Biology subjects

Ferrari, G.

Publications and source records attributed to Ferrari, G..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Germline-targeting HIV Envelope SOSIP immunization more frequently elicits broadly-neutralizing antibody precursor responses in infant compared to juvenile rhesus macaques

A vaccine capable of inducing broadly neutralizing antibodies (bnAbs) is essential for effective prevention against HIV in children and adolescents. Germline-targeting vaccine strategies aim to stimulate bnAb precursor B cells through carefully designed immunogens, such as the stabilized SOSIP trimers, which mimic native HIV envelope (Env) proteins while presenting key neutralizing epitopes to germline B cell receptors. Given the ability of children living with HIV to develop bnAbs earlier and at a higher frequency than adults, we compared the immunogenicity of a CD4 binding site (CD4bs) bnAb germline-targeting SOSIP trimer immunization strategy in infant (n = 5) and juvenile (n = 4) rhesus macaques (RMs). Animals received 3 doses of the germline-targeting BG505 GT1.1 immunogen, followed by 3 boosts of wild-type BG505 SOSIP, each adjuvanted with the TLR7/8 agonist, 3M-052-SE. After 1.5 years, the RMs were further boosted with a mixed clade B Env trimer nanoparticle to enhance heterologous virus neutralization responses. This germline-targeting strategy induced equivalent titers of neutralizing antibodies in both groups of RMs, yet the infants exhibited a higher magnitude of vaccine-specific IgG binding. Notably, after 3 doses of BG505 GT1.1 SOSIP, infants had higher BG505 GT1.1-specific IgD- B cells. Upon completion of the vaccine regimen, 4 of 5 infants developed a CD4bs bnAb precursor response detectable in serum compared to only 1 of 4 juveniles. Finally, administration of the mixed clade B nanoparticle was able to increase the breadth of antibody responses in 3 of 5 infants and 2 of 4 juveniles. These results suggest that immunization in early-life may enhance bnAb induction and highlight the potential for future pediatric HIV-1 vaccine strategies. Author SummaryVaccines that can generate antibody responses that have breadth and potency in neutralization can protect children and adolescents from acquiring multi-strain viruses like HIV. Increasingly, vaccine strategies have become better tailored to elicit these broadly neutralizing antibodies (bnAbs), such as the germline-targeting HIV envelope antigens, which have shown great promise. To determine if we could elicit protective antibody responses against HIV in early life, we immunized infant and juvenile monkeys using the same vaccine strategy. In this study, we found that while both infants and juveniles developed similar levels of antibodies that could neutralize HIV, the infants showed stronger antibody responses in several key areas. Moreso, infants developed the type of early antibody response that researchers believe is needed to eventually evolve into broadly neutralizing antibodies. These findings suggest that initiating HIV vaccination earlier in life may offer a better chance at generating the bnAbs needed to protect against various HIV strains. Our work highlights the potential benefits of initiating an HIV vaccine regimen in childhood.

immunology↗

bioRxiv2025

Chromosome-level genome assembly of Norwegian wild alpine reindeer (Rangifer tarandus tarandus)

We describe a chromosome-level genome assembly from a wild alpine reindeer individual (Rangifer tarandus tarandus) from the Rondane area in Southern Norway. The assembly is resolved into two pseudo-haplotypes: hap 1 spanning 3,081 megabases and hap 2 spanning 2,633 megabases. Contig N50 and scaffold N50 lengths are in the range of 31-41 Mb and 66-69 Mb, respectively. A large part of these two haplotypes (83.8% and 90.4%, respectively) are scaffolded into 34 autosomal chromosomal pseudomolecules, and in sex chromosomes X and Y for hap 1. The BUSCO completeness scores are 98.0% and 95.2%, respectively, and gene annotations of the assemblies identified 37,998 and 36,977 protein-coding genes. We also present an updated and improved genome assembly for Svalbard reindeer (Rangifer tarandus platyrhynchus) and a comparison with previously published genome assemblies of reindeer.

genomics↗

bioRxiv2024

A Comprehensive Engineering Strategy Improves Potency and Manufacturability of a Near Pan-neutralizing Antibody Against HIV

