A vector-based vaccine dose after three doses of mRNA-based COVID-19 vaccination does not substantially improve humoral SARS-CoV-2 immunity in renal transplant recipient
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ABSTRACT:
SUBMITTER: Roch T
PROVIDER: S-EPMC8806390 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Knowledge on the immunogenicity of vector-based and mRNA-vaccines in solid organ transplant recipients is limited. Therefore, SARS-CoV-2-specific T cells and antibodies were analyzed in 40 transplant recipients and 70 controls after homologous or heterologous vaccine-regimens. Plasmablasts and SARS-CoV-2-specific CD4 and CD8 T cells were quantified using flow cytometry. Specific antibodies were analyzed by ELISA and neutralization assay. The two vaccine types differed after the first vaccination, as IgG and neutralizing activity were more pronounced after mRNA priming (p = .0001 each), whereas CD4 and CD8 T cell levels were higher after vector priming (p = .009; p = .0001). All regimens were well tolerated, and SARS-CoV-2-specific antibodies and/or T cells after second vaccination were induced in 100% of controls and 70.6% of transplant recipients. Although antibody and T cell levels were lower in patients, heterologous vaccination led to the most pronounced induction of antibodies and CD4 T cells. Plasmablast numbers were significantly higher in controls and correlated with SARS-CoV-2-specific IgG- and T cell levels. While antibodies were only detected in 35.3% of patients, cellular immunity was more frequently found (64.7%) indicating that assessment of antibodies is insufficient to identify COVID-19-vaccine responders. In conclusion, heterologous vaccination seems promising in transplant recipients, and combined analysis of humoral and cellular immunity improves the identification of responders among immunocompromised individuals.
| S-EPMC8652989 | biostudies-literature
Project description:DNA vaccines induce broad immunity, which involves both humoral and strong cellular immunity, and can be rapidly designed for novel or evolving pathogens such as influenza. However, the humoral immunogenicity in humans and higher animals has been suboptimal compared with that of traditional vaccine approaches. We tested whether the emulsion-based and ?-tocopherol containing adjuvant Diluvac Forte® has the ability to enhance the immunogenicity of a naked DNA vaccine (i.e., plasmid DNA). As a model vaccine, we used plasmids encoding both a surface-exposed viral glycoprotein (hemagglutinin) and an internal non-glycosylated nucleoprotein in the Th1/Th2 balanced CB6F1 mouse model. The naked DNA (50 µg) was premixed at a 1:1 volume/volume ratio with Diluvac Forte®, an emulsion containing different concentrations of ?-tocopherol, the emulsion alone or endotoxin-free phosphate-buffered saline (PBS). The animals received 2 intracutaneous immunizations spaced 3 weeks apart. When combined with Diluvac Forte® or the emulsion containing ?-tocopherol, the DNA vaccine induced a more potent and balanced immunoglobulin G (IgG)1 and IgG2c response, and both IgG subclass responses were significantly enhanced by the adjuvant. The DNA vaccine also induced CD4+ and CD8+ vaccine-specific T cells; however, the adjuvant did not exert a significant impact. We concluded that the emulsion-based adjuvant Diluvac Forte® enhanced the immunogenicity of a naked DNA vaccine encoding influenza proteins and that the adjuvant constituent ?-tocopherol plays an important role in this immunogenicity. This induction of a potent and balanced humoral response without impairment of cellular immunity constitutes an important advancement toward effective DNA vaccines.
| S-EPMC5557247 | biostudies-literature
Project description:Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2, with BNT162b2 (trade name: Comirnaty) efficiently protecting individuals from COVID-19 across a broad age range. Still, it remains largely unknown how renal insufficiency and immunosuppressive medication affect development of vaccine-induced immunity. We therefore comprehensively analyzed humoral and cellular responses in kidney transplant recipients after the standard second vaccination dose. As opposed to all healthy vaccinees and the majority of hemodialysis patients, only 4 of 39 and 1 of 39 transplanted individuals showed IgA and IgG seroconversion at day 8 ± 1 after booster immunization, with minor changes until day 23 ± 5, respectively. Although most transplanted patients mounted spike-specific T helper cell responses, frequencies were significantly reduced compared with those in controls and dialysis patients and this was accompanied by a broad impairment in effector cytokine production, memory differentiation, and activation-related signatures. Spike-specific CD8+ T cell responses were less abundant than their CD4+ counterparts in healthy controls and hemodialysis patients and almost undetectable in transplant patients. Promotion of anti-HLA antibodies or acute rejection was not detected after vaccination. In summary, our data strongly suggest revised vaccination approaches in immunosuppressed patients, including individual immune monitoring for protection of this vulnerable group at risk of developing severe COVID-19.
| S-EPMC8279581 | biostudies-literature
Project description:IntroductionRepeated measles outbreaks in countries with relatively high vaccine coverage are mainly due to failure to vaccinate and importation; however, cases in immunized individuals exist raising questions about suboptimal measles vaccine-induced humoral immunity and/or waning immunity in a low measles-exposure environment.Areas coveredThe plaque reduction neutralization measurement of functional measles-specific antibodies correlates with protection is the gold standard in measles serology, but it does not assess cellular-immune or other parameters that may be associated with durable and/or protective immunity after vaccination. Additional correlates of protection and long-term immunity and new determinants/signatures of vaccine responsiveness such as specific CD46 and IFI44L genetic variants associated with neutralizing antibody titers after measles vaccination are under investigation. Current and future systems biology studies, coupled with new technology/assays and analytical approaches, will lead to an increasingly sophisticated understanding of measles vaccine-induced humoral immunity and will identify 'signatures' of protective and durable immune responses.Expert opinionThis will translate into the development of highly predictive assays of measles vaccine efficacy, effectiveness, and durability for prospective identification of potential low/non-responders and susceptible individuals who require additional vaccine doses. Such new advances may drive insights into the development of new/improved vaccine formulations and delivery systems.
