The Role of Cellular Immunity in the Protective Efficacy of the SARS-CoV-2 Vaccines

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been approved for clinical use. SARS-CoV-2 neutralizing antibody titers after immunization are widely used as an evaluation indicator, and the roles of cellular immune responses in the protective efficacy of vaccines are rarely mentioned. However, therapeutic monoclonal neutralizing antibodies have shown limited efficacy in improving the outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19), suggesting a passive role of cellular immunity in SARS-CoV-2 vaccines. The synergistic effect of virus-specific humoral and cellular immune responses helps the host to fight against viral infection. In fact, it has been observed that the early appearance of specific T-cell responses is strongly correlated with mild symptoms of COVID-19 patients and that individuals with pre-existing SARS-CoV-2 nonstructural-protein-specific T cells are more resistant to SARS-CoV-2 infection. These findings suggest the important contribution of the cellular immune response to the fight against SARS-CoV-2 infection and severe COVID-19. Nowadays, new SARS-CoV-2 variants that can escape from the neutralization of antibodies are rapidly increasing. However, the epitopes of these variants recognized by T cells are largely preserved. Paying more attention to cellular immune responses may provide new instructions for designing effective vaccines for the prevention of severe disease induced by the break-through infection of new variants and the sequelae caused by virus latency. In this review, we deliberate on the role of cellular immunity against COVID-19 and summarize recent advances in the development of SARS-CoV-2 vaccines and the immune responses induced by vaccines to improve the design of new vaccines and immunization strategies

Stability studies on 12-(5'-8'-hydroxyquinolinic)methylene-1,4,7,10- tetraazacyclo tridecane-11,13-dione, 5- substituted 1,10-phenanthroline-copper(II) with Cu²⁺ or Co²⁺ binuclear mixed coordinated systems

1428-1432C-functionalized dioxotetraamine ligands L have been designed and synthesized through simple methods, and characterized by elemental analysis, IR, mass spectra and 1H NMR. The ligand contains two independent chelating groups. At 25.0±0.1oC, I=0.1 mol·dm-3 NaNO3, pH titration has been performed to study the stability properties of L-5-R-5,10-phenanthroline-Cu(II) with proton, copper(II) and cobalt(II). The ternary complexes have been shown to possess interesting properties due to the involvement of three chelating groups, 5-substituted- 1, 10-phenanthroline, 8- hydroxyquinoline and dioxotetraamine. In addition, potentiometric titrations have been performed to study the protonation of L-5-R- 1, 10-phenanthroline-Cu(II) (R=CH3,H,Cl,NO2) and their stability properties with copper(II) and cobalt(II). The results show that for Cu2+ and Co2+, 8-hydroxyquinoline is a strong chelating reagent than dioxytetraamine macrocycles. Using molecular mechanics (MM+) calculation, the stability of ternary mixed system on Co(II)L- S-substituted- 1, 10-phenanthroline-Cu(II) and Cu(II)-L-Ssubstituted-1, 10-phenanthroline-Cu(II) have been studied and compared with the coordination ability for different coordination sites and for different metal ions (Co(II) and Cu(II) at the same coordination site. The results obtained from calculation agree with the experimental results

Selective 15 N-labeling of the side-chain amide groups of asparagine and glutamine for applications in paramagnetic NMR spectroscopy

The side-chain amide groups of asparagine and glutamine play important roles in stabilizing the structural fold of proteins, participating in hydrogen-bonding networks and protein interactions. Selective 15N-labeling of side-chain amides, however, can b

Synthesis of 1, 10-phenanthroline tetradentate diamines and potentiometric determination of the formation constants of their complexes with manganese(II), cobalt(II), copper(II) and zinc(II)