Anti-HIV envelope broadly neutralizing antibodies (bnAbs) are alternatives to conventional antiretrovirals with the potential to prevent and treat infection, reduce latent reservoirs, and/or mediate a functional cure. Clinical trials with "first generation" bnAbs used alone or in combination show promising antiviral effects but also highlight that additional engineering of "enhanced" antibodies will be required for optimal clinical utility, while preserving or enhancing cGMP manufacturing capability. Here we report the engineering of an anti-CD4 binding-site (CD4bs) bnAb, N49P9.3, purified from the plasma of an HIV elite-neutralizer. Through a series of rational modifications we produced a variant that demonstrates: enhanced potency; superior antiviral activity in combination with other bnAbs; low polyreactivity; and longer circulating half-life. Additional engineering for manufacturing produced a final variant, eN49P9, with properties conducive to cGMP production. Overall, these efforts demonstrate the feasibility of developing enhanced anti-CD4bs bnAbs with greatly improved antiviral properties as well as potential translational value.

bioengineering↗

bioRxiv2024

Bringing Attomolar Detection to the Point-of-Care with Nanopatterned DNA Origami Nanoantennas

Creating increasingly sensitive and cost-effective nucleic acid detection methods is critical for enhancing point-of-care (POC) applications. This involves capturing all desired biomarkers in a sample with high specificity and transducing the capture events to a detector. However, the signal from biomarkers present at extremely low amounts often falls below the detection limit of typical fluorescence-based methods, making molecular amplification a necessary step. Here, we present a nucleic acid detection assay of a 151-nucleotide sequence specific to antibiotics-resistant Klebsiella pneumoniae, based on single-molecule fluorescence detection of non-amplified DNA down to the attomolar level, using Trident NanoAntennas with Cleared HOtSpots (NACHOS). Our NACHOS-diagnostics assay leverages a compact microscope with a large field-of-view and cost-efficient components, including microfluidic flow to enhance capturing efficiency. Fluorescence enhancement is provided by DNA origami NanoAntennas, arranged in a dense array using a combination of nanosphere lithography and site-specific DNA origami placement. Our method can detect 200 {+/-} 50 out of 600 molecules in a 100 {micro}L sample volume within an hour. This represents typical number of pathogens in clinical samples commonly detected by Polymerase Chain Reaction but without the need for molecular amplification. We achieve similar sensitivity in untreated human blood plasma, enhancing the practical applicability of the system. Our platform can be adapted to detect shorter nucleic acid fragments that are not compatible with traditional amplification-based technologies. This broadens its potential for diverse diagnostic and healthcare applications, providing a robust and scalable solution for sensitive nucleic acid detection in various clinical settings.

biophysics↗

bioRxiv2024

A newly developed whole genome sequencing protocol enables early tracking of Enterovirus D68 molecular evolution.

Background Human enterovirus D68 (EV-D68) has been associated with an increase in mild-to-severe pediatric respiratory diseases worldwide. The rate of circulation of this virus is largely underestimated in the population and genetic evolutionary data are usually available only for partial sequences (e.g VP1 region). To achieve a timely genomic surveillance, a reliable, high-throughput EV-68 sequencing assay is required. Here we report an improved high-throughput EV-D68 whole-genome sequencing (WGS) assay performed directly on clinical samples that is suitable for short-read sequencing platforms. Between June and December 2022, a total 37 (1.9%) respiratory samples were EV-D68 positive and together with 52 additional samples with a median cycle threshold of 28.3, ranging from 18 to 36.8 were included in the validation analyses. Overall, all the primers had good performance and no mismatches were detected in more than 85% of sequences (932 WGS dataset). Using a cut-off of Cq <32 in at least 85.5% of samples a WG or PG was obtained, confirming an acceptable positive sequencing rate for the designed method. A total of 65 WGS were obtained and have a mean coverage of 98.4% across the genome, with a median depth of 6158x (range 2815x-7560x). Based on the obtained data, this method is cost effective resulting in an easy-to-perform protocol helpful for tracing the evolution of EV-D68 in protein different from VP1. EV-D68 could become a significant pathogen for public health in the next future, and thus this protocol for whole genome sequencing could help clinical and molecular virologists to be ready for molecular epidemiology surveillance.

microbiology↗

bioRxiv2024

Enhancing wheat yield potential through the QFFE.perg-5A and QFEm.perg-3A associated to spike fruiting efficiency: Insights from plot-level analysis

