Robust Response Research Articles

Positron emission tomography guided synergistic treatment of melanoma using multifunctional zirconium-hematoporphyrin nanosonosensitizers

Sonodynamic therapy (SDT) has emerged as a useful approach for tumor treatment. However, its widespread application is impeded by poor pharmacokinetics of existing sonosensitizers. Here we developed a metal-organic nanoplatform, wherein a small-molecule sonosensitizer (hematoporphyrin monomethyl ether, HMME) was ingeniously coordinated with zirconium, resulting in a multifunctional nanosonosensitizer termed Zr-HMME. Through post-synthetic modifications involving PEGylation and tumor-targeting peptide (F3) linkage, a nanoplatform capable of homing on melanoma was produced, which could elicit robust immune responses to suppress tumor lung metastasis in the host organism. Importantly, after seamless incorporation of positron-emitting 89Zr into this nanosonosensitizer, positron emission tomography (PET) could be used to monitor its in vivo pharmacokinetics. PET imaging studies revealed that this nanoplatform exhibited potent tumor accumulation and strong in vivo stability. Using intrinsic fluorescence from HMME, a dual-modal diagnostic capability (fluorescence and PET) was confirmed for this nanosonosensitizer. In addition, the mechanisms of how this nanoplatform interacted with immune system were also investigated. The collective data proved that the coordination structure between small-molecule drug cargos and metals may enhance the functions of each other while mitigating their weaknesses. This straightforward approach can expand the potential applications of suitable drug molecules.

A prospective humoral immune monitoring study of kidney transplant recipients receiving three doses of SARS-CoV-2 mRNA vaccine.

Kidney transplant recipients (KTRs), like other solid organ transplant recipients display a suboptimal response to mRNA vaccines, with only about half achieving seroconversion after two doses. However, the effectiveness of a booster dose, particularly in generating neutralizing antibodies (NAbs), remains poorly understood, as most studies have mainly focused on non-neutralizing antibodies. Here, we have longitudinally assessed the humoral response to the SARS-CoV-2 mRNA vaccine in 40 KTRs over a year, examining changes in both anti-spike IgG and NAbs following a booster dose administered about 5 months post-second dose. We found a significant humoral response increase 5 months post-booster, a stark contrast to the attenuated response observed after the second dose. Of note, nearly a quarter of participants did not achieve protective plasma levels even after the booster dose. We also found that the higher estimated glomerular filtration rate (eGFR) correlated with a more robust humoral response postvaccination. Altogether, these findings underscore the effectiveness of the booster dose in enhancing durable humoral immunity in KTRs, as evidenced by the protective level of NAbs found in 65% of the patients 5 months post- booster, especially those with higher eGFR rates.

Guardians of wheat: Unleashing transgenerational immune priming with Trichoderma against spot blotch

Plants encounter various biotic stresses in their natural habitat, prompting the exploration of innovative protective measures to bolster their immune defences against pathogens. An effective strategy involves priming plant immunity, conferring enduring and comprehensive protection. Defence priming, characterized by heightened responsiveness to attackers following prior stress exposure, intriguingly manifests transgenerationally, transmitting the memory of priming to subsequent plant generations. In our investigation, we delved into the phenomenon of transgenerational immune priming (TGIP) in wheat facilitated by Trichoderma, spanning from the parental generation (G0) to the grand progeny (G2) generation. Successful establishment of transgenerational priming in the G2 generation was achieved by initially priming the G0 generation of wheat with Trichoderma. To assess priming inheritance, seeds from the G1 generation were collected, and both primed and non-primed wheat plants' grand progeny (G2 generation) were cultivated in soil. Subsequent evaluation encompassed the disease phenotype, biochemical parameters, and yield-related traits of the G2 generation wheat when confronted with Bipolaris sorokiniana, the causal agent of spot blotch disease. Our analysis revealed that the G2 generation of primed wheat displayed superior protection against spot blotch compared to non-primed wheat. Biochemical studies indicated no activation of defensive responses in the absence of disease pressure in G2 wheat plants. However, upon pathogen challenge, the grand progeny of primed wheat exhibited a robust defence response, surpassing that of non-primed wheat. This targeted defence response enabled efficient resource utilization and mitigated yield penalties. Furthermore, under biotic stress conditions, the grand progeny of primed wheat exhibited enhanced yield parameters compared to non-primed wheat. Our findings provide conclusive evidence that Trichoderma-mediated priming against B. sorokiniana can be inherited successfully from the parental (G0) generation to the grand progeny (G2) generation of wheat. This study represents the initial documentation of Trichoderma-mediated TGIP in wheat against B. sorokiniana, holding significant promise for sustainable agriculture by offering an environmentally friendly alternative to chemical pesticides.

