Comparing the B and T cell-mediated immune responses in patients with type 2 diabetes receiving mRNA or inactivated COVID-19 vaccines

Abstract

Acquiring protective immunity through vaccination is essential, especially for patients with type 2 diabetes who are vulnerable for adverse clinical outcomes during coronavirus disease 2019 (COVID-19) infection. Type 2 diabetes (T2D) is associated with immune dysfunction. Here, we evaluated the impact of T2D on the immunological responses induced by mRNA (BNT162b2) and inactivated (CoronaVac) vaccines, the two most commonly used COVID-19 vaccines. The study consisted of two parts. In Part 1, the sera titres of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) alpha receptor binding domain (RBD), their neutralizing capacity, and antigen-specific CD4+T and CD8+T cell responses at 3-6 months after vaccination were compared between BNT162b2 (n=60) and CoronaVac (n=50) vaccinees with or without T2D. Part 2 was a time-course study investigating the initial B and T cell responses induced by BNT162b2 among vaccinees (n=16) with or without T2D. Our data showed that T2D impaired both cellular and humoral immune responses induced by CoronaVac. For BNT162b2, T2D patients displayed a reduction in CD4+T-helper 1 (Th1) differentiation following their first dose. However, this initial defect was rectified by the second dose of BNT162b2, resulting in comparable levels of memory CD4+ and CD8+T cells, anti-RBD IgG, and neutralizing antibodies with healthy individuals at 3-6 months after vaccination. Hence, T2D influences the effectiveness of COVID-19 vaccines depending on their platform. Our findings provide a potential mechanism for the susceptibility of developing adverse outcomes observed in COVID-19 patients with T2D and received either CoronaVac or just one dose of BNT162b2.

Reduced antibody response to COVID-19 vaccine composed of inactivated SARS-CoV-2 in diabetic individuals

“…Anti-RBD IgG antibodies are proved to be neutralizing against SARS-CoV-2 (39,40). In the present study, 98.2% (55/56) and 96.4% (54/56) of the non-DM subjects showed anti-N/S IgG positive and anti-RBD positive, respectively after a full vaccination with two doses at an interval of 2-4 weeks (Table 1 and Figure 2), which is in agreement with the results in the clinical trials (33,34). Thus, our data in the present study added more evidence that the inactivated COVID-19 vaccine efficiently elicited the non-neutralizing (anti-N) as well as neutralizing (anti-RBD) antibodies.…”

“…Considering that the positive rate of anti-RBD IgG was 97% in the non-T2DM subjects based on the results of clinical trials ( 33 , 34 ) and assumed 80% in the T2DM patients, we calculated that 46 patients per group would be required, with a power of 80% and a type I error rate of 0.05, by using a χ 2 -test. On the basis of an expected dropout of 10%, we planned to enroll 52 subjects per group.…”

“…COVID-19 vaccines composed of inactivated SARS-CoV-2 have been demonstrated to be effective and are also widely used in the world ( 24 , 25 , 29 – 32 ). However, the immunogenicity of inactivated COVID-19 vaccine in diabetic patients is not very clear ( 33 ). The present study aims to evaluate the antibody response to the inactivated SARS-CoV-2 vaccine in this population.…”

Early humoral response to COVID-19 vaccination in patients living with obesity and diabetes in France. The COVPOP OBEDIAB study with results from the ANRS0001S COV-POPART cohort

“…Our findings are consistent with an Israeli study on >342 healthcare workers with comorbidities given the BNT162b2 vaccine, which reported that diabetes was significantly associated with lower antibody concentrations (anti-RBD and Nabs) [23] . In contrast, Lee et al reported that T2D patients showed a reduction in CD4+ T-helper-1 (Th1) differentiation following their first dose of BNT162b2 vaccine [24] . However, this initial defect was rectified by the second dose, resulting in levels of CD4+ memory T-cells and CD8+ T cells, anti-RBD IgG, and Nabs that were comparable to healthy individuals at 3–6 months after vaccination [24] .…”

“…In contrast, Lee et al reported that T2D patients showed a reduction in CD4+ T-helper-1 (Th1) differentiation following their first dose of BNT162b2 vaccine [24] . However, this initial defect was rectified by the second dose, resulting in levels of CD4+ memory T-cells and CD8+ T cells, anti-RBD IgG, and Nabs that were comparable to healthy individuals at 3–6 months after vaccination [24] . In one recent Kuwaiti study, both T2D ( n = 81) and non-diabetic individuals ( n = 181) elicited strong immune responses to SARS-CoV-2 BNT162b2 mRNA vaccine; nonetheless, lower levels were seen in people with diabetes, suggesting that continuous monitoring of the antibody levels might be a good indicator to guide personalized needs for further booster shots to maintain adaptive immunity [25] .…”