ORCID Profile
0000-0002-4652-5609
Current Organisations
Australian National University
,
Monash University
,
University of Melbourne
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Publisher: Elsevier BV
Date: 12-2021
Publisher: Elsevier BV
Date: 02-2019
Publisher: Springer Science and Business Media LLC
Date: 21-01-2021
DOI: 10.1038/S41598-021-81389-Z
Abstract: The ferret is a key animal model for investigating the pathogenicity and transmissibility of important human viruses, and for the pre‐clinical assessment of vaccines. However, relatively little is known about the ferret immune system, due in part to a paucity of ferret‐reactive reagents. In particular, T follicular helper (Tfh) cells are critical in the generation of effective humoral responses in humans, mice and other animal models but to date it has not been possible to identify Tfh in ferrets. Here, we describe the screening and development of ferret-reactive BCL6, CXCR5 and PD-1 monoclonal antibodies. We found two commercial anti-BCL6 antibodies (clone K112-91 and clone IG191E/A8) had cross-reactivity with lymph node cells from influenza-infected ferrets. We next developed two murine monoclonal antibodies against ferret CXCR5 (clone feX5-C05) and PD-1 (clone fePD-CL1) using a single B cell PCR-based method. We were able to clearly identify Tfh cells in lymph nodes from influenza infected ferrets using these antibodies. The development of ferret Tfh marker antibodies and the identification of ferret Tfh cells will assist the evaluation of vaccine-induced Tfh responses in the ferret model and the design of novel vaccines against the infection of influenza and other viruses, including SARS-CoV2.
Publisher: Springer Science and Business Media LLC
Date: 13-07-2020
Publisher: Springer Science and Business Media LLC
Date: 17-09-2022
DOI: 10.1038/S41371-021-00609-1
Abstract: We assessed the association of hypertension with markers of inflammation and infection in a rural and disadvantaged Indian population. In a case-control study, we age- and gender-matched 300 cases with hypertension to 300 controls without hypertension. Blood pressure was measured according to a strict protocol. We measured markers of inflammation and infection including serum high-sensitivity C-reactive protein (hs-CRP), blood lymphocyte count, serum homocysteine, tooth loss, overcrowding and exposure to fecal contamination. Multivariable conditional logistic regression was used to determine their association with hypertension. Median serum hs-CRP was 42% greater in cases than controls, while median serum homocysteine was 10% greater. In multivariable conditional logistic regression, elevated homocysteine (OR 1.75, 95% CI 1.09-2.82), greater lymphocyte count (OR 1.49, 95% CI 1.01-2.01) and exposure to fecal contamination, defined as a distance from the field used for toilet purposes to the household of ≤50 m (OR 2.38, 95% CI 1.07-5.29), were independently associated with hypertension in this rural population. In separate analyses for each gender, elevated hs-CRP (OR 2.62, 95% CI 1.04-6.58) was associated with hypertension in men, whereas edentulism (OR 4.75, 95% CI 1.62-13.96) was associated with greater odds of hypertension in women. Our findings demonstrate specific associations between hypertension and markers of inflammation and infection including hs-CRP, homocysteine, lymphocyte count, edentulism and exposure to fecal contamination. Thus, strategies aimed at reducing inflammation and infection may reduce the burden of hypertension in such settings of disadvantage in rural India.