Effect of Creep, Fatigue and Random Vibration on the Integrity of Solder Joints in BGA Package

This study employs Finite Element Analysis (FEA) to investigate the effects of creep, fatigue, and random vibration on the integrity of solder joints in BGA packages in electronic modules. Evaluating the response of lead-based Sn63Pb37 and lead-free SnAgCu alloy solders (SAC305, SAC387, SAC396, and SAC405) to induced loads - stress, strain, strain energy density, and displacement in the joints is obtained and studied better to understand the mechanism of the joints' degradation. SAC305 and SAC405 are modelled with linear stress-temperature relationships σ = 3.152T–68.167 and σ = 1.543T–34.983, respectively. The magnitude of the strain energy density in the joints is a key failure driver. SAC387 and SAC396 solder joints display lower values of strain energy density and thus have higher durability. Displacement analysis indicates that SAC305 and Sn63Pb37 are prone to deformation-induced failure. SAC387 exhibits the highest fatigue yield stress at 58 MPa, while SAC405 displays the lowest stress at 22 MPa. Analysis of the results of random vibration shows that Sn63Pb37 developed the highest stress at 34.62 MPa and is thus susceptible to stress-induced failure. The robust stress, strain, and strain energy responses of SAC405 and SAC396 provide key insights into improving the mechanical reliability of future electronic devices towards better sustainability.

A facile and efficient voltammetric sensor for marbofloxacin detection based on zirconium-based metal-organic framework UiO-66/nitrogen-doped graphene nanocomposite

Improper and persistent use of marbofloxacin (MAR) is prone to produce residues that deteriorate the surrounding environment and endanger our health. Hence, it is urgent to stablish a facile and efficient detection technique for the detection of MAR. Herein, a highly efficient electrochemical platform was constructed for sensitive determination of MAR using zirconium-based metal–organic framework (UiO-66)/nitrogen-doped graphene (NG) nanocomposites (UiO-66/NG). The surface morphology, crystalline phase elemental composition, and electrochemical behavior of UiO-66/NG were characterized by various spectroscopic and electrochemical techniques. Owing to the synergistic interaction of UiO-66 MOFs and NG nanosheets, the UiO-66/NG exhibited remarkable catalytic activity for MAR oxidation. As consequently, the UiO-66/NG demonstrated a wide linear response range (0.01 − 10 μM), high sensitivity (1.80 μM μA−1 cm−2) and low detection limit (0.002 μM). The proposed UiO-66/NG/GCE demonstrated robust voltammetric responses even in the presence of excess potential interfering species and retained stable response signals for at least two weeks. More importantly, the proposed UiO-66/NG/GCE displayed highly consistent sensitivity toward MAR detection in both aquaculture water matrices and PBS buffer, and achieved accurate and sensitive detection of MAR with good recovery. Together with its low cost and facile operation, the UiO-66/NG/GCE shows great prospects for trace detection of MAR from complex matrices.

