Weakened humoral and cellular immune response to the inactivated COVID-19 vaccines in Chinese individuals with obesity/overweight.

Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population. However, limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines. In this study, 132 high BMI (Body mass index) (obesity and overweight, BMI ≥ 24 kg/m2) and 82 normal BMI (BMI < 24 kg/m2) participants were enrolled. Adverse events (AEs), Spike receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibodies (NAbs), and specific B-cell and T-cell responses were evaluated 21-105 days after full-course inactivated COVID-19 vaccination. The overall incidence of adverse events (AEs) was similar in individuals with and without obesity/overweight. No serious vaccine-related AEs occurred. Individuals with obesity/overweight had a reduced seropositivity rate of NAbs compared to those with normal BMI. Anti-RBD-IgG and NAbs titers in the high BMI group were significantly lower than those in the normal BMI group. The frequencies of RBD-specific memory B cells (MBCs) and the numbers of spike-specific TNF-α+ spot-forming cells (SFCs) in individuals with obesity/overweight were reduced compared with those noted in individuals without obesity/overweight. A similar trend of weakened humoral responses was also observed in individuals with central obesity. Our study results suggested that inactivated COVID-19 vaccines were safe and well tolerated but induced poor humoral and cellular immune responses in Chinese individuals with obesity/overweight.

Dynamic immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in people living with HIV: A longitudinal observational study.

People living with HIV (PLWH) have poor outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); vaccination reduces the associated mortality. The humoral immune response dynamics after booster inactivated vaccinations in PLWH remain unclear. In this longitudinal observational study, 100 PLWH after primary inactivated SARS-CoV-2 vaccination were consecutively recruited and followed up. After booster vaccination (BV), neutralizing antibodies (NAbs) were detected at 1 month from all the PLWH, and the titer increased sixfold compared to that associated with the primary vaccination (PV), similar to that in healthy controls after BV. The NAbs titer declined over time after BV, but remained higher at 6 months than after PV. The NAbs response was elevated after BV with CD4 count <200 cells/µL, it was the poorest among the different CD4 cell count subgroups. Similar results were observed for anti-RBD-IgG responses. Moreover, RBD-specific MBCs were significantly elevated after BV in PLWH. No serious AEs were observed after BV in PLWH. In conclusion, booster inactivated SARS-CoV-2 vaccination is well tolerated and can elicit robust and durable humoral responses in PLWH. PLWH may benefit from a third dose of the inactivated vaccine.

Humoral responses after primary and booster SARS-CoV-2 inactivated vaccination in patients with chronic hepatitis B virus infection: A longitudinal observational study.

Given the pandemic of severe acute respiratory syndrome coronavirus 2 Omicron variants, booster vaccination (BV) using inactivated virus vaccines (the third dose) has been implemented in China. However, the immune responses after BV, especially those against Omicron, in patients with chronic hepatitis B virus (HBV) infection (CHB) are unclear. In this prospective longitudinal study, 114 patients with CHB and 68 healthy controls (HCs) were recruited after receiving inactivated vaccination. The anti-receptor-binding domain (RBD) immunoglobulin G (IgG), neutralizing antibodies (NAbs), neutralization against Omicron (BA2.12.1, BA.4/5), and specific B/T cells were evaluated. In patients, anti-RBD IgG was elevated significantly after BV; the titers were as high as those in HCs. Similar results were obtained for the NAbs. However, compared with that against wild type (WT), the neutralization against Omicron was compromised after BV. The frequency of RBD+ atypical memory B cells increased, but spike-specific cluster of differentiation 4+ /8+ T cells remained unchanged after BV. Moreover, no serious adverse events or HBV reactivation were observed after BV. These results suggest that BV significantly enhanced antibody responses against WT; however, it resulted in compromised antibody responses against Omicron in patients with CHB. Hence, new all-in-one vaccines and optimal vaccination strategies should be studied promptly.

Decreased antibody response to influenza vaccine with an enhanced antibody response to subsequent SARS-CoV-2 vaccination in patients with chronic hepatitis B virus infection.

INTRODUCTION: Influenza or SARS-CoV-2 vaccination is especially recommended for people with underlying diseases. For the large number of patients with chronic hepatitis B virus infection (CHB), studies on their immune responses to these vaccines are still lacking. METHODS: A total of 57 CHB patients and 19 healthy controls (HCs) receiving inactivated influenza vaccination were prospectively followed up. Influenza-specific immunoglobulin G (IgG) antibodies (anti-H1N1, anti-H3N2, and anti-B IgG), antibody-secreting cells (ASCs), and circulating T follicular helper cells were assessed simultaneously. Eight CHB patients subsequently got inactivated SARS-CoV-2 vaccination during 1-year follow-up, and levels of serum antibodies against SARS-CoV-2 were further analyzed. RESULTS: On day 28 after influenza vaccination, three influenza antibodies levels appeared to be lower in CHB patients than in HCs. And anti-H1N1 IgG level was significantly decreased in cirrhotic patients (p < .05). Anti-H1N1 IgG levels (day 28) were positively correlated with ASC frequencies (day 7) (p < .05), and negatively correlated with cirrhosis and hepatitis B surface antigen levels (p < .05). Anti-SARS-CoV-2 antibodies were higher in patients with influenza vaccination history than in patients without the history (p < .05). Moreover, positive correlations existed between influenza vaccination history and anti-SARS-CoV-2 antibody levels (p < .01). CONCLUSIONS: CHB patients, especially those with cirrhosis, appeared to have a decreased antibody response to inactivated influenza vaccine. A history of inactivated influenza vaccination within 1 year before inactivated SARS-CoV-2 vaccination might induce stronger anti-SARS-CoV-2 antibody response.