Publisher: American Chemical Society (ACS)
Date: 10-10-2019
Publisher: Wiley
Date: 25-06-2020
Publisher: Wiley
Date: 03-02-2020
Abstract: The conjugation of hydrophilic low-fouling polymers to therapeutic molecules and particles is an effective approach to improving their aqueous stability, solubility, and pharmacokinetics. Recent concerns over the immunogenicity of poly(ethylene glycol) has highlighted the importance of identifying alternative low fouling polymers. Now, a new class of synthetic water-soluble homo-fluoropolymers are reported with a sulfoxide side-chain structure. The incorporation of fluorine enables direct imaging of the homopolymer by
Publisher: Public Library of Science (PLoS)
Date: 02-11-2020
Publisher: Cold Spring Harbor Laboratory
Date: 10-09-2020
DOI: 10.1101/2020.09.09.20191205
Abstract: The durability of infection-induced SARS-CoV-2 immunity has major implications for public health mitigation and vaccine development. Animal studies 1,2 and the scarcity of confirmed re-infection 3 suggests immune protection is likely, although the durability of this protection is debated. Lasting immunity following acute viral infection requires maintenance of both serum antibody and antigen-specific memory B and T lymphocytes and is notoriously pathogen specific, ranging from life-long for smallpox or measles 4 , to highly transient for common cold coronaviruses (CCC) 5 . Neutralising antibody responses are a likely correlate of protective immunity and exclusively recognise the viral spike (S) protein, predominantly targeting the receptor binding domain (RBD) within the S1 sub-domain 6 . Multiple reports describe waning of S-specific antibodies in the first 2-3 months following infection 7-12 . However, extrapolation of early linear trends in decay might be overly pessimistic, with several groups reporting that serum neutralisation is stable over time in a proportion of convalescent subjects 8,12-17 . While SARS-CoV-2 specific B and T cell responses are readily induced by infection 6,13,18-24 , the longitudinal dynamics of these key memory populations remains poorly resolved. Here we comprehensively profiled antibody, B and T cell dynamics over time in a cohort recovered from mild-moderate COVID-19. We find that binding and neutralising antibody responses, together with in idual serum clonotypes, decay over the first 4 months post-infection, as expected, with a similar decline in S-specific CD4+ and circulating T follicular helper (cTFH) frequencies. In contrast, S-specific IgG+ memory B cells (MBC) consistently accumulate over time, eventually comprising a significant fraction of circulating MBC. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent subjects to 74 days, with probable additive protection from B and T cells. Overall, our study suggests SARS-CoV-2 immunity after infection is likely to be transiently protective at a population level. SARS-CoV-2 vaccines may require greater immunogenicity and durability than natural infection to drive long-term protection.
Publisher: Cold Spring Harbor Laboratory
Date: 18-05-2020
DOI: 10.1101/2020.05.11.20098459
Abstract: SARS-CoV-2, the pandemic coronavirus that causes COVID-19, has infected millions worldwide, causing unparalleled social and economic disruptions. COVID-19 results in higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive coronavirus immunological responses, induced by circulating human coronaviruses, is critical to understand such ergent clinical outcomes. The cross-reactivity of coronavirus antibody responses of healthy children (n=89), adults (n=98), elderly (n=57), and COVID-19 patients (n=19) were analysed by systems serology. While moderate levels of cross-reactive SARS-CoV-2 IgG, IgM, and IgA were detected in healthy in iduals, we identified serological signatures associated with SARS-CoV-2 antigen-specific Fcγ receptor binding, which accurately distinguished COVID-19 patients from healthy in iduals and suggested that SARS-CoV-2 induces qualitative changes to antibody Fc upon infection, enhancing Fcγ receptor engagement. Vastly different serological signatures were observed between healthy children and elderly, with markedly higher cross-reactive SARS-CoV-2 IgA and IgG observed in elderly, whereas children displayed elevated SARS-CoV-2 IgM, including receptor binding domain-specific IgM with higher avidity. These results suggest that less-experienced humoral immunity associated with higher IgM, as observed in children, may have the potential to induce more potent antibodies upon SARS-CoV-2 infection. These key insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.