Intranasal Immunization for Zika in a Pre-Clinical Model

Humans continue to be at risk from the Zika virus. Although there have been significant research advancements regarding Zika, the absence of a vaccine or approved treatment poses further challenges for healthcare providers. In this study, we developed a microparticulate Zika vaccine using an inactivated whole Zika virus as the antigen that can be administered pain-free via intranasal (IN) immunization. These microparticles (MP) were formulated using a double emulsion method developed by our lab. We explored a prime dose and two-booster-dose vaccination strategy using MPL-A® and Alhydrogel® as adjuvants to further stimulate the immune response. MPL-A® induces a Th1-mediated immune response and Alhydrogel® (alum) induces a Th2-mediated immune response. There was a high recovery yield of MPs, less than 5 µm in size, and particle charge of −19.42 ± 0.66 mV. IN immunization of Zika MP vaccine and the adjuvanted Zika MP vaccine showed a robust humoral response as indicated by several antibodies (IgA, IgM, and IgG) and several IgG subtypes (IgG1, IgG2a, and IgG3). Vaccine MP elicited a balance Th1- and Th2-mediated immune response. Immune organs, such as the spleen and lymph nodes, exhibited a significant increase in CD4+ helper and CD8+ cytotoxic T-cell cellular response in both vaccine groups. Zika MP vaccine and adjuvanted Zika MP vaccine displayed a robust memory response (CD27 and CD45R) in the spleen and lymph nodes. Adjuvanted vaccine-induced higher Zika-specific intracellular cytokines than the unadjuvanted vaccine. Our results suggest that more than one dose or multiple doses may be necessary to achieve necessary immunological responses. Compared to unvaccinated mice, the Zika vaccine MP and adjuvanted MP vaccine when administered via intranasal route demonstrated robust humoral, cellular, and memory responses. In this pre-clinical study, we established a pain-free microparticulate Zika vaccine that produced a significant immune response when administered intranasally.

Characterization and application of recombinant Bovine Leukemia Virus Env protein

The Bovine Leukemia Virus (BLV) Envelope (Env) glycoprotein complex is instrumental in viral infectivity and shapes the host’s immune response. This study presents the production and characterization of a soluble furin-mutated BLV Env ectodomain (sBLV-EnvFm) expressed in a stable S2 insect cell line. We purified a 63 kDa soluble protein, corresponding to the monomeric sBLV-EnvFm, which predominantly presented oligomannose and paucimannose N-glycans, with a high content of core fucose structures. Our results demonstrate that our recombinant protein can be recognized from specific antibodies in BLV infected cattle, suggesting its potential as a powerful diagnostic tool. Moreover, the robust humoral immune response it elicited in mice shows its potential contribution to the development of subunit-based vaccines against BLV.

Systems approach to design multi-epitopic peptide vaccine candidate against fowl adenovirus structural proteins for Gallus gallus domesticus

IntroductionFowl adenovirus (FAdV) is a significant pathogen in poultry, causing various diseases such as hepatitis-hydropericardium, inclusion body hepatitis, and gizzard erosion. Different serotypes of FAdV are associated with specific conditions, highlighting the need for targeted prevention strategies. Given the rising prevalence of FAdV-related diseases globally, effective vaccination and biosecurity measures are crucial. In this study, we explore the potential of structural proteins to design a multi-epitope vaccine targeting FAdV.MethodsWe employed an in silico approach to design the multi-epitope vaccine. Essential viral structural proteins, including hexon, penton, and fiber protein, were selected as vaccine targets. T-cell and B-cell epitopes binding to MHC-I and MHC-II molecules were predicted using computational methods. Molecular docking studies were conducted to validate the interaction of the multi-epitope vaccine candidate with chicken Toll-like receptors 2 and 5.ResultsOur in silico methodology successfully identified potential T-cell and B-cell epitopes within the selected viral structural proteins. Molecular docking studies revealed strong interactions between the multi-epitope vaccine candidate and chicken Toll-like receptors 2 and 5, indicating the structural integrity and immunogenic potential of the designed vaccine.DiscussionThe designed multi-epitope vaccine presents a promising approach for combating FAdV infections in chickens. By targeting essential viral structural proteins, the vaccine is expected to induce a robust immunological response. The in silico methodology utilized in this study provides a rapid and cost-effective means of vaccine design, offering insights into potential vaccine candidates before experimental validation. Future studies should focus on in vitro and in vivo evaluations to further assess the efficacy and safety of the proposed vaccine.