Decreased antibody response to influenza vaccine with an enhanced antibody response to subsequent SARS‐CoV‐2 vaccination in patients with chronic hepatitis B virus infection

Introduction Influenza or SARS‐CoV‐2 vaccination is especially recommended for people with underlying diseases. For the large number of patients with chronic hepatitis B virus infection (CHB), studies on their immune responses to these vaccines are still lacking. Methods A total of 57 CHB patients and 19 healthy controls (HCs) receiving inactivated influenza vaccination were prospectively followed up. Influenza‐specific immunoglobulin G (IgG) antibodies (anti‐H1N1, anti‐H3N2, and anti‐B IgG), antibody‐secreting cells (ASCs), and circulating T follicular helper cells were assessed simultaneously. Eight CHB patients subsequently got inactivated SARS‐CoV‐2 vaccination during 1‐year follow‐up, and levels of serum antibodies against SARS‐CoV‐2 were further analyzed. Results On day 28 after influenza vaccination, three influenza antibodies levels appeared to be lower in CHB patients than in HCs. And anti‐H1N1 IgG level was significantly decreased in cirrhotic patients (p < .05). Anti‐H1N1 IgG levels (day 28) were positively correlated with ASC frequencies (day 7) (p < .05), and negatively correlated with cirrhosis and hepatitis B surface antigen levels (p < .05). Anti‐SARS‐CoV‐2 antibodies were higher in patients with influenza vaccination history than in patients without the history (p < .05). Moreover, positive correlations existed between influenza vaccination history and anti‐SARS‐CoV‐2 antibody levels (p < .01). Conclusions CHB patients, especially those with cirrhosis, appeared to have a decreased antibody response to inactivated influenza vaccine. A history of inactivated influenza vaccination within 1 year before inactivated SARS‐CoV‐2 vaccination might induce stronger anti‐SARS‐CoV‐2 antibody response. Antibody response to an inactivated influenza vaccine appears to be reduced in patients with CHB, especially in those with cirrhosis. A history of inactivated influenza vaccination within 1 year before inactivated SARS‐CoV‐2 vaccination might result in a stronger anti‐SARS‐CoV‐2 antibody response

Risk of waning humoral responses after inactivated or subunit recombinant SARS-CoV-2 vaccination in patients with chronic diseases: Findings from a prospective observational study in China.

Heterogeneity of antibody responses has been reported in SARS-CoV-2 vaccination recipients with underlying diseases. We investigated the impact of the presence of comorbidities on the humoral response to SARS-CoV-2 vaccination in patients with chronic disease (PWCD) and assessed the effect of the number of comorbidities on the humoral response to vaccination. In this study, neutralizing antibodies (NAbs) and IgG antibodies against the receptor-binding domain (RBD-IgG) were monitored following a full-course vaccination. In total, 1400 PWCD (82.7%, inactivated vaccines; 17.3%, subunit recombinant vaccine) and 245 healthy controls (65.7% inactivated vaccines, 34.3% subunit recombinant vaccine) vaccinated with inactivated or subunit recombinant SARS-CoV-2 vaccines, were included. The seroconversion and antibody levels of the NAbs and RBD-IgG were different in the PWCD group compared with those in the control group. Chronic hepatitis B (odds ratio [OR]: 0.65; 95% confidence interval [CI]: 0.46-0.93), cancer (OR: 0.65; 95% CI: 0.42-0.99), and diabetes (OR: 0.50; 95% CI: 0.28-0.89) were associated with lower seroconversion of NAbs. Chronic kidney disease (OR: 0.29; 95% CI: 0.11-0.76), cancer (OR: 0.38; 95% CI: 0.23-0.62), and diabetes (OR: 0.37; 95% CI: 0.20-0.69) were associated with lower seroconversion of RBD-IgG. Only the presence of autoimmune disease showed significantly lower NAbs and RBD-IgG titers. Patients with most types of chronic diseases showed similar responses to the controls, but humoral responses were still significantly associated with the presence of ≥2 coexisting diseases. Our study suggested that humoral responses following SARS-CoV-2 vaccination are impaired in patients with certain chronic diseases.

Association between immunosuppressants and poor antibody responses to SARS-CoV-2 vaccines in patients with autoimmune liver diseases.

