SARS-CoV-2-specific cellular and humoral immunity after bivalent BA.4/5 COVID-19-vaccination in previously infected and non-infected individuals.

Knowledge is limited as to how prior SARS-CoV-2 infection influences cellular and humoral immunity after booster-vaccination with bivalent BA.4/5-adapted mRNA-vaccines, and whether vaccine-induced immunity may indicate subsequent infection. In this observational study, individuals with prior infection (n = 64) showed higher vaccine-induced anti-spike IgG-antibodies and neutralizing titers, but the relative increase was significantly higher in non-infected individuals (n = 63). In general, both groups showed higher neutralizing activity towards the parental strain than towards Omicron-subvariants BA.1, BA.2 and BA.5. In contrast, CD4 or CD8 T cell levels towards spike from the parental strain and the Omicron-subvariants, and cytokine expression profiles were similar irrespective of prior infection. Breakthrough infections occurred more frequently among previously non-infected individuals, who had significantly lower vaccine-induced spike-specific neutralizing activity and CD4 T cell levels. In summary, we show that immunogenicity after BA.4/5-bivalent vaccination differs between individuals with and without prior infection. Moreover, our results may help to improve prediction of breakthrough infections.

Potent induction of humoral and cellular immunity after bivalent BA.4/5 mRNA vaccination in dialysis patients.

Knowledge on immunogenicity of the bivalent Omicron BA.4/5 vaccine in dialysis patients and the effect of a previous infection is limited. Therefore, vaccine-induced humoral and cellular immunity was analyzed in dialysis patients and immunocompetent controls with and without prior infection. In an observational study, 33 dialysis patients and 58 controls matched for age, sex and prior infection status were recruited. Specific IgG, neutralizing antibody activity and cellular immunity towards the spike-antigen from parental SARS-CoV-2 and Omicron-subvariants BA.1, BA.2 and BA.4/5 were analyzed before and 13-18 days after vaccination. The bivalent vaccine led to a significant induction of IgG, neutralizing titers, and specific CD4+ and CD8+ T-cell levels. Neutralizing activity towards the parental strain was higher than towards the Omicron-subvariants, whereas specific T-cell levels towards parental spike and Omicron-subvariants did not differ indicating substantial cross-reactivity. Dialysis patients with prior infection had significantly higher spike-specific CD4+ T-cell levels with lower CTLA-4 expression compared to infection-naive patients. When compared to controls, no differences were observed between infection-naive individuals. Among convalescent individuals, CD4+ T-cell levels were higher in patients and neutralizing antibodies were higher in controls. Vaccination was overall well tolerated in both dialysis patients and controls with significantly less adverse events among patients. In conclusion, our study did not provide any evidence for impaired immunogenicity of the bivalent Omicron BA.4/5 vaccine in dialysis patients. Unlike in controls, previous infection of patients was even associated with higher levels of spike-specific CD4+ T cells, which may reflect prolonged encounter with antigen during infection.

NVX-CoV2373-induced cellular and humoral immunity towards parental SARS-CoV-2 and VOCs compared to BNT162b2 and mRNA-1273-regimens.

BACKGROUND: The NVX-CoV2373-vaccine has recently been licensed, although knowledge on vaccine-induced humoral and cellular immunity towards the parental strain and variants of concern (VOCs) in comparison to mRNA-regimens is limited. METHODS: In this observational study, 66 individuals were recruited to compare immunogenicity and reactogenicity of NVX-CoV2373 with BNT162b2 or mRNA-1273. Vaccine-induced antibodies were analyzed using ELISA and neutralization assays, specific CD4 and CD8 T-cells were characterized based on intracellular cytokine staining using flow-cytometry after antigen-specific stimulation with parental spike or VOCs. RESULTS: Two doses of NVX-CoV2373 strongly induced anti-spike IgG, although IgG-levels were lower than after vaccination with BNT162b2 or mRNA-1273 (p = 0.006). Regardless of the vaccine and despite different IgG-levels, neutralizing activity towards VOCs was highest for Delta, followed by BA.2 and BA.1. The protein-based vaccine failed to induce any spike-specific CD8 T-cells which were detectable in 3/22 (14%) individuals only. In contrast, spike-specific CD4 T-cells were induced in 18/22 (82%) individuals, although their levels were lower (p<0.001), had lower CTLA-4 expression (p<0.0001) and comprised less multifunctional cells co-expressing IFNγ, TNFα and IL-2 (p = 0.0007). Unlike neutralizing antibodies, NVX-CoV2373-induced CD4 T-cells equally recognized all tested VOCs from Alpha to Omicron. In individuals with a history of infection, one dose of NVX-CoV2373 had similar immunogenicity as two doses in non-infected individuals. The vaccine was overall well tolerated. CONCLUSION: NVX-CoV2373 strongly induced spike-specific antibodies and CD4 T-cells, albeit at lower levels as mRNA-regimens. Cross-reactivity of CD4 T-cells towards the parental strain and all tested VOCs may hold promise to protect from severe disease.

Comparative immunogenicity and reactogenicity of heterologous ChAdOx1-nCoV-19-priming and BNT162b2 or mRNA-1273-boosting with homologous COVID-19 vaccine regimens.