SARS-CoV-2-specific immune responses converge in kidney disease patients and controls with hybrid immunity

Healthy individuals with hybrid immunity, due to a SARS-CoV-2 infection prior to first vaccination, have stronger immune responses compared to those who were exclusively vaccinated. However, little is known about the characteristics of antibody, B- and T-cell responses in kidney disease patients with hybrid immunity. Here, we explored differences between kidney disease patients and controls with hybrid immunity after asymptomatic or mild coronavirus disease-2019 (COVID-19). We studied the kinetics, magnitude, breadth and phenotype of SARS-CoV-2-specific immune responses against primary mRNA-1273 vaccination in patients with chronic kidney disease or on dialysis, kidney transplant recipients, and controls with hybrid immunity. Although vaccination alone is less immunogenic in kidney disease patients, mRNA-1273 induced a robust immune response in patients with prior SARS-CoV-2 infection. In contrast, kidney disease patients with hybrid immunity develop SARS-CoV-2 antibody, B- and T-cell responses that are equally strong or stronger than controls. Phenotypic analysis showed that Spike (S)-specific B-cells varied between groups in lymph node-homing and memory phenotypes, yet S-specific T-cell responses were phenotypically consistent across groups. The heterogeneity amongst immune responses in hybrid immune kidney patients warrants further studies in larger cohorts to unravel markers of long-term protection that can be used for the design of targeted vaccine regimens.

Avoiding an emotions-action gap? The EU and genocide designations

ABSTRACT Genocide is one of the most heinous crimes perpetrated against humans. Violation of the norm against genocide should thus spark a robust response. Yet naming genocide is a highly contentious act, and the European Union and most of its member states have been cautious about using the term to describe atrocities. This article explores how the emotional resonance of the term ‘genocide’ inhibits its use by the EU, which in turn has implications for the EU’s response to purported genocidal violence. By not using the term, the EU avoids creating an emotions-action gap, as its actions are better aligned with the emotions it expresses through its rhetoric. But in so doing, the EU may also underestimate the potential for genocide and fail to take action to prevent it. In this way, emotions play a constraining role in the EU’s response to purported violations of the norm against genocide.

Three musketeers of PDA-based MRI contrasting and therapy

Polydopamine (PDA) stands as a versatile material explored in cancer nanomedicine for its unique properties, offering opportunities for multifunctional drug delivery platforms. This study explores the potential of utilizing a one-pot synthesis to concurrently integrate Fe, Gd and Mn ions into porous PDA-based theranostic drug delivery platforms called Ferritis, Gadolinis and Manganis, respectively. Our investigation spans the morphology, magnetic properties, photothermal characteristics and cytotoxicity profiles of those potent nanoformulations. The obtained structures showcase a spherical morphology, robust magnetic response and promising photothermal behaviour. All of the presented nanoparticles (NPs) display pronounced paramagnetism, revealing contrasting potential for MRI imaging. Relaxivity values, a key determinant of contrast efficacy, demonstrated competitive or superior performance compared to established, used contrasting agents. These nanoformulations also exhibited robust photothermal properties under near infra-red irradiation, showcasing their possible application for photothermal therapy of cancer. Our findings provide insights into the potential of metal-doped PDA NPs for cancer theranostics.

Distributionally Robust Demand Response for Heterogeneous Buildings with Rooftop Renewables under Cold Climates

Distributionally Robust Demand Response for Heterogeneous Buildings with Rooftop Renewables under Cold Climates

Fasting before Intra-Gastric Dosing with Antigen Improves Intestinal Humoral Responses in Syrian Hamsters

Oral vaccines, unlike injected, induce intestinal secretory immunoglobulin A (sIgA) mimicking our natural defense against gut pathogens. We previously observed sIgA responses after administering the Clostridioides difficile colonisation factor CD0873 orally in enteric capsules to hamsters. Enteric-coated capsules are designed to resist dissolution in the stomach and disintegrate only at the higher pH of the small intestine. However, the variable responses between animals led us to speculate suboptimal transit of antigens to the small intestine. The rate of gastric emptying is a controlling factor in the passage of oral drugs for subsequent availability in the small intestine for absorption. Whilst in humans, food delays gastric emptying, in rats, capsules can empty quicker from fed stomachs than from fasted. To test in hamsters if fasting improves the delivery of antigens to the small intestine, as inferred from the immune responses generated, 24 animals were dosed intragastrically with enteric capsules containing recombinant CD0873. Twelve hamsters were fasted for 12 h prior to each dose and the other 12 fed. Significantly higher sIgA titres, with significantly greater bacterial-adherence-blocking activity, were detected in small intestinal lavages in the fasted group. We conclude that fasting in hamsters improves intestinal delivery leading to more robust responses.