Wheat (Triticum aestivum L.) is a key global crop, essential for food security. To enhance its productivity this study focused on two quantitative trait loci (QTL), QFFE.perg-5A and QFEm.perg-3A, previously associated with fruiting efficiency at the spike level. We extended the analysis to the plot level to evaluate their impact on yield, thousand grain weight, and related traits, using a double haploid population of 102 lines in three environments. The results showed an epistatic interaction between a QTL for spike dry weight and grain number per spike. QFFE.perg-5A showed no interaction with the environment, increasing fruiting efficiency (13-15%), grain number per spike (7%), and spike number per unit area (9%), leading to an 8% rise in grain number per unit area and a 5% yield increase. In contrast, QFEm.perg-3As impact depended on the environment. This study connects spike-level QTL analysis with plot-level effects, providing valuable insights for breeding programs to improve wheat varieties with desirable traits and increased productivity.

genetics↗

bioRxiv2024

A high affinity monoclonal antibody against HLA-E-VL9 enhances natural killer cell anti-tumor killing

A major natural killer (NK) cell and CD8+ T cell checkpoint is mediated by the inhibitory receptor NKG2A/CD94 and its ligand, HLA-E complexed with 9 amino acid HLA-Ia leader sequence-derived peptides termed VL9 (HLA-E-VL9). Here, we used structure-based design and high throughput library screening to generate antibodies that block NKG2A/CD94 interactions, resulting in direct NK and CD8+ T cell cytotoxicity, and trigger NK cell antibody-dependent cellular cytotoxicity (ADCC). Anti-HLA-E-VL9 antibodies limited HLA-E-VL9+ tumor growth in mice, demonstrating checkpoint inhibition activity in vivo. HLA-E-VL9 was found to be expressed on HIV-infected cells, and its engagement by HLA-E-VL9 antibodies eliminated infected cells by NK-mediated ADCC. HLA-E-VL9 antibodies also enhanced the killing of HIV-infected cells by NKG2A/CD94+ CD8+ T cells targeting a novel HLA-E binding HIV Rev-derived epitope. Therefore, anti-HLA-E-VL9 antibodies represent a novel approach to eliminate pathogenic target cells by enhancing NK and CD8+ T cell function and promoting ADCC.

immunology↗

bioRxiv2024

Five millennia of mitochondrial introgression in Atlantic bluefin tuna identified using ancient DNA

Mitogenomic (MT) introgression between species is readily documented in marine fishes. Such introgression events may either be long-term natural phenomena or the result of human-driven shifts in spatial distributions of previously separated species. Determining the drivers behind MT introgression is stymied by the difficulty of directly observing patterns of interbreeding over long timescales. Using ancient DNA spanning five millennia, we here investigate the long-term presence of MT introgression from Pacific bluefin tuna (Thunnus orientalis) and albacore (Thunnus alalunga) into Atlantic bluefin tuna (Thunnus thynnus), a species with extensive exploitation history and observed shifts in abundance, and demographic distribution. Comparing ancient (n=130) and modern (n=78) mitogenomes of specimens covering most of the range of Atlantic bluefin tuna we detect no significant spatial or temporal population structure. This lack of spatiotemporal genomic differentiation is indicative of ongoing gene flow between populations and large effective population sizes over millennia. Moreover, we identify introgressed MT genomes in ancient specimens up to 5000 years old and find that this rate of introgression has remained similar through time. We therefore conclude that MT introgression in the Atlantic bluefin tuna is to date unaffected by anthropogenic impacts. By providing the oldest example of directly observed MT introgression in the marine environment, our results highlight the utility of ancient DNA to obtain temporal insights in the long-term persistence of such phenomena.

evolutionary biology↗

bioRxiv2024

Tracing 600 years of long-distance Atlantic cod trade in medieval and post-medieval Oslo using stable isotopes and ancient DNA

Marine resources have been important for the survival and economic development of coastal human communities across northern Europe for centuries. Knowledge of the origin of such historic resources can provide key insights into fishing practices and the spatial extent of trade networks. Here, we combine ancient DNA and stable isotopes ({delta}13C, {delta}15N, non-exchangeable {delta}2H and {delta}34S) to investigate the geographical origin of archaeological cod remains in Oslo from the eleventh to seventeenth centuries CE. Our findings provide genetic evidence that Atlantic cod was obtained from different sources, including a variety of distant-water populations like northern Norway and possibly Iceland. Evidence for such long-distance cod trade is already observed from the eleventh century, contrasting with archaeological and historical evidence from Britain and other areas of Continental Europe around the North and Baltic Seas, where such trade developed in a later period. Diverse biological origins are further supported by significant differences of a range of isotopes, indicating that multiple populations living in different environments were exploited. This research highlights the utility of combining ancient DNA methods and stable isotope analysis to describe the development of marine fisheries during the medieval and post-medieval period.