The antibody and B cell responses after inactivated SARS-CoV-2 vaccination have not been well documented in patients with autoimmune liver disease (AILD). Therefore, we conducted a prospective observational study that included AILD patients and healthy participants as controls between July 1, 2021, and September 30, 2021, at the Second Affiliated Hospital of Chongqing Medical University. All adverse events (AEs) after the COVID-19 vaccination were recorded and graded. Immunoglobulin (Ig)-G antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (anti-RBD-IgG) and neutralizicadng antibodies (NAbs) were tested following full-course vaccination (BBIBP-CorV or CoronaVac). In addition, SARS-CoV-2-specific B cells were detected by flow cytometry. In total, 76 AILD patients and 136 healthy controls (HCs) were included. All AEs were mild and self-limiting, and the incidences were similar between the AILD and HCs. The seropositivity rates of anti-RBD-IgG and NAbs in AILD were 97.4% (100% in HCs, p = 0.13) and 63.2% (84.6% in HCs, p < 0.001), respectively. The titers of anti-RBD-IgG and NAbs were significantly lower in AILD patients than those in HCs. After adjusting for confounders, immunosuppressive therapy was an independent risk factor for low-level anti-RBD-IgG (adjusted odds ratio [aOR]: 4.7; 95% confidence interval [CI], 1.5-15.2; p = 0.01) and a reduced probability of NAbs seropositivity (aOR, 3.0; 95% CI, 1.0-8.9; p = 0.04) in AILD patients. However, regardless of immunosuppressants, the SARS-CoV-2-specific memory B cells responses were comparable between the AILD and HC groups. Our results suggest that inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) are safe, but their immunogenicity is compromised in patients with AILD. Moreover, immunosuppressants are significantly associated with poor antibody responses to the SARS-CoV-2 vaccines. These results could inform physicians and policymakers about decisions on screening the populations at higher risk of poor antibody responses to SARS-CoV-2 vaccines and providing additional vaccinations in patients with AILD.

Safety and immunogenicity of inactivated SARS-CoV-2 vaccines in people living with HIV.

It is important to know the safety and efficacy of vaccination in immunocompromised people living with HIV (PLWH), but currently, there is limited data on the inactivated SARS-CoV-2 vaccines' safety and immune responses in PLWH. In this prospective observational study, 139 PLWH and 120 healthy controls were enrolled and monitored for 21-105 days after a two-dose vaccination. The safety, anti-receptor binding domain IgG (anti-RBD-IgG) and anti-spike-IgG responses, and RBD-specific memory B cell (MBC) responses were evaluated. The overall adverse events within seven days were reported in 12.9% (18/139) of PLWH and 13.3% (16/120) of healthy controls. No serious adverse events occurred in both groups. Overall, the seroprevalence of anti-RBD-IgG in PLWH was significantly decreased (87.1% vs. 99.2%; p<0.001). The geometric mean end-point titer (GMT) of anti-RBD-IgG in PLWH was also reduced, especially in patients with CD4 counts <200 cells/µL, regardless of age, gender, or HIV viral load. GMTs of anti-RBD-IgG in both PLWH and healthy controls declined gradually over time. Similar results were also observed in the anti-spike-IgG response. The frequency of RBD-specific MBCs in PLWH decreased (p<0.05), and then remained stable over time. Lastly, through multivariate analysis, we found the factors that predicted a less robust response to inactivated vaccines in PLWH were a low CD4 count and long time interval after vaccination. In conclusion, inactivated vaccines are well-tolerated in PLWH but with low immunogenicity. Therefore, SARS-CoV-2 vaccines and booster doses should be given priority in PLWH, especially in patients with low CD4 counts.Trial registration: ClinicalTrials.gov identifier: NCT05043129..

Safety and antibody response to inactivated COVID-19 vaccine in patients with chronic hepatitis B virus infection.

BACKGROUND AND AIMS: The safety and antibody responses of coronavirus disease 2019 (COVID-19) vaccination in patients with chronic hepatitis B (CHB) virus infection is still unclear, and exploration in safety and antibody responses of COVID-19 vaccination in CHB patients is significant in clinical practice. METHODS: 362 adult CHB patients and 87 healthy controls at an interval of at least 21 days after a full-course vaccination (21-105 days) were enrolled. Adverse events (AEs) were collected by questionnaire. The antibody profiles at 1, 2 and 3 months were elucidated by determination of anti-spike IgG, anti-receptor-binding domain (RBD) IgG, and RBD-angiotensin-converting enzyme 2 blocking antibody. SARS-CoV-2 specific B cells were also analysed. RESULTS: All AEs were mild and self-limiting, and the incidence was similar between CHB patients and controls. Seropositivity rates of three antibodies were similar between CHB patients and healthy controls at 1, 2 and 3 months, but CHB patients had lower titers of three antibodies at 1 month. Compared to healthy controls, HBeAg-positive CHB patients had higher titers of three antibodies at 3 months (all P < .05) and a slower decline in antibody titers. Frequency of RBD-specific B cells was positively correlated with titers of anti-RBD IgG (OR = 1.067, P = .004), while liver cirrhosis, antiviral treatment, levels of HBV DNA, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and total bilirubin (TB) were not correlated with titers of anti-RBD IgG. CONCLUSIONS: Inactivated COVID-19 vaccines were well tolerated, and induced effective antibody response against SARS-CoV-2 in CHB patients.