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.

Analysis of neutralizing antibodies to COVID-19 inactivated or subunit recombinant vaccines in hospitalized patients with liver dysfunction.

Background: The neutralizing antibodies (NAbs) response after COVID-19 vaccination after liver dysfunction is unclear. In this study, we evaluated the NAbs response after COVID-19 vaccination in hospitalized patients suffering from liver dysfunction. Methods: In this cross-sectional study with longitudinal follow-up, we enrolled eligible patients with liver dysfunction and healthy volunteers with full-course COVID-19 vaccination. Blood samples were collected for the NAbs testing at the time of admission and after treatment. Multiple regression analysis to assess independent risk factors affecting NAbs response. Results: A total of 137 patients and 134 healthy controls (HC) were enrolled. Both seropositivity (65.7% vs 80.6%, p<0.01) and titer (3.95 vs 4.94 log2 AU/ml, p<0.001) of NAbs in patients were significantly lower than that in HC. The decrease of antibody titer in patients was significantly faster than that in HC. After adjusting for potential confounding factors, males (odds ratio [OR]: 0.17; 95% confidence interval [CI]: 0.06, 0.46; p<0.001) and severe liver damage (OR: 0.30; 95% CI: 0.12, 0.71; p<0.01) were significantly associated with reduction of the probability of NAbs seropositivity in the multiple regression analysis. Males (ß =-1.18; 95% CI: -1.73,-0.64) and chronic liver diseases (ß =-1.45; 95% CI: -2.13, -0.76) were significantly associated with lower NAbs titers. In 26 patients with liver failure, both antibody seropositivity (53.8% vs 84.6%, p<0.05) and titer (3.55 vs 4.32 log2 AU/ml, p<0.001) did not decrease but increased after artificial liver plasmapheresis. Conclusions: NAbs response to COVID-19 inactivated or subunit recombinant vaccines was waning in patients with liver dysfunction. Moreover, patients with male sex, severe liver injury and chronic liver diseases have an increased risk of poor antibody responses.

Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2.

Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, most current mRNA delivery platforms need to be stored at -20 °C or -70 °C due to their poor stability, which severely restricts their availability. Herein, we develop a lyophilization technique to prepare SARS-CoV-2 mRNA-lipid nanoparticle vaccines with long-term thermostability. The physiochemical properties and bioactivities of lyophilized vaccines showed no change at 25 °C over 6 months, and the lyophilized SARS-CoV-2 mRNA vaccines could elicit potent humoral and cellular immunity whether in mice, rabbits, or rhesus macaques. Furthermore, in the human trial, administration of lyophilized Omicron mRNA vaccine as a booster shot also engendered strong immunity without severe adverse events, where the titers of neutralizing antibodies against Omicron BA.1/BA.2/BA.4 were increased by at least 253-fold after a booster shot following two doses of the commercial inactivated vaccine, CoronaVac. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity and significantly improves their accessibility, particularly in remote regions.

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.