Comparative analyses of the immunogenicity and reactogenicity of homologous and heterologous SARS-CoV-2 vaccine-regimens will inform optimized vaccine strategies. Here we analyze the humoral and cellular immune response following heterologous and homologous vaccination strategies in a convenience cohort of 331 healthy individuals. All regimens induce immunity to the vaccine antigen. Immunity after vaccination with ChAdOx1-nCoV-19 followed by either BNT162b2 (n = 66) or mRNA-1273 (n = 101) is equivalent to or more pronounced than homologous mRNA-regimens (n = 43 BNT162b2, n = 59 mRNA-1273) or homologous ChAdOx1-nCoV-19 vaccination (n = 62). We note highest levels of spike-specific CD8 T-cells following both heterologous regimens. Among mRNA-containing combinations, spike-specific CD4 T-cell levels in regimens including mRNA-1273 are higher than respective combinations with BNT162b2. Polyfunctional T-cell levels are highest in regimens based on ChAdOx1-nCoV-19-priming. All five regimens are well tolerated with most pronounced reactogenicity upon ChAdOx1-nCoV-19-priming, and ChAdOx1-nCoV-19/mRNA-1273-boosting. In conclusion, we present comparative analyses of immunogenicity and reactogenicity for heterologous vector/mRNA-boosting and homologous mRNA-regimens.

Functionalized Graphene Oxide with Chitosan for Dopamine Biosensing.

Detecting biological structures via a rapid and facile method has become a pronounced point of research. Dopamine (DA) detection is critical for the early diagnosis of a variety of neurological diseases/disorders. A study on the real-time optical detection of DA is described here using graphene oxide (GO) functionalized with chitosan (Cs). Hence, a computational model dependent on a high theoretical level density functional theory (DFT) using the B3LYP/LANL2DZ model is carried out to study the physical as well as electronic properties of the proposed interaction between GO functionalized with Cs and its interaction with DA. GO functionalized with a Cs biopolymer was verified as having much higher stability and reactivity. Moreover, the addition of DA to functionalized GO yields structures with the same stability and reactivity. This ensures that GO-Cs is a stable structure with a strong interaction with DA, which is energetically preferred. Molecular electrostatic potential (MESP) calculation maps indicated that the impact of an interaction between GO and Cs increases the number of electron clouds at the terminals, ensuring the great ability of this composite when interacting with DA. Hence, these calculations and experimental results support the feasibility of using GO functionalized with Cs as a DA biosensor.

Deacetylated cellulose acetate nanofibrous dressing loaded with chitosan/propolis nanoparticles for the effective treatment of burn wounds.

Every year, about 1 out of 9 get burnt in Egypt, with a mortality rate of 37%, and they suffer from physical disfigurement and trauma. For the treatment of second-degree burns, we aim at making a smart bandage provided with control of drug release (using chitosan nanoparticles) to enhance the healing process. This bandage is composed of natural materials; namely, cellulose acetate (CA), chitosan, and propolis (bee resin) as the loaded drug. Cellulose acetate nanofibers were deacetylated by NaOH after optimizing the reaction time and the concentration of NaOH solution, and the product was confirmed with FTIR analysis. Chitosan/propolis nanoparticles were prepared by ion gelation method with size ranging from 100 to 200 nm and a polydispersity index of 0.3. Chitosan/propolis nanoparticles were preloaded in the CA solution to ensure homogeneity. Loaded deacetylated cellulose nanofibers have shown the highest hydrophobicity measured by contact angle. Cytotoxicity of propolis and chitosan/propolis nanoparticles were tested and the experimental IC50 value was about 137.5 and 116.0 µg/mL, respectively, with p-value ≤0.001. In addition, chitosan/propolis nanoparticles loaded into cellulose nanofibers showed a cell viability of 89.46% in the cell viability test. In-vivo experiments showed that after 21 days of treatment with the loaded nanofibers repairing of epithelial cells, hair follicles and sebaceous glands in the skin of the burn wound were found in albino-mice model.

Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination.

Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (n = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.

DNA Hybridization on Chitosan-Functionalized Silicon Substrate.

The ability of DNA to capture oligonucleotide molecules in solution is of great importance in genetics, medical diagnostics, and drug discovery. The DNA hybridization event in which the probe, which is usually a single-stranded DNA (ssDNA) covalently immobilized on a functionalized surface, recognizes the complementary target and forms a stable duplex structure that is the basis of highly specific bio recognizing devices. In this computational study, molecular modeling and Quantitative Structure Activity Relationship (QSAR) calculations were utilized at PM3 level in order to evaluate the interaction of aldehyde ssDNA on chitosan-functionalized silicon substrate and the biological activity of the proposed compounds. Molecular modeling of ssDNA 5'-(TTCA) attached on chitosan- functionalized silicon dioxide substrate was carried out. Molecular modeling and QSAR calculations were utilized at MM3 level in order to evaluate the interaction of target DNA on DNA probe on chitosan-functionalized silicon substrate through hydrogen bonding and the biological activity of the proposed compounds.