ecology↗

bioRxiv2023

Real-Time Structural Biology of DNA and DNA-Protein Complexes on an Optical Microscope

The intricate interplay between DNA and proteins is key for biological functions such as DNA replication, transcription, and repair. To better understand these interactions, it is crucial to develop tools to study DNA-protein complexes with high spatial and temporal resolution. Here, we use the vertical orientation that DNA adopts on graphene and investigate its interactions with proteins via energy transfer from a probe dye to graphene, achieving spatial resolution down to the [A]ngstrom scale. We measured the bending angle of DNA induced by adenine tracts, bulges, abasic sites and the binding of Escherichia coli endonuclease IV with unprecedented precision and millisecond time resolution. Additionally, we observed the translocation of the O6-alkylguanine DNA alkyltransferase along double-stranded DNA, reaching single-base pair resolution and detecting an affinity for adenine tracts. Overall, we foresee that this method will become a widespread tool for the dynamical study of nucleic acid and nucleic acid-protein interactions.

biophysics↗

bioRxiv2023

Germline-targeting SOSIP trimer immunization elicits precursor CD4 binding-site targeting broadly neutralizing antibodies in infant macaques.

A vaccine that can achieve protective immunity prior to sexual debut is critical to prevent the estimated 410,000 new HIV infections that occur yearly in adolescents. As children living with HIV can make broadly neutralizing antibody (bnAb) responses in plasma at a faster rate than adults, early childhood is an opportune window for implementation of a multi-dose HIV immunization strategy to elicit protective immunity prior to adolescence. Therefore, the goal of our study was to assess the ability of a B cell lineage-designed HIV envelope SOSIP to induce bnAbs in early life. Infant rhesus macaques (RMs) received either BG505 SOSIP or the germline-targeting BG505 GT1.1 SOSIP (n=5/group) with the 3M-052-SE adjuvant at 0, 6, and 12 weeks of age. All infant RMs were then boosted with the BG505 SOSIP at weeks 26, 52 and 78, mimicking a pediatric immunization schedule of multiple vaccine boosts within the first two years of life. Both immunization strategies induced durable, high magnitude binding antibodies and plasma autologous virus neutralization that primarily targeted the CD4-binding site (CD4bs) or C3/465 epitope. Notably, three BG505 GT1.1-immunized infants exhibited a plasma HIV neutralization signature reflective of VRC01-like CD4bs bnAb precursor development and heterologous virus neutralization. Finally, infant RMs developed precursor bnAb responses at a similar frequency to that of adult RMs receiving a similar immunization strategy. Thus, a multi-dose immunization regimen with bnAb lineage designed SOSIPs is a promising strategy for inducing protective HIV bnAb responses in childhood prior to adolescence when sexual HIV exposure risk begins.

immunology↗

bioRxiv2023

A novel HIV triple broadly neutralizing antibody (bNAb) combination-based passive immunization of infant rhesus macaques achieves durable protective plasma neutralization levels and mediates anti-viral effector functions.

To eliminate vertical HIV transmission and achieve therapy-free viral suppression among children living with HIV, novel strategies beyond antiretroviral therapy (ART) are necessary. Our group previously identified a triple bNAb combination comprising of 3BNC117, PGDM1400 and PGT151 that mediates robust in vitro neutralization and non-neutralizing effector functions against a cross-clade panel of simian human immunodeficiency viruses (SHIVs). In this study, we evaluated the safety, pharmacokinetics, and antiviral potency of this bNAb combination in infant rhesus macaques (RMs). We demonstrate that subcutaneous infusion of the triple bNAb regimen was well tolerated in pediatric monkeys and resulted in durable systemic and mucosal distribution. Plasma obtained from passively-immunized RMs demonstrated potent HIV-neutralizing and Fc-mediated antiviral effector functions. Finally, using the predicted serum neutralization 80% inhibitory dilution titer (PT80) biomarker, which was recently identified as a surrogate endpoint for evaluation of the preventative efficacy (PE) of bNAbs against mucosal viral acquisition in human clinical trials, we demonstrated that our regimen has a predicted PE[≥]90% against a large panel of plasma and breast milk-derived HIV strains and cross-clade SHIV variants. This data will guide the development of combination bNAbs for eliminating vertical HIV transmission and for achieving ART-free viral suppression among children living with HIV.

immunology↗

bioRxiv2023

Non-neutralizing SARS-CoV-2 N-terminal domain antibodies protect mice against severe disease using Fc-mediated effector functions

Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be non-neutralizing yet it protected mice and cynomolgus macaques from severe disease. The mechanisms of this non-neutralizing antibody-mediated protection are unknown. Here we show that Fc effector functions mediate non-neutralizing antibody (non-nAb) protection against SARS-CoV-2 MA10 viral challenge in mice. Though non-nAb infusion did not suppress infectious viral titers in the lung as potently as NTD neutralizing antibody (nAb) infusion, disease markers including gross lung discoloration were similar in nAb and non-nAb groups. Fc functional knockout substitutions abolished non-nAb protection and increased viral titers in the nAb group. Finally, Fc enhancement increased non-nAb protection relative to WT, supporting a positive association between Fc functionality and degree of protection in SARS-CoV-2 infection. This study demonstrates that non-nAbs can utilize Fc-mediated mechanisms to lower viral load and prevent lung damage due to coronavirus infection. AUTHOR SUMMARYCOVID-19 has claimed over 6.8 million lives worldwide and caused economic and social disruption globally. Preventing more deaths from COVID-19 is a principal goal of antibody biologic and vaccine developers. To guide design of such countermeasures, an understanding of how the immune system prevents severe COVID-19 disease is needed. We demonstrate here that antibody functions other than neutralization can contribute to protection from severe disease. Specifically, the functions of antibodies that rely on its Fc portion were shown to confer antibody-mediated protection of mice challenged with a mouse adapted version of SARS-CoV-2. Mice given an antibody that could not neutralize SARS-CoV-2 still showed a decrease in the amount of infectious virus in the lungs and less lung damage than mice given an irrelevant antibody. The decrease in infectious virus in the lungs was even larger when the non-neutralizing antibody was engineered to mediate non-neutralizing effector functions such as antibody-dependent cellular cytotoxicity more potently. Thus, in the absence of neutralization activity, non-neutralizing binding antibodies can contribute to the overall defense against SARS-CoV-2 infection and COVID-19 disease progression.

immunology↗

bioRxiv2022

Novel lentiviral vectors for gene therapy of sickle cell disease combining gene addition and gene silencing strategies

Sickle cell disease (SCD) is due to a mutation in the {beta}-globin (HBB) gene causing the production of the toxic sickle hemoglobin (HbS, a2{beta}S2). Transplantation of autologous hematopoietic stem/progenitor cells (HSPCs) transduced with lentiviral vectors (LVs) expressing an anti-sickling {beta}-globin ({beta}AS) is a promising treatment; however, it is only partially effective and patients still present elevated HbS levels. Here, we developed a bifunctional LV expressing {beta}AS3-globin and an artificial microRNA (amiR) specifically downregulating {beta}S-globin expression with the aim of reducing HbS levels and favoring {beta}AS3 incorporation into Hb tetramers. Efficient transduction of SCD HSPC by the bifunctional LV led to a substantial decrease of {beta}S-globin transcripts in HSPC-derived erythroid cells, a significant reduction of HbS+ red cells and effective correction of the sickling phenotype, outperforming {beta}AS gene addition and BCL11A gene silencing strategies. The bifunctional LV showed a standard integration profile and neither the HSPC viability, engraftment and multi-lineage differentiation nor the erythroid transcriptome and miRNAome were affected by the treatment, confirming the safety of this therapeutic strategy. In conclusion, the combination of gene addition and gene silencing strategies can improve the efficacy of current LV-based therapeutic approaches without increasing the mutagenic vector load, thus representing a novel treatment for SCD.

genetics↗

bioRxiv2022

Ancient DNA evidence for the ecological globalisation of cod fishing in medieval and post-medieval Europe

Understanding the historical emergence and growth of long-range fisheries can provide fundamental insights into the timing of ecological impacts and the development of coastal communities during the last millennium. Whole genome sequencing approaches can improve such understanding by determining the origin of archaeological fish specimens that may have been obtained from historic trade or distant water. Here, we used genome-wide data to individually infer the biological source of 37 ancient Atlantic cod specimens (ca. 1050 to 1950 CE) from England and Spain. Our findings provide novel genetic evidence that eleventh- to twelfth-century specimens from London were predominantly obtained from nearby populations, while thirteenth- to fourteenth-century specimens derived from distant sources. Our results further suggest that Icelandic cod was exported to London earlier than previously reported. Our observations confirm the chronology and geography of the trans-Atlantic cod trade from Newfoundland to Spain starting by the early sixteenth century. Our findings demonstrate the utility of whole genome sequencing and ancient DNA approaches to describe the globalisation of marine fisheries and increase our understanding regarding the extent of the North-Atlantic fish trade and long-range fisheries in medieval and early modern times.