Enhancing the circular dichroism of chiral dielectric nanostructure through the addition of a symmetric Au cylinder

Abstract Circular dichroism (CD) spectra play a crucial role in recognition, separation and detection of chiral molecules. Due to the inherent weak CD response of natural chiral molecules, researchers have endeavored to enhance CD signals through various artificial nanostructures. In this study, combining the advantages of both the dielectric and metal materials, we propose a hybrid dielectric-metal nanostructure consisting of a chiral Si nanorod dimer coupled with a symmetric Au cylinder to achieve robust CD responses. Owing to the plasmon resonance of the Au cylinder, the scattering- and absorption-CD of the hybrid system have been enhanced, which result in the enhanced extinction CD response. Furthermore, the distributions of electric field, magnetic field and displacement current density of both the Si dimer and hybrid nanostructure have been meticulously crafted to elucidate the physical mechanisms underlying amplified CD signals. The synergistic coupling between the magnetic fields of dielectric materials and the electric fields of the Au cylinder leads to an increase in the electric field strength and the asymmetry of near-field distributions. Additionally, spatial overlaps between electric and magnetic fields occur. These factors contribute to the enhanced chiral response of the hybrid system. Meanwhile, the CD signal can be flexibly tuned by adjusting the size of the Au cylinder and Si nanorods. This design offers a versatile approach to enhancing the chiral response of dielectric nanostructures.

Safety and Immunogenicity of the Live Attenuated Varicella Vaccine in Vietnamese Children Aged 12 Months to 12 Years: An Open-Label, Single-Arm Bridging Study

Objective: This study aims to evaluate the safety and immunogenicity of the SKYVaricella vaccine in healthy Vietnamese children aged 12 months to 12 years. Methods: This open-label, single-arm study involved 201 children divided into two groups: 60 children aged 12 months to 5 years and 141 children aged 6 to 12 years. Safety was assessed through immediate reactions, solicited adverse events within 7 days, and unsolicited events up to Day 42. Immunogenicity was evaluated by seroconversion rates (SCR) and geometric mean titer (GMT) increments using fluorescent antibody-to-membrane antigen (FAMA) on the day of vaccination (D0) and 42 days after vaccination (D42). Results: All participants completed the follow-up. Immediate adverse events included pain (8.0%), redness (8.0%), and swelling (20.9%) at the injection site. Within 7 days, pain (17.9%) and swelling (12.4%) were mild and self-resolving. Unsolicited adverse events were infrequent and mild. Both age groups achieved 100% SCR. GMT of varicella-zoster virus antibodies increased from 1.37 (SD 1.97) at D0 to 18.02 (SD 2.22) at D42, a 13.12-fold rise. No Grade 3 adverse events were observed. Conclusion: The SKYVaricella vaccine shows a robust immunogenic response and favorable safety profile in Vietnamese children aged 12 months to 12 years. These findings endorse its potential inclusion in pediatric vaccination programs as a reliable preventive option against varicella.

