Humoral and cellular immunity to SARS-CoV-2 following vaccination with non-mRNA vaccines in adolescent/young adults with cancer: A prospective cohort study.

BACKGROUND: Data on SARS-CoV-2 vaccine responsiveness in adolescent/young adult (AYA) cancer patients are sparse. The present study assessed humoral and cellular immune responses post-vaccination in this population. METHODS: In this prospective study, patients aged 12-30 years undergoing cancer therapy ("on therapy") and survivors ("off therapy") were recruited. Anti-receptor binding domain (RBD) protein IgG levels were measured at baseline, four weeks post-first vaccine dose (T1), and six weeks post-second dose (T2). Cellular immunity was assessed using activation-induced markers and intracellular cytokine staining in a patient subset. The primary outcome was to quantify humoral responses in both cohorts at T2 compared to baseline. Clinical predictors of log antibody titres at T2 were identified. RESULTS: Between April-December 2022, 118 patients were recruited of median age 15.4 years. Among them, 77 (65.2 %) were in the "on therapy" group, and 77 (65.2 %) had received the BBV152 vaccine. At baseline, 108 (91.5 %) patients were seropositive for anti-RBD antibody. The log anti-RBD titre rose from baseline to T2 (p-value = 0.001) in the whole cohort; this rise was significant from baseline-T1 (p-value < 0.001), but not from T1 to T2 (p-value = 0.842). A similar pattern was seen in the "on therapy" cohort. BECOV-2 vaccine was independently associated with higher log anti-RBD titres than BBV152 (regression coefficient: 0.41; 95 % CI: 0.10-0.73; p = 0.011). Cellular immune responses were similar in the "on-" and "off therapy" groups at the three time points. CONCLUSION: Among AYA cancer patients, a single non-mRNA vaccine dose confers robust hybrid humoral immunity with limited benefit from a second dose.

Proportion of B cell subsets and Nrf2 mediated redox regulation in systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is characterized by expansion of autoreactive lymphocytes and impaired management of oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) plays a significant role in maintaining the redox homeostasis of cell. The present study aims to investigate the frequency of peripheral B cell subsets and the redox regulation by Nrf2 in SLE patients with variable disease activity. For this, a total of forty (40) SLE patients and twenty (20) age and gender-matched healthy controls (HCs) were recruited where patients with SLEDAI < 6 were grouped as Inactive SLE (n = 20) and patients with SLEDAI ≥ 6 were grouped as Active SLE (n = 20). A proportion of peripheral B cell subsets, level of ROS and expression of Nrf2 and Keap1 were studied with the help of flow cytometry and multiplex cytokine bead assay was exploited to estimate the serological concentration of cytokines. The frequency of B cell subsets was significantly altered and correlated with SLEDAI score. Concentration of IFNα2, IFN-ß, BAFF, APRIL and IL-6 was also raised in active SLE patients. Moreover, the level of cytosolic ROS was universally decreased while mitochondrial ROS was increased in B cell subsets. The expression of Nrf2 and Keap1 (a negative regulator of Nrf2) was significantly increased in B cell subsets of SLE patients. Here, it has been demonstrated that the frequency of peripheral B cell subsets varies with modification in the SLE disease activity. The given data also demonstrated that the expression of Nrf2 is significantly heightened in B cell subsets to deal with free radical stress.

Altered oxidative stress markers in relation to T cells, NK cells & killer immunoglobulin receptors that are associated with disease activity in SLE patients.

Systemic Lupus Erythematosus is an autoimmune disease with symptoms pervasive to all organ systems. It affects more females as compared to males (in the ratio 9:1). Oxidative stress plays a major role in the pathogenesis of SLE and other autoimmune diseases. In order to understand the relationship between cell specific oxidative stress and the severity of SLE, this research study involving the estimation of intracellular ROS accumulation in T and NK cell was conducted on SLE patients of North Indian Population. At the same time, to estimate anti-oxidant defense, Keap1 and Nrf2 levels were estimated in these cell types. The relationship between the expression of Killer immunoglobulin receptors i.e., KIR2DL4 & KIR3DL1 and oxidative stress was also evaluated as these receptors are imperative for the function and self-tolerance of NK cells.Oxidative stress was raised along with Keap1 and Nrf2 in T and NK cell subsets in SLE patients. The expression of KIR2DL4 was raised and that of KIR3DL1 was reduced in the NK cells of patients. The intensity of change in expression and its significance varied among the subsets. Nrf2 expression was raised in these species against oxidative stress as the antioxidant defense mechanism pertaining to Keap1-Nrf2 pathway, but the adequacy of response needs to be understood in further studies. The expression of KIR2DL4 and KIR3DL1 varied among the patient and healthy controls and the expression of the latter was found to have a significant positive relationship with plasma Glutathione(reduced) concentration.