Rashedul Islam

Background: The dynamics of humoral immune responses following primary and booster COVID-19 vaccinations are crucial to understand in order to optimize vaccination strategies. This study evaluates the magnitude and durability of SARS-CoV-2-specific IgG antibody responses across different vaccines in a large cohort of Bangladeshi adults. Methods: A total of 6300 adults from nine hospitals across eight divisions of Bangladesh were enrolled. Participants received two primary doses of either ChAdOx1 nCoV-19 (Covishield, Serum Institute of India, n = 2855), mRNA-1273 (Moderna, n = 578), BNT162b2 (Pfizer-BioNTech, n = 121), or Vero-cell-inactivated (Sinopharm, n = 2746) vaccines. Booster doses were administered at one-year intervals post-primary vaccination. SARS-CoV-2 spike receptor-binding domain (RBD)-specific IgG antibody responses were measured by ELISA using serum from vaccinees at multiple time points after two primary and two booster doses. Results: A total of 3745 individuals received booster 1 (third dose), with 59% receiving heterologous boosters (a different vaccine regimen than the primary doses). Only 5.5% (n = 347) of participants received a second booster one year after the first booster (among them, 99% received BNT162b2). Our results suggest that heterologous boosters with the mRNA vaccine induced higher IgG levels than homologous boosters for individuals who received primary vaccination with adenovirus vector-based ChAdOx1 nCoV-19 or a Vero-cell-inactivated vaccine. However, in those who initially received the mRNA-based vaccine, both homologous and heterologous boosters produced comparable IgG responses. Among all vaccine types, booster immunization with the Vero-cell-inactivated vaccine induced the lowest antibody responses. Longitudinal analysis demonstrated significantly high IgG levels over the 12 months following the first booster (p < 0.0001); however, IgG levels declined significantly after the second booster dose (fourth dose). Conclusions: Heterologous boosting strategies, particularly those involving mRNA vaccines, elicit stronger and more sustained IgG responses compared to a homologous booster. However, antibody waning after the second booster highlights the need for continued monitoring and potential additional vaccine strategies.

Background: Both SARS-CoV-2 infection and COVID-19 vaccines elicit immunological responses. However, it is difficult to distinguish responses generated after vaccination versus natural infection.Methods: We investigated SARS-CoV-2 spike receptor-binding domain (RBD) and nucleocapsid-specific IgG and RBD specific IgG subclasses (IgG1, IgG2, IgG3 and IgG4) responses using ELISA in four different groups; (1) COVID-19 patients (n=39) with varying disease severity and (2) COVID-19 vaccinated individuals (n=24, both adenovirus/mRNA based) (3) vaccinated after infection (n=39) and (4) patients experienced breakthrough infection (n=14), in Bangladesh.Results: Both COVID-19 patients and vaccinees developed robust RBD-specific IgG responses. In contrast, nucleocapsid specific IgG responses were found in patients but not in vaccine recipients. A distinct IgG subclass antibody response was observed in COVID-19 patients compared to COVID-19-vaccinated individuals. Specifically, COVID-19 patients exhibited elevated levels of both IgG1 and IgG3, with IgG3 dominating in the early phase of infection (days 1-7) followed by a subsequent increase in IgG1. Conversely, COVID-19 vaccination predominantly induced IgG1 responses without a concurrent rise in IgG3. This effect was more evident when a significant rise of IgG1 but not IgG3 was observed in patients who received COVID-19 vaccines after 90 days of infection. However, following breakthrough infection, we observed an increase in both IgG1 and IgG3. All of these findings collectively indicate that COVID-19 vaccination predominantly induces IgG1, whereas natural infection can elicit responses in both IgG1 and IgG3 subclasses.Conclusion: The findings highlight RBD-specific IgG3 as well as nucleocapsid IgG as crucial markers for differentiating between vaccination and natural infection and suggest these assays have utility for longitudinal monitoring of vaccinations and for establishing SARS-CoV-2 correlates of protection.

Background: Understanding the characteristics of the humoral immune responses following COVID-19 vaccinations is crucial for refining vaccination strategies and predicting immune responses to emerging SARS-CoV-2 variants.Methods: A longitudinal analysis of SARS-CoV-2 spike receptor binding domain (RBD) specific IgG antibody responses, encompassing IgG subclasses IgG1, IgG2, IgG3, and IgG4 was performed. Participants received four mRNA vaccine doses (group 1; n=10) or two ChAdOx1 nCoV-19 and two mRNA booster doses (group 2; n=19) in Bangladesh over two years.Results: Findings demonstrate robust IgG responses after primary Covishield or mRNA doses; declining to baseline within six months. First mRNA booster restored and surpassed primary IgG responses but waned after six months. Surprisingly, a second mRNA booster did not increase IgG levels further. Comprehensive IgG subclass analysis showed primary Covishield/mRNA vaccination generated predominantly IgG1 responses with limited IgG2/IgG3, Remarkably, IgG4 responses exhibited a distinct pattern. IgG4 remained undetectable initially but increased extensively six months after the second mRNA dose, eventually replacing IgG1 after the 3rd/4th mRNA doses. Conversely, initial Covishield recipients lack IgG4, surged post-second mRNA booster. Notably, mRNA-vaccinated individuals displayed earlier, robust IgG4 levels post first mRNA booster versus Covishield counterparts. IgG1 to IgG4 ratios decreased with increasing doses, most pronounced with four mRNA doses. This study highlights IgG response kinetics, influenced by vaccine type and doses, impacting immunological tolerance and IgG4 induction, shaping future vaccination strategies.Conclusions: This study highlights the dynamics of IgG responses dependent on vaccine type and number of doses, leading to immunological tolerance and IgG4 induction, and shaping future vaccination strategies.

Acute coronary syndrome (ACS), a subcategory of cardiovascular diseases, has become a major cause of mortality and morbidity worldwide. Oxidative stress resulting from increased production of reactive oxygen species and decreased antioxidants plays a major role in the pathophysiology of ACS. This study evaluated the activities of certain oxidase and antioxidant enzymes in circulation and neutrophils to determine their roles in increased oxidative stress in patients with ACS. A total of 52 patients with ACS admitted in the coronary care unit of two tertiary hospitals and 52 healthy controls were enrolled. Blood samples were collected from all subjects, and various oxidase and antioxidant enzymes in neutrophils and circulation were assayed. The patients had significantly higher white blood cell and neutrophil counts than the controls. In patients, the mean (±SD) serum activities of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (12.83±6.6 U/L) and superoxidase dismutase (4.34±1.41 U/mL) were significantly higher than in the control group (4.88±3.03 U/L and 3.02±1.7 U/mL, respectively) while the catalase had significantly lower activities (33.36±13.16 U/mL vs. 63.98±31.86 U/mL). In neutrophils, the activities of myeloperoxidase, NADPH oxidase and catalase were significantly higher in ACS patients, while superoxidase dismutase was significantly lower. Further, significant positive correlations were found between activities of myeloperoxidase and catalase, and NADPH oxidase and superoxidase dismutase in neutrophils of ACS patients. These findings revealed that higher activities of myeloperoxidase and NADPH oxidase, both in serum and neutrophils, lead to increased oxidative stress and form the inflammatory basis of ACS, and the antioxidant enzymes combat the events.