A chemically induced attenuated strain of Candida albicans generates robust protective immune responses and prevents systemic candidiasis development

Despite current antifungal therapy, invasive candidiasis causes >40% mortality in immunocompromised individuals. Therefore, developing an antifungal vaccine is a priority. Here, we could for the first time successfully attenuate the virulence of Candida albicans by treating it with a fungistatic dosage of EDTA and demonstrate it to be a potential live whole cell vaccine by using murine models of systemic candidiasis. EDTA inhibited the growth and biofilm formation of C. albicans. RNA-seq analyses of EDTA-treated cells (CAET) revealed that genes mostly involved in metal homeostasis and ribosome biogenesis were up- and down-regulated, respectively. Consequently, a bulky cell wall with elevated levels of mannan and β-glucan, and reduced levels of total monosomes and polysomes were observed. CAET was eliminated faster than the untreated strain (Ca) as found by differential fungal burden in the vital organs of the mice. Higher monocytes, granulocytes, and platelet counts were detected in Ca- vs CAET-challenged mice. While hyper-inflammation and immunosuppression caused the killing of Ca-challenged mice, a critical balance of pro- and anti-inflammatory cytokines-mediated immune responses are the likely reasons for the protective immunity in CAET-infected mice.

Two-photon imaging of excitatory and inhibitory neural response to infrared neural stimulation.

Pulsed infrared neural stimulation (INS, 1875nm) is an emerging neurostimulation technology that delivers focal pulsed heat to activate functionally specific mesoscale networks and holds promise for clinical application. However, little is known about its effect on excitatory and inhibitory cell types in cerebral cortex. Estimates of summed population neuronal response time courses provide a potential basis for neural and hemodynamic signals described in other studies. Using two-photon calcium imaging in mouse somatosensory cortex, we have examined the effect of INS pulse train application on hSyn neurons and mDlx neurons tagged with GCaMP6s. We find that, in anesthetized mice, each INS pulse train reliably induces robust response in hSyn neurons exhibiting positive going responses. Surprisingly, mDlx neurons exhibit negative going responses. Quantification using the index of correlation illustrates responses are reproducible, intensity-dependent, and focal. Also, a contralateral activation is observed when INS applied. In sum, the population of neurons stimulated by INS includes both hSyn and mDlx neurons; within a range of stimulation intensities, this leads to overall excitation in the stimulated population, leading to the previously observed activations at distant post-synaptic sites.

Photosymbiont Density Is Correlated with Constitutive And Induced Immunity in The Facultatively Symbiotic Coral, Astrangia Poculata.

Scleractinian corals, essential ecosystem engineers that form the base of coral reef ecosystems, have faced unprecedented mortality in recent decades due to climate-change related stressors, including disease outbreaks. Despite this emergent threat to corals, many questions still remain regarding mechanisms underlying observed variation in disease susceptibility. Recent data suggests at least some degree of variation in disease response may be linked to variability in the relationship between host corals and their algal photosymbionts (Family Symbiodiniaceae). Still, the nuances of connections between symbiosis and immunity in cnidarians, including scleractinian corals, remain poorly understood. Here we leveraged an emergent model species, the facultatively symbiotic, temperate, scleractinian coral Astrangia poculata, to investigate associations between symbiont density and both constitutive and induced immunity. We used a combination of controlled immune challenges with heat-inactivated pathogens and transcriptomic analyses. Our results demonstrate that A. poculata mounts a robust initial response to pathogenic stimuli that is highly similar to responses documented in tropical corals. We document positive associations between symbiont density and both constitutive and induced immune responses, in agreement with recent preliminary studies in A. poculata. A suite of immune genes, including those coding for antioxidant peroxiredoxin biosynthesis, are positively associated with symbiont density in A. poculata under constitutive conditions. Furthermore, variation in symbiont density is associated with distinct patterns of immune response; low symbiont density corals induce preventative immune mechanisms whereas high symbiont density corals mobilize energetic resources to fuel humoral immune responses. In summary, our study reveals the need for more nuanced study of symbiosis-immune interplay across diverse scleractinian corals, preferably including quantitative energy budget analysis for full disentanglement of these complex associations and their effects on pathogen susceptibility.