| S-EPMC6413513 | biostudies-literature
Project description: Not available
| S-EPMC8731234 | biostudies-literature
Project description:Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10-20 years post vaccination. This contrasted with a comparator group of adults, ages 35-49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112-3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.
| S-EPMC5207489 | biostudies-literature
Project description:Sustained exposure of lymphoid tissues to vaccine antigens promotes humoral immunity, but traditional bolus immunizations lead to rapid antigen clearance. We describe a technology to tailor vaccine kinetics in a needle-free platform translatable to human immunization. Solid pyramidal microneedle (MN) arrays were fabricated with silk fibroin protein tips encapsulating a stabilized HIV envelope trimer immunogen and adjuvant, supported on a dissolving polymer base. Upon brief skin application, vaccine-loaded silk tips are implanted in the epidermis/upper dermis where they release vaccine over a time period determined by the crystallinity of the silk matrix. Following MN immunization in mice, Env trimer was released over 2 wk in the skin, correlating with increased germinal center (GC) B cell responses, a ∼1,300-fold increase in serum IgG titers and a 16-fold increase in bone marrow (BM) plasma cells compared with bolus immunization. Thus, implantable MNs provide a practical means to substantially enhance humoral immunity to subunit vaccines.
| S-EPMC6697788 | biostudies-literature
Project description:With the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), studies are describing cases of glomerulonephritis arising after vaccination. We present the first case of a kidney transplant patient who, after mRNA vaccination against SARS-CoV-2, developed nephrotic proteinuria and renal dysfunction, with a biopsy diagnostic of collapsing glomerulonephritis. No other triggers for this glomerulonephritis were identified. Antibodies against the spike protein were negative, but the patient developed a specific T-cell response. The close time between vaccination and the proteinuria suggests a possible determinant role of vaccination. We should be aware of nephropathies appearing after COVID-19 vaccination in kidney transplant recipients also.
| S-EPMC9267596 | biostudies-literature
Project description:BackgroundThe new kidney allocation system in the United States has introduced longevity matching, which gives priority to allocating the best quality organs to wait-listed candidates with the longest predicted survival for the efficient utilization of organs that are of limited availability. The estimated post-transplant survival (EPTS) score was developed in the United States to risk-stratify all wait-listed patients. However, prognostic indices used in Western countries were derived from data that may be different for Korea and do not necessarily reflect prognostic values for Korean deceased donor kidney transplantation. Prognostic indices for Korean wait-listed candidates therefore need to be developed from Korean data.MethodsWe analyzed 6,731 adult solitary kidney transplant patients for candidate risk prediction using the national data from the Korean Network for Organ Sharing (KONOS) and National Health Insurance Data Sharing Service (NHISS). Cox regression analysis was used to model the risk of patient death.ResultsThe Korean EPTS (K-EPTS) score was developed based on four recipient parameters (age, diabetes mellitus, hepatitis C virus, and duration of dialysis) that showed a significant association with post-transplant survival. K-EPTS scores showed good discrimination (C-statistics 0.690; 95% confidence interval, 0.666-0.715). Moreover, the ability of the K-EPTS score to discriminate patient survival was better than that of the EPTS according to the criteria of the United Network for Organ Sharing (US-EPTS) score (P<0.001).ConclusionsThe K-EPTS score, which was developed based on Korean national data, is expected to contribute to the assessment of recipient prognosis and efficient utilization of deceased donor kidneys.
| S-EPMC9235339 | biostudies-literature
Project description:This study aimed to identify gene expression markers shared between both influenza hemagglutination inhibition (HAI) and virus-neutralization antibody (VNA) responses. We enrolled 158 older subjects who received the 2010-2011 trivalent inactivated influenza vaccine. Influenza-specific HAI and VNA titers and mRNA-sequencing were performed using blood samples obtained at Days 0, 3 and 28 post vaccination. For antibody response at Day 28 versus Day 0, several gene sets were identified as significant in predictive models for HAI (n=7) and VNA (n=35) responses. Five gene sets (comprising the genes MAZ, TTF, GSTM, RABGGTA, SMS, CA, IFNG and DOPEY) were in common for both HAI and VNA. For response at Day 28 versus Day 3, many gene sets were identified in predictive models for HAI (n=13) and VNA (n=41). Ten gene sets (comprising biologically related genes, such as MAN1B1, POLL, CEBPG, FOXP3, IL12A, TLR3, TLR7 and others) were shared between HAI and VNA. These identified gene sets demonstrated a high degree of network interactions and likelihood for functional relationships. Influenza-specific HAI and VNA responses demonstrated a remarkable degree of similarity. Although unique gene set signatures were identified for each humoral outcome, several gene sets were determined to be in common with both HAI and VNA response to influenza vaccine.
| S-EPMC5133148 | biostudies-literature