ecology↗

bioRxiv2022

Food resources drive rodent population demography mediated by seasonality and inter-specific competition

O_LIAs fast reproducing species, rodents present proximate numerical responses to resource availability that have been assessed by experimental manipulation of food, with contrasting results. Other intrinsic and extrinsic factors, such as climate severity, species life cycles, and sympatry of potential competitors in the community, may interplay to modulate such responses, but their effects have rarely been evaluated ensemble. C_LIO_LIWe applied a niche-based approach to experimentally determine the effect of bottom-up (food availability) and top-down (climate severity) extrinsic factors, as well as intrinsic seasonal cycles, on rodent demography, also in presence of sympatry between species in the community. C_LIO_LITo this end, we live-trapped rodents at two latitudinal extremes of the boreal-temperate gradient (Italian Alps and Norway) deploying control/treatment designs of food manipulation. We applied a multistate open robust design model to estimate population patterns and survival rate. C_LIO_LIYellow-necked and wood mouse (Apodemus spp.) were sympatric with bank vole in Italy, while the latter was the only species trapped in Norway. At northern latitudes, where harsher climatic conditions occurred, vole survival was principally regulated by intrinsic seasonal cycles, with a positive effect of food also on population abundance. At southern latitudes, mice and voles exhibited asynchronous population patterns across seasons, with survival depending from seasonal cycles. When concentrated ad libitum food was experimentally provided, though, population size and survival of voles strongly decreased, while mice abundance benefited from food supplementation. C_LIO_LIOur results evidence that rodent demography is regulated by a combination of top-down (climate severity) and bottom-up (food availability) extrinsic factors, together with intrinsic seasonal ones. Moreover, we showed that the seasonal niche partitioning of mice and voles could be disrupted by availability of abundant resources that favour the demography of the more opportunistic Apodemus spp. at the expense of Myodes glareolus, suggesting competitive mechanisms. We conclude putting our results in the context of climate change, where shifts in vegetation productivity may affect the diversity of the rodent community via demographic effects. C_LI

ecology↗

bioRxiv2022

Inhibition of advanced glycation end product formation and serum protein infiltration in bioprosthetic heart valve leaflets: Investigations of anti-glycation agents.

Bioprosthetic heart valves (BHV) fabricated from glutaraldehyde pretreated heterograft tissue, such as bovine pericardium (BP) are the most commonly used heart valve replacements. However, BHV durability is limited by structural valve degeneration (SVD) resulting from both calcification and advanced glycation end product (AGE) deposition together with serum protein infiltration. In the present study we investigated the hypothesis that anti-AGE agents, Aminoguanidine (AG), Pyridoxamine (PYR), and N-Acetylcysteine (NAC) could mitigate AGE-serum protein mechanisms in model studies, both in vitro and in vivo, using rat subdermal implants of BP. In vitro studies demonstrated that each of these agents could significantly inhibit AGE formation in BP. However, in rat 28 days BP subdermal implants, only PYR demonstrated both significant inhibition of AGE and serum albumin accumulation per immunostaining. BHV calcification was not mitigated by PYR. It is concluded that AGE-serum protein pathophysiology contributing to SVD can be ameliorated by PYR.

biochemistry↗

bioRxiv2022

Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine

Coronavirus vaccines that are highly effective against SARS-CoV-2 variants are needed to control the current pandemic. We previously reported a receptor-binding domain (RBD) sortase A-conjugated ferritin nanoparticle (RBD-scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected monkeys from SARS-CoV-2 WA-1 infection. Here, we demonstrate SARS-CoV-2 RBD-scNP immunization induces potent neutralizing antibodies in non-human primates (NHPs) against all eight SARS-CoV-2 variants tested including the Beta, Delta, and Omicron variants. The Omicron variant was neutralized by RBD-scNP-induced serum antibodies with a mean of 10.6-fold reduction of ID50 titers compared to SARS-CoV-2 D614G. Immunization with RBD-scNPs protected NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protected mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect NHPs and mice from multiple different SARS-related viruses. Such a vaccine could provide the needed immunity to slow the spread of and reduce disease caused by SARS-CoV-2 variants such as Delta and Omicron.

immunology↗