Biology subjects

Gilmour, J.

Publications and source records attributed to Gilmour, J..

5 recordsLinked to original sources

bioRxiv2025

An early functional adaptive NK cell signature drives optimal CD8+ T-cell activation and predicts sustained HIV-1 viral control.

A better understanding of the immune responses associated with future viral control in humans during acute HIV-1 infection (AHI) is critical to inform vaccines and immune-based therapeutics. Natural killer (NK) cells and CD8+ T-cells are pivotal in antiviral defence, yet the dynamics and complementary roles of these effector subsets during AHI with different HIV-1 subtypes remain poorly understood. Access to a unique patient cohort recruited during and post-peak HIV-1 viral load with different HIV-1 subtypes and followed up longitudinally in the absence of antiretroviral therapy up to six years post estimated date of infection (EDI) provided a rare opportunity to fill this knowledge gap. Our data show an early expansion of Fc{varepsilon}R{gamma}-CD57+ NK cells with classical adaptive traits concomitant with an enhanced capacity for antibody-dependent cellular cytotoxicity (ADCC) and reactivity against HIV-1 antigens. This distinctive NK cell profile was more abundant in donors with subtype A infection compared to non-subtype A, partially driven by elevated pro-inflammatory cytokine levels and changes in the epigenetic landscape. The accumulation of adaptive NK cells during the first month of infection contributed to the optimal activation of CD8+ T-cells, promoting virus-specific responses. Notably, individuals with higher levels of Fc{varepsilon}R{gamma}-CD57+ adaptive NK cells during the first month of infection were more likely to exhibit long-term viral control in the absence of ART. These findings underscore the critical role of early, high-magnitude adaptive NK cell responses in CD8+ T-cell activation and subsequent immune control. This work provides novel insights into the correlates of protective immunity against HIV-1 infection, with implications for preventative or therapeutic vaccine strategies aimed at promoting adaptive NK cell responses. One Sentence SummaryEarly expansion of adaptive NK cells during acute HIV-1 infection promotes long-term viral control.

immunology↗

bioRxiv2022

Evolutionary responses of a reef-building coral to climate change at the end of the last glacial maximum

Climate change threatens the survival of coral reefs on a global scale, primarily through mass bleaching and mortality as a result of marine heatwaves. While these short-term effects are clear, predicting the fate of coral reefs over the coming century is a major challenge. One way to understand the longer-term effects of rapid climate change is to examine the response of coral populations to past climate shifts. Coastal and shallow-water marine ecosystems such as coral reefs have been reshaped many times by sea-level changes during the Pleistocene, yet, few studies have directly linked this with its consequences on population demographics, dispersal, and adaptation. Here we use powerful analytical techniques, afforded by haplotype phased whole-genomes, to establish such links for the reef-building coral, Acropora digitifera. We show that three genetically distinct populations are present in northwestern Australia, and that their rapid divergence since the last glacial maximum (LGM) can be explained by a combination of founder-effects and restricted gene flow. Signatures of selective sweeps, too strong to be explained by demographic history, are present in all three populations and overlap with genes that show different patterns of functional enrichment between inshore and offshore habitats. In contrast to rapid divergence in the host, we find that photosymbiont communities are largely undifferentiated between corals from all three locations, spanning almost 1000 km, indicating that selection on host genes and not acquisition of novel symbionts, has been the primary driver of adaptation for this species in northwestern Australia.

evolutionary biology↗

bioRxiv2021

Mechanisms of ecological divergence with gene flow in a reef-building coral on an isolated atoll in Western Australia