763-767Six tetradentate ligands incorporating 1, 10-phenanthroline and two alkyl amino donors have been prepared. The structure of these ligands has been studied by elemental analysis, IR and 1H NMR. N,N'-diisopropyl - 1, 10-phenanthroline -2,9-dimethanamine has been analyzed by X-ray diffraction. The crystal of C20H28N4. 1. 8(NO3)-0.2(OH)-2(H2O) is monoclinic, space group P2 l/c , (a=7.6 12(2), b=15.182 (3), c=20.551 (4)Å, β=91.16(3)o, z=4, R = 0.060, Rw=0.062). The protonation constants and the formation constant s of complexes with dipositive ion(Mn2+, Co2+,Cu2+ and Zn2+) have been determined in aqueous solution by pH metric method. Steric effects and electron inductive effects on the stability of complexes have been discussed

Kinetic and equilibrium studies of the acid dissociation of the zinc(II) complexes of N,N' -dialkyl-1, 10-phenanthroline-2,9-dimethanamine ligands

430-433The complexation property and the acid dissociation kinetics of the zinc(II) complexes of N,N' -dialkyl-1, 10-phenanthroline-2,9-dimethanamine ligands have been studied using pH-metric and a stopped-flow spectrophotometer. In 3.3×10-3 ~1.2×10-2 mol dm-3 HCl (I=0.5 mol dm-3, HCl + NaCl), the dissociation rate follows the law kobs= kK'[H+]. The acid dissociation can be rationalized in terms of four-step kinetic process involving two rapid pre-equilibrium protonations and rate-determining cleavage of the Zn(II)-N(phenanthroline) bond. Steric effects on the stability of complexes and on the kinetic process have also been discussed

Synthesis and characterization of novel N-functionalized macrocyclic dioxotetraamines bearing 8-hydroxyquinoline and its metal complexes: Stability in aqueous solutions

793-798Novel 4-(5'-8'-hydroxyquinoline)methylene-1,4,7, 10-tetraazacyclotridecane- 11,13-dione ligand (L) has been synthesized by simple method, and characterized by elemental analyses, IR and 1H NMR. It has two chelating sites each able to react with a transition metal ion to form complexes. At 25.0 0.1oC, I = 0.1 mol/dm3 NaNO3, potentiometric titrations have been performed to determine the protonation of L-5-R-1, 10-phenanthroline-Cu(II) (R = CH3, H, Cl, NO2) and the stability constants of Cu(II) and Co(II). The results show that for Cu(II) and Co(II) complexes, 8- hydroxyquinoline is a stronger chelating reagent than tetraamine[13]ene macrocycles. Molecular mechanics (MM+) calculations have been performed to assess the stability of ternary mixed system on CO(II)- L-5-substituted-10, 10-phenanthrolineCu(II) and CU(II)-L-5-substituted-1,10-phenanthro line-Cu(II). The coordination ability for different coordination sites and for different metal ions (Co(II) and Cu(II) at the same sites have been compared. The calculated results agree with those obtained experimentally. </span

Kinetics and mechanism of acid dissociation of cobalt(II) complex of 1,10-phenanthroline tetradentate diamine ligands

2514-2517The dissociation kinetics of cobalt(II) complx of 1,10- phenanthroline tetradentate diamine ligands have been studied using a stopped- flow spectrophotometer in 6.6×10-3 ~0.5 mol. Dm-3 HCl (I=0.5 mol. Dm-3 HCl+NaCl) over a range of temperature. The dissociation rate follows the law kobs=kK2[H+]/(1+K2 [H+]). The acid-assisted dissociation can be rationalized in terms of a four-step kinetic process involving two rapid pre-equilibrium protonations and rate-determining cleavage of the Co(II)-N(phenanthroline) bond. The temperature dependence of the rate and equilibrium constants have been determined and the appropriate thermodynamic parameters obtained. Steric effects in the dissociation kinetics have been discussed and the linear relationship between ΔH≠ and ΔS≠ has been found

Magic angle spinning NMR structure determination of proteins from pseudocontact shifts

Magic angle spinning solid-state NMR is a unique technique to study atomic-resolution structure of biomacromolecules which resist crystallization or are too large to study by solution NMR techniques. However, difficulties in obtaining sufficient number o