sensitive to environmental perturbations such that changes in microbial community structure and function can provide early signs of anthropogenic disturbances and even predict restoration success. We evaluated the bacterial functional diversity of un-mined and three chronosequence sites at various stages of rehabilitation (0, 10, and 20 years old) located in the Mocho Mountains of Jamaica. Samples were collected during the dry and wet seasons and analyzed for metal concentrations, microbial biomass carbon, bacterial numbers, and functional responses of soil microbiota using community-level physiological profile (CLPP) assays. Regardless of the season, un-mined soils consisted of higher microbial biomass and numbers than any of the rehabilitated sites. Additionally, the number and rate of substrates utilized and substrate evenness (the distribution of color development between the substrates) were significantly greater in the un-mined soils with carbohydrates being preferentially utilized than amino acids, polymers, carboxylic acids, and esters. To some extent, functional responses varied with the seasons but the least physiological activity was shown by the site rehabilitated in 1987 indicating long-term perturbation to this ecosystem. Small subunit ribosomal DNA (SSUrDNA)-denaturing gradientgel electrophoresis analyses on the microbiota collected from the most preferred CLPP substrates followed by taxonomic analyses showed Proteobacteria, specifically the gamma-proteobacteria, as the most functionally active phyla, indicating a propensity of this phyla to out-compete other groups under the prevailing conditions. Additionally, multivariate statistical analyses, Shannon's diversity, and evenness indices, principal component analysis, biplot and un-weighted-pair-group method with arithmetic averages dendrograms further confirmed that un-mined sites were distinctly different from the rehabilitated soils.

Applied and Environmental Microbiology, 2014

The objective of this study was to characterize fungal communities in a subsurface environment co... more The objective of this study was to characterize fungal communities in a subsurface environment cocontaminated with uranium and nitrate at the watershed scale and to determine the potential contribution of fungi to contaminant transformation (nitrate attenuation). The abundance, distribution, and diversity of fungi in subsurface groundwater samples were determined using quantitative and semiquantitative molecular techniques, including quantitative PCR of eukaryotic small-subunit rRNA genes and pyrosequencing of fungal internal transcribed spacer (ITS) regions. Potential bacterial and fungal denitrification was assessed in sediment-groundwater slurries amended with antimicrobial compounds and in fungal pure cultures isolated from the subsurface. Our results demonstrate that subsurface fungal communities are dominated by members of the phylum Ascomycota , and a pronounced shift in fungal community composition occurs across the groundwater pH gradient at the field site, with lower diver...

The International Journal of Business & Management, 2021

The main purpose of the study was to investigate the impact of procurement strategy on public sec... more The main purpose of the study was to investigate the impact of procurement strategy on public sector procurement performance perceptions. Owing to the diversity of functions, the use of public funds by a purchasing body to purchase products, facilities, and works is known as public procurement. The study's basic objectives on a case study of Masinde Muliro University of Science and Technology were conducted to determine the impact of procurement strategy on user perceptions of procurement performance in the public sector. In this study, a descriptive research design was adopted. Employees of Masinde Muliro University of Science and Technology were the target population. The study employed a descriptive design. The target population consisted of 1157 employees from Masinde Muliro University of Science and Technology. To generate a sample size of 286 respondents, researchers utilized purposeful, simple random, and stratified sampling procedures. Data was collected using a questionnaire. This study employed the Cronbach alpha coefficient as an indicator of test instrument reliability, at a threshold of 0.7 and beyond. Construct validity and material validity were employed to allow structured modifications of the research instrument for the purpose of enhancement and refinement. The data received from the departments was descriptively analyzed using SPSS version 25 to determine how dependent and independent variables are related. Pearson correlation coefficient was used to evaluate the strength of the association between the dependent and independent variables (r). The metrics for measuring the institutions' performance was the quality of service to user departments' satisfaction. The study found out that procurement planning practices contribute significantly on user perception of performance in MMUST. This study recommends that the MMUST management should incorporate procurement planning in their operations to enhance performance.