Publisher: Cold Spring Harbor Laboratory
Date: 14-12-2020
DOI: 10.1101/2020.12.13.20248143
Abstract: The capacity of antibodies to engage with innate and adaptive immune cells via the Fc region is important in preventing and controlling many infectious diseases, and is likely critical in SARS-CoV-2 infection. The evolution of such antibodies during convalescence from COVID-19 is largely unknown. We developed novel assays to measure Fc-dependent antibody functions against SARS-CoV-2 spike (S)-expressing cells in serial s les from a cohort of 53 subjects primarily with mild-moderate COVID-19, out to a maximum of 149 days post-infection. We found that S-specific antibodies capable of engaging dimeric FcγRIIa and FcγRIIIa decayed linearly over time. S-specific antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP) activity within plasma declined linearly as well, in line with the decay of S-specific IgG. Although there was significant decay in S-specific plasma ADCC and ADP activity, they remained readily detectable by all assays in 94% of our cohort at the last timepoint studied, in contrast with neutralisation activity which was only detectable in 70% of our cohort by the last timepoint. Our results suggest that Fc effector functions such as ADCC and ADP could contribute to the durability of SARS-CoV-2 immunity, particularly late in convalescence when neutralising antibodies have waned. Understanding the protective potential of antibody Fc effector functions is critical for defining the durability of immunity generated by infection or vaccination.
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.JIM.2019.02.008
Abstract: Protective antibody (Ab) responses induced by natural infection or vaccination play a central role in defense against invasive pathogens. Germinal centers (GCs) are the sites of Ab affinity maturation and T follicular helper (Tfh) cells are a critical factor for driving GC formation and B cell selection. Therefore characterization of antigen (Ag)-specific Tfh cells is increasingly essential to define the mechanistic basis of protective antibody responses. However, since Tfh are weak producers of cytokines it is difficult to detect Ag-specific Tfh cells using conventional intracellular cytokine staining (ICS). Here, we report an assay identifying mouse Ag-specific Tfh cells by assessing the upregulation of surface activation-induced markers (AIM). Murine lymph node (LN)-derived Tfh cells largely retained CXCR5 and PD-1 expression following 18-hour cell culture. After influenza infection or influenza hemagglutinin (HA) protein vaccination of mice, stimulation of lymph node cell suspensions with peptide pools or whole protein drove upregulation of CD25, OX40 (CD134), ICOS (CD278) and CD154 on Tfh cells. Upregulation of either CD154 or CD25/OX40 proved a sensitive method for delineating HA-specific Tfh cells. This assay provides the opportunity to quantify antigen-specific Tfh cells in mice without the need for transgenic models or MHC-II tetramer reagents restricted to specific epitopes.
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.JENVMAN.2022.115917
Abstract: In this paper, we argue that current definitions of drought, especially in the context of small-scale agricultural production, are incomplete. We introduce the concept of 'technological drought' to account for crop failures, reduced yields or water scarcity, which are the consequence of an inability to supplement water when there is a lack of irrigation technology and/or existing poor water management. We illustrate the ersity of causes of technological drought, which can include shortages of fuel or electricity to operate pumps, problematically high costs to access irrigation infrastructure, or constrained access to pumps that have to be shared among multiple farmers. We argue that vulnerability to technological drought can be strongly conditioned by socio-economic conditions and that its impact can be magnified when population growth and the demand for food mean that any decline in yield can have serious consequences for food security. We show that technological drought is a complex phenomenon, and can be differentiated from the more widely-recognised classes of drought (meteorological, agricultural, hydrological, and socio-economic) in multiple ways. In particular, technological drought exhibits an important dependence on the socio-economic context of agricultural production. It is perhaps most evident in developing economies, especially where agricultural output depends strongly on the capacity of in idual farmers to manage crop water supply on small holdings. Technological drought can follow from even brief interruptions to monsoon rainfall during critical stages of crop growth, such that technological droughts can be distinguished from other forms of drought by their brevity.