Understanding the mechanisms driving phenotypic variation in traits facing intensified selection from climate change is a crucial step in developing effective conservation and restoration initiatives. This is particularly true for reef-building corals, which are among the most vulnerable to climate change and are in dramatic decline globally. At the Rowley Shoals in Western Australia, the prominent reef flat becomes exposed on low tide and the stagnant water in the shallow atoll lagoons heats up, creating a natural laboratory for characterising the mechanisms that control phenotypic responses to different environments. We combined whole genome re-sequencing, common garden heat stress experiments, transcriptome-wide gene expression analyses, and symbiont metabarcoding to explore the mechanisms that facilitate survival in contrasting habitat conditions. Our data show that, despite high gene flow between habitats, spatially varying selection drives subtle shifts in allele frequencies at hundreds of loci. These changes were concentrated into several islands of divergence spanning hundreds of SNPs that showed strong linkage disequilibrium and were associated with a coordinated increase in minor allele frequencies in corals taken from the lagoon habitat, where the range of environmental conditions is greatest. Common garden heat stress assays showed individuals from the lagoon exhibited higher bleaching resistance than colonies from the reef slope, and RNAseq identified pronounced physiological differences between the corals from the two habitats, primarily associated with molecular pathways including cell signalling, ion transport and metabolism. Despite the pronounced physioloigical and environmental differences between habitats, metabarcoding of the Symbiodiniaceae ITS2 region revealed all colonies to be associated exclusively with the genus Cladocopium, with no detectable differences between habitats. This study contributes to the growing number of studies documenting the complex mechanisms that facilitate coral survival in extreme environments, and showcases the utility of combining multiple sequencing techniques to unravel complex climate-related traits.

genomics↗

bioRxiv2020

Utilizing Computational Machine Learning Tools to Understand Immunogenic Breadth in the Context of a CD8 T-Cell Mediated HIV Response

Predictive models are becoming more and more commonplace as tools for candidate antigen discovery to meet the challenges of enabling epitope mapping of cohorts with diverse HLA properties. Here we build on the concept of using two key parameters, diversity metric of the HLA profile of individuals within a population and consideration of sequence diversity in the context of an individuals CD8 T-cell immune repertoire to assess the HIV proteome for defined regions of immunogenicity. Using this approach, Analysis of HLA adaptation and functional immunogenicity data enabled the identification of regions within the proteome that offer significant conservation, HLA recognition within a population, low prevalence of HLA adaptation and demonstrated immunogenicity. We believe this unique and novel approach to vaccine design that, in combination with in vitro functional assays, offers a bespoke pipeline for expedited and rational CD8 T-cell vaccine design for HIV and potentially other pathogens with the potential for both global and local coverage.

immunology↗

bioRxiv2018

Performance of an IAVI-African Network of Clinical Research Laboratories in Standardized ELISpot and Peripheral Blood Mononuclear Cell Processing in Support of HIV Vaccine Clinical Trials

Immunological assays performed in different laboratories participating in multi-centre clinical trials must be standardized in order to generate comparable and reliable data. This entails standardized procedures for sample collection, processing, freezing and storage. The International AIDS Vaccine Initiative (IAVI) partnered with local institutions to establish Good Clinical Laboratory Practice (GCLP)-accredited laboratories to support clinical trials in Africa, Europe and Asia. Here we report on the performance of seven laboratories based in Africa and Europe in the interferon-gamma enzyme-linked immunospot (IFN-{gamma} ELISpot) assay and peripheral blood mononuclear cell (PBMC) processing over four years. Characterized frozen PBMC samples from 48 volunteer blood packs processed at a central laboratory were sent to participating laboratories. For each stimulus, there were 1751 assays performed over four years. 98% of these ELISpot data were within acceptable ranges with low responses to mock stimuli. There were no significant differences in ELISpot responses at five laboratories actively conducting immunological analyses in support of IAVI sponsored clinical trials or HIV research. In a separate study, 1,297 PBMC samples isolated from healthy HIV-1 negative participants in clinical trials of two prophylactic HIV vaccine candidates were analysed for PBMC yield from fresh blood and cell recovery and viability following freezing and thawing. 94 % and 96 % of samples had fresh PBMC viabilities and cell yields within the pre-defined acceptance criteria while for frozen PBMC, 99 % and 96 % of samples had acceptable viabilities and cell recoveries respectively, along with acceptable ELISpot responses in 95%. These findings demonstrate the competency of laboratories across different continents to generate comparable and reliable data in support of clinical trials.\n\nImportanceThere is a need for the establishment of an African network of laboratories to support large clinical trials across the continent to support and further the development of vaccine candidates against emerging infectious diseases such as Ebola, Zika and dengue viruses and the continued HIV-1 pandemic. This is particularly true in sub-Saharan Africa where the HIV-1 pandemic is most severe. In this report we have demonstrated by using standardized SOPs, training, equipment and reagents that GCLP-accredited clinical trial laboratories based in Africa and Europe can process clinical trial samples and maintain cell integrity and functionality demonstrated by IFN-{gamma} ELISpot testing, producing comparable and reliable data.

immunology↗