Immunogenicity of 2 therapeutic mosaic HIV-1 vaccine strategies in individuals with HIV-1 on antiretroviral therapy

Mosaic HIV-1 vaccines have been shown to elicit robust humoral and cellular immune responses in people living with HIV-1 (PLWH), that had started antiretroviral therapy (ART) during acute infection. We evaluated the safety and immunogenicity of 2 mosaic vaccine regimens in virologically suppressed individuals that had initiated ART during the chronic phase of infection, exemplifying the majority of PLWH. In this double-blind, placebo-controlled phase 1 trial (IPCAVD013/HTX1002) 25 ART-suppressed PLWH were randomized to receive Ad26.Mos4.HIV/MVA-Mosaic (Ad26/MVA) (n = 10) or Ad26.Mos4.HIV/Ad26.Mos4.HIV plus adjuvanted gp140 protein (Ad26/Ad26+gp140) (n = 9) or placebo (n = 6). Primary endpoints included safety and tolerability and secondary endpoints included HIV-specific binding and neutralizing antibody titers and HIV-specific T cell responses. Both vaccine regimens were well tolerated with pain/tenderness at the injection site and fatigue, myalgia/chills and headache as the most commonly reported solicited local and grade 3 systemic adverse events, respectively. In the Ad26/Ad26+gp140 group, Env-specific IFN-γ T cell responses showed a median 12-fold increase while responses to Gag and Pol increased 1.8 and 2.4-fold, respectively. The breadth of T cell responses to individual peptide subpools increased from 11.0 pre-vaccination to 26.0 in the Ad26/Ad26+gp140 group and from 10.0 to 14.5 in the Ad26/MVA group. Ad26/Ad26+gp140 vaccination increased binding antibody titers against vaccine-matched clade C Env 5.5-fold as well as augmented neutralizing antibody titers against Clade C pseudovirus by 7.2-fold. Both vaccine regimens were immunogenic, while the addition of the protein boost resulted in additional T cell and augmented binding and neutralizing antibody titers. These data suggest that the Ad26/Ad26+gp140 regimen should be tested further.

#1474 COVID-19-infection in kidney transplant recipients during the omicron surge, a sigh of relief

Abstract Background and Aims The COVID-19 pandemic had a profound impact on global health, particularly affecting high-risk individuals such as solid organ transplant recipients (SOTRs). SOTRs have an elevated risk of severe COVID-19 disease and increased mortality. Kidney transplant recipients (KTRs) vaccinated with mRNA-based vaccines exhibit a lower response rate and shorter half-time of the serologic conversion. However, the percentage of serologic response improves with increasing number of vaccine doses. Studies also indicate that KTRs with prior COVID-19 infection demonstrate a more robust immune response post-immunization compared to COVID-19 naïve patients. Factors such as age, immunosuppressive regimen, eGFR, time since transplantation also impact vaccination response. This study aims to investigate COVID-19 infection outcome and vaccination response among KTRs during the Omicron surge. Method This study is a retrospective single-center cohort study at the Department of Nephrology and Transplantation at Skåne University Hospital in Malmö, Sweden. KTRs infected with COVID-19 during the Omicron surge were included (January 2022 until August 2023). Results 97 KTRs diagnosed with COVID-19 were included of whom 91 were vaccinated. In average, three doses of COVID-19-vaccine had been given to the patients. 67 KTRs showed seroconversion, 28 remained seronegative and the status of the remaining 2 KTRs was unknown. There was a significant association between lack of antibody production and mycophenolic acid (MPA) treatment (P = 0.019, Chi2 test), however the significance was not retained in a multivariate logistic regression analysis. Among the seroconverted (n = 67), 61 experienced mild infection, 5 moderate infection and 1 severe infection, according to the WHO clinical progression scale. In the seronegative group (n = 28), 25 had mild infection while the remaining three had moderate infection. The median time for viral clearance was examined in 79 KTRs and was 23 days (IQR 18-31). Immunosuppression was adjusted in 34% (n = 33) of cases. 2.1% (n = 2) of KTRs experienced graft rejection post infection. Conclusion While most patients experienced a mild infection, unlike during the first surges of the pandemic, the observed subsequent graft rejections emphasize the complexity of COVID-19´s potentially immunologic triggering effect and risk of graft loss in KTRs. The correlation between MPA treatment and a lower degree of serologic conversion after vaccination underscores the need for personalized immunologic follow up and treatment regimen in KTRs.