Publisher: American Chemical Society (ACS)
Date: 13-07-2021
Publisher: American Chemical Society (ACS)
Date: 04-09-2019
Abstract: Nanoparticle-cell interactions between silica nanomaterials and mammalian cells have been investigated extensively in the context of drug delivery, diagnostics, and imaging. While there are also opportunities for applications in infectious disease, the interactions of silica nanoparticles with pathogenic microbes are relatively underexplored. To bridge this knowledge gap, here, we investigate the effects of organosilica nanoparticles of different sizes, concentrations, and surface coatings on surface association and viability of the major human fungal pathogen
Publisher: Cold Spring Harbor Laboratory
Date: 15-04-2023
DOI: 10.1101/2023.04.13.536825
Abstract: Long-lived plasma cells (PCs) secrete antibodies that can provide sustained immunity against infection. It has been proposed that high affinity cells are preferentially selected into this compartment, potentiating the immune response. Here we used single cell RNA-seq to track the development of Igh g2A10 cells, specific for the Plasmodium falciparum circumsporozoite protein ( Pf CSP) within the germinal center (GC). We identified cells differentiating into memory B cells (MBC) or PCs and estimated their affinity by V(D)J sequencing. While pre-memory cells were of lower affinity than GC B cells generally, the affinity of pre-PC cells was indistinguishable. Rather, a larger proportion of cells differentiated into PCs in waning GCs. These later emigrants replaced early arrivals in the bone marrow allowing the development of a high affinity PC compartment.
Publisher: American Chemical Society (ACS)
Date: 27-06-2022
Publisher: MDPI AG
Date: 29-09-2022
DOI: 10.3390/RS14194868
Abstract: Mangrove ecosystems provide critical goods and ecosystem services to coastal communities and contribute to climate change mitigation. Over four decades, remote sensing has proved its usefulness in monitoring mangrove ecosystems on a broad scale, over time, and at a lower cost than field observation. The increasing use of spectral indices has led to an expansion of the geographical context of mangrove studies from local-scale studies to intercontinental and global analyses over the past 20 years. In remote sensing, numerous spectral indices derived from multiple spectral bands of remotely sensed data have been developed and used for multiple studies on mangroves. In this paper, we review the range of spectral indices produced and utilised in mangrove remote sensing between 1996 and 2021. Our findings reveal that spectral indices have been used for a variety of mangrove aspects but excluded identification of mangrove species. The included aspects are mangrove extent, distribution, mangrove above ground parameters (e.g., carbon density, biomass, canopy height, and estimations of LAI), and changes to the aforementioned aspects over time. Normalised Difference Vegetation Index (NDVI) was found to be the most widely applied index in mangroves, used in 82% of the studies reviewed, followed by the Enhanced Vegetation Index (EVI) used in 28% of the studies. Development and application of potential indices for mangrove cover characterisation has increased (currently 6 indices are published), but NDVI remains the most popular index for mangrove remote sensing. Ultimately, we identify the limitations and gaps of current studies and suggest some future directions under the topic of spectral index application in connection to time series imagery and the fusion of optical sensors for mangrove studies in the digital era.
Publisher: Springer Science and Business Media LLC
Date: 19-02-2021
DOI: 10.1038/S41467-021-21444-5
Abstract: The durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with in idual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4 + and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG + memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.
Publisher: The American Association of Immunologists
Date: 15-05-2022
Abstract: Understanding the generation of immunity to SARS-CoV-2 in lymphoid tissues draining the site of infection has implications for immunity to SARS-CoV-2. We performed tonsil biopsies under local anesthesia in 19 subjects who had recovered from SARS-CoV-2 infection 24–225 d previously. The biopsies yielded & million cells for flow cytometric analysis in 17 subjects. Total and SARS-CoV-2 spike-specific germinal center B cells, and T follicular helper cells, were readily detectable in human tonsils early after SARS-CoV-2 infection, as assessed by flow cytometry. Responses were higher in s les within 2 mo of infection but still detectable in some subjects out to 7 mo following infection. We conclude the tonsils are a secondary lymphoid organ that develop germinal center responses to SARS-CoV-2 infection and could play a role in the long-term development of immunity.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 28-08-2230
DOI: 10.1126/SCIIMMUNOL.ABF5314
Abstract: Recent studies have established that memory B cells, largely thought to be circulatory in the blood, can take up long-term residency in inflamed tissues, analogous to widely described tissue-resident T cells. The dynamics of recruitment and retention of memory B cells to tissues and their immunological purpose remains unclear. Here, we characterized tissue-resident memory B cells (B RM ) that are stably maintained in the lungs of mice after pulmonary influenza infection. Influenza - specific B RM were localized within inducible bronchus-associated lymphoid tissues (iBALTs) and displayed transcriptional signatures distinct from classical memory B cells in the blood or spleen while showing partial overlap with memory B cells in lung-draining lymph nodes. We identified lung-resident markers, including elevated expression of CXCR3, CCR6, and CD69, on hemagglutinin (HA)– and nucleoprotein (NP)–specific lung B RM . We found that CCR6 facilitates increased recruitment and/or retention of B RM in lungs and differentiation into antibody-secreting cells upon recall. Although expression of CXCR3 and CCR6 was comparable in total and influenza-specific memory B cells isolated across tissues of human donors, CD69 expression was higher in memory B cells from lung and draining lymph nodes of human organ donors relative to splenic and PBMC-derived populations, indicating that mechanisms underpinning B RM localization may be evolutionarily conserved. Last, we demonstrate that human memory B cells in lungs are transcriptionally distinct to populations in lung-draining lymph nodes or PBMCs. These data suggest that B RM may constitute a discrete component of B cell immunity, positioned at the lung mucosa for rapid humoral response against respiratory viral infections.
Publisher: Cold Spring Harbor Laboratory
Date: 29-08-2020
DOI: 10.1101/2020.08.27.270975
Abstract: Characterisation of germinal centre B and T cell responses yields critical insights into vaccine immunogenicity. Non-human primates are a key pre-clinical animal model for human vaccine development, allowing both lymph node and circulating immune responses to be longitudinally s led for correlates of vaccine efficacy. However, patterns of vaccine antigen drainage via the lymphatics after intramuscular immunisation can be stochastic, driving uneven deposition between lymphoid sites, and between in idual lymph nodes within larger clusters. In order to improve the accurate isolation of antigen-exposed lymph nodes during biopsies and necropsies, we developed and validated a method for co-formulating candidate vaccines with tattoo ink, which allows for direct visual identification of vaccine-draining lymph nodes and evaluation of relevant antigen-specific B and T cell responses by flow cytometry. This approach improves the assessment of vaccine-induced immunity in highly relevant non-human primate models.
Publisher: Cold Spring Harbor Laboratory
Date: 21-05-2020
DOI: 10.1101/2020.05.17.20104869
Abstract: The rapid global spread of SARS-CoV-2 and resultant mortality and social disruption have highlighted the need to better understand coronavirus immunity to expedite vaccine development efforts. Multiple candidate vaccines, designed to elicit protective neutralising antibodies targeting the viral spike glycoprotein, are rapidly advancing to clinical trial. However, the immunogenic properties of the spike protein in humans are unresolved. To address this, we undertook an in-depth characterisation of humoral and cellular immunity against SARS-CoV-2 spike in humans following mild to moderate SARS-CoV-2 infection. We find serological antibody responses against spike are routinely elicited by infection and correlate with plasma neutralising activity and capacity to block ACE2/RBD interaction. Expanded populations of spike-specific memory B cells and circulating T follicular helper cells (cTFH) were detected within convalescent donors, while responses to the receptor binding domain (RBD) constitute a minor fraction. Using regression analysis, we find high plasma neutralisation activity was associated with increased spike-specific antibody, but notably also with the relative distribution of spike-specific cTFH subsets. Thus both qualitative and quantitative features of B and T cell immunity to spike constitute informative biomarkers of the protective potential of novel SARS-CoV-2 vaccines.
Publisher: Springer Science and Business Media LLC
Date: 04-2021
DOI: 10.1038/S41467-021-22236-7
Abstract: The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such ergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children ( n = 89), adults ( n = 98), elderly ( n = 57), and COVID-19 patients ( n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy in iduals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy in iduals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.
Publisher: American Chemical Society (ACS)
Date: 28-10-2020
Publisher: MDPI AG
Date: 15-06-2021
DOI: 10.3390/RS13122345
Abstract: Poplar looper (Apocheima cinerarius Erschoff) is a destructive insect infesting Euphrates or desert poplars (Populus euphratica) in Xinjiang, China. Since the late 1950s, it has been plaguing desert poplars in the Tarim Basin in Xinjiang and caused widespread damages. This paper presents an approach to the detection of poplar looper infestations on desert poplars and the assessment of the severity of the infestations using time-series MODIS NDVI data via the wavelet transform and discriminant analysis, using the middle and lower reaches of the Yerqiang River as a case study. We first applied the wavelet transform to the NDVI time series data in the period of 2009–2014 for the study area, which decomposed the data into a representation that shows detailed NDVI changes and trends as a function of time. This representation captures both intra- and inter-annual changes in the data, some of which characterise transient events. The decomposed components were then used to filter out details of the changes to create a smoothed NDVI time series that represent the phenology of healthy desert poplars. Next the subset of the original NDVI time series spanning the time period when the pest was active was extracted and added to the smoothed time series to generate a blended time series. The wavelet transform was applied again to decompose the blended time series to enhance and identify the changes in the data that may represent the signals of the pest infestations. Based on the litude of the enhanced pest infestation signals, a predictive model was developed via discriminant analysis to detect the pest infestation and assess its severity. The predictive model achieved a severity classification accuracy of 91.7% and 94.37% accuracy in detecting the time of the outbreak. The methodology presented in this paper provides a fast, precise, and practical method for monitoring pest outbreak in dense desert poplar forests, which can be used to support the surveillance and control of poplar looper infestations on desert poplars. It is of great significance to the conservation of the desert ecological environment.
Publisher: American Society for Clinical Investigation
Date: 21-05-2020
Publisher: Elsevier BV
Date: 06-2021
Publisher: Wiley
Date: 19-05-2020
Publisher: American Chemical Society (ACS)
Date: 18-04-2019
Abstract: Upon exposure to human blood, nanoengineered particles interact with a multitude of plasma components, resulting in the formation of a biomolecular corona. This corona modulates downstream biological responses, including recognition by and association with human immune cells. Considerable research effort has been directed toward the design of materials that can demonstrate a low affinity for various proteins (low-fouling materials) and materials that can exhibit low association with human immune cells (stealth materials). An implicit assumption common to bio-nano research is that nanoengineered particles that are low-fouling will also exhibit stealth. Herein, we investigated the link between the low-fouling properties of a particle and its propensity for stealth in whole human blood. High-fouling mesoporous silica (MS) particles and low-fouling zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) particles were synthesized, and their interaction with blood components was assessed before and after precoating with serum albumin, immunoglobulin G, or complement protein C1q. We performed an in-depth proteomics characterization of the biomolecular corona that both identifies specific proteins and measures their relative abundance. This was compared with observations from a whole blood association assay that identified with which cell type each particle system associates. PMPC-based particles displayed reduced association both with cells and with serum proteins compared with MS-based particles. Furthermore, the enrichment of specific proteins within the biomolecular corona was found to correlate with association with specific cell types. This study demonstrates how the low-fouling properties of a material are indicative of its stealth with respect to immune cell association.
Publisher: American Society for Clinical Investigation
Date: 22-01-2019
DOI: 10.1172/JCI123366
Publisher: Elsevier BV
Date: 10-2021
Publisher: Cold Spring Harbor Laboratory
Date: 02-09-2020
DOI: 10.1101/2020.09.01.278630
Abstract: SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assessed prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD was associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augmented neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines were comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.
Publisher: Cold Spring Harbor Laboratory
Date: 26-01-2021
DOI: 10.1101/2021.01.24.21250074
Abstract: Endemic human coronaviruses (hCoV) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T cell memory in adults. We quantified CD4 T cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2 uninfected in iduals. T cell responses were widespread within conventional memory and cTFH compartments but did not correlate with IgG titres. SARS-CoV-2 cross-reactive T cells were observed in 48% of participants and correlated with HKU1 memory. hCoV-specific T cells exhibited a CCR6 + central memory phenotype in the blood, but were enriched for frequency and CXCR3 expression in human lung draining lymph nodes. Overall, hCoV-specific humoral and cellular memory are independently maintained, with a shared phenotype existing among coronavirus-specific CD4 T cells. This understanding of endemic coronavirus immunity provides insight into the homeostatic maintenance of immune responses that are likely to be critical components of protection against SARS-CoV-2.
Publisher: The American Association of Immunologists
Date: 15-07-2021
Abstract: Characterization of germinal center B and T cell responses yields critical insights into vaccine immunogenicity. Nonhuman primates are a key preclinical animal model for human vaccine development, allowing both lymph node (LN) and circulating immune responses to be longitudinally s led for correlates of vaccine efficacy. However, patterns of vaccine Ag drainage via the lymphatics after i.m. immunization can be stochastic, driving uneven deposition between lymphoid sites and between in idual LN within larger clusters. To improve the accurate isolation of Ag-exposed LN during biopsies and necropsies, we developed and validated a method for coformulating candidate vaccines with tattoo ink in both mice and pigtail macaques. This method allowed for direct visual identification of vaccine-draining LN and evaluation of relevant Ag-specific B and T cell responses by flow cytometry. This approach is a significant advancement in improving the assessment of vaccine-induced immunity in highly relevant nonhuman primate models.
Publisher: Cold Spring Harbor Laboratory
Date: 10-01-2022
DOI: 10.1101/2022.01.08.22268953
Abstract: Humans commonly have low level antibodies to poly(ethylene) glycol (PEG) due to environmental exposure. Lipid nanoparticle (LNP) mRNA vaccines for SARS-CoV-2 contain small amounts of PEG but it is not known whether PEG antibodies are enhanced by vaccination and what their impact is on particle–immune cell interactions in human blood. We studied plasma from 130 adults receiving either the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) mRNA vaccines, or no SARS-CoV-2 vaccine for PEG-specific antibodies. Anti-PEG IgG was commonly detected prior to vaccination and was significantly boosted a mean of 13.1-fold (range 1.0 to 70.9) following mRNA-1273 vaccination and a mean of 1.78-fold (range 0.68 to 16.6) following BNT162b2 vaccination. Anti-PEG IgM increased 68.5-fold (range 0.9 to 377.1) and 2.64-fold (0.76 to 12.84) following mRNA-1273 and BNT162b2 vaccination, respectively. The rise in PEG-specific antibodies following mRNA-1273 vaccination was associated with a significant increase in the association of clinically relevant PEGylated LNPs with blood phagocytes ex vivo . PEG antibodies did not impact the SARS-CoV-2 specific neutralizing antibody response to vaccination. However, the elevated levels of vaccine-induced anti-PEG antibodies correlated with increased systemic reactogenicity following two doses of vaccination. We conclude that PEG-specific antibodies can be boosted by LNP mRNA-vaccination and that the rise in PEG-specific antibodies is associated with systemic reactogenicity and an increase of PEG particle–leukocyte association in human blood. The longer-term clinical impact of the increase in PEG-specific antibodies induced by lipid nanoparticle mRNA-vaccines should be monitored.
Publisher: Wiley
Date: 2021
DOI: 10.1002/CTI2.1264
Publisher: Springer Science and Business Media LLC
Date: 24-11-2020
Publisher: Springer Science and Business Media LLC
Date: 03-03-2021
DOI: 10.1038/S41467-021-21665-8
Abstract: SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.
Publisher: Wiley
Date: 09-03-2021
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Hannah Kelly.