Humoral Immunogenicity of mRNA Booster Vaccination after Heterologous CoronaVac-ChAdOx1 nCoV-19 or Homologous ChAdOx1 nCoV-19 Vaccination in Patients with Autoimmune Rheumatic Diseases: A Preliminary Report.

Immunogenicity data on the mRNA SARS-CoV-2 vaccine booster after completing a primary series vaccination, other than the mRNA vaccine, in patients with autoimmune rheumatic diseases (ARDs) is scarce. In this study, we reported the humoral immunogenicity of an mRNA booster 90-180 days after completing heterologous CoronaVac/ChAdOx1 nCoV-19 (n = 19) or homologous ChAdOx1 nCoV-19 (n = 14) vaccination by measuring the anti-SARS-CoV-2 receptor binding domain (RBD) IgG levels at one and three months after mRNA booster vaccination. This study included 33 patients with ARDs [78.8% women; mean (SD) age: 42.9 (10.6) years]. Most patients received prednisolone (75.8%, mean [IQR] daily dose: 7.5 [5, 7.5] mg) and azathioprine (45.5%). The seropositivity rates were 100% and 92.9% in CoronaVac/ChAdOx1 and ChAdOx1/ChAdOx1, respectively. The median (IQR) anti-RBD IgG level was lower in the ChAdOx1/ChAdOx1 group than in the CoronaVac/ChAdOx1 group (1867.8 [591.6, 2548.6] vs. 3735.8 [2347.9, 5014.0] BAU/mL, p = 0.061). A similar trend was significant in the third month [597.8 (735.5) vs. 1609.9 (828.4) BAU/mL, p = 0.003]. Minor disease flare-ups occurred in 18.2% of the patients. Our findings demonstrated satisfactory humoral immunogenicity of mRNA vaccine boosters after a primary series, with vaccine strategies other than the mRNA platform. Notably, the vaccine-induced immunity was lower in the ChAdOx1/ChAdOx1 primary series.

Immunogenicity of a fractional or full third dose of AZD1222 vaccine or BNT162b2 messenger RNA vaccine after two doses of CoronaVac vaccines against the Delta and Omicron variants.

OBJECTIVES: The study aimed to compare the immunogenicity and safety of fractional (half) third doses of heterologous COVID-19 vaccines (AZD1222 or BNT162b2) to full doses after the two-dose CoronaVac and when boosting after three different extended intervals. METHODS: At 60-<90, 90-<120, or 120-180 days intervals after the two-dose CoronaVac, participants were randomized to full-dose or half-dose AZD1222 or BNT162b2, followed up at day 28, 60, and 90. Vaccination-induced immune responses to Ancestral, Delta, and Omicron BA.1 strains were evaluated by antispike, pseudovirus, and microneutralization and T cell assays. Descriptive statistics and noninferiority cut-offs were reported as geometric mean concentration or titer and concentration or titer ratios comparing baseline to day 28 and day 90 and different intervals. RESULTS: No safety concerns were detected. All assays and intervals showed noninferior immunogenicity between full doses and half doses. However, full-dose vaccines and/or longer 120-180-day intervals substantially improved the immunogenicity (measured by antispike or measured by pseudotyped virus neutralizing titers 50; P <0.001). Seroconversion rates were over 90% against the SARS-CoV-2 strains by all assays. Immunogenicity waned more quickly with half doses than full doses but remained high against the Ancestral or Delta strains. Against Omicron, the day 28 immunogenicity increased with longer intervals than shorter intervals for full-dose vaccines. CONCLUSION: Immune responses after day 28 when boosting at longer intervals after the two-dose CoronaVac was optimal. Half doses met the noninferiority criteria compared with the full dose by all the immune assays assessed.

Characteristics, Outcomes, and Factors Affecting Mortality in Hospitalized Patients with CAP Due to Different Variants of SARS-CoV-2 and Non-COVID-19 CAP.

The study was conducted from October 2020 to March 2022 in a province in southern Thailand. The inpatients with community-acquired pneumonia (CAP) and more than 18 years old were enrolled. Of the 1511 inpatients with CAP, COVID-19 was the leading cause, accounting for 27%. Among the patients with COVID-19 CAP, mortalities, mechanical ventilators, ICU admissions, ICU stay, and hospital costs were significantly higher than of those with non-COVID-19 CAP. Household and workplace contact with COVID-19, co-morbidities, lymphocytopenia and peripheral infiltration in chest imaging were associated with CAP due to COVID-19. The delta variant yielded the most unfavorable clinical and non-clinical outcomes. While COVID-19 CAP due to B.1.113, Alpha and Omicron variants had relatively similar outcomes. Among those with CAP, COVID-19 infection as well as obesity, a higher Charlson comorbidity index (CCI) and APACHE II score were associated with in-hospital mortality. Among those with COVID-19 CAP, obesity, infection due to the Delta variant, a higher CCI and higher APACHE II score were associated with in-hospital mortality. COVID-19 had a great impact on the epidemiology and outcomes of CAP.

Humoral SARS-CoV-2 immunogenicity wanes 3 months after heterologous inactivated vaccine followed by ChAdOx1 nCoV-19 in autoimmune rheumatic diseases.

BACKGROUND: Alongside vaccine hesitancy, impaired and waning immunity in autoimmune rheumatic diseases (ARDs) are barriers to immunization. The timeframe of immunity waning in ARD remains unclear. OBJECTIVE: We aimed to examine the waning of humoral immunogenicity in a cohort of ARD patients who received the heterologous inactivated vaccine followed by the adenoviral vector SAR-CoV-2 vaccine at a 3-month follow-up. METHODS: The levels of SARS-CoV-2 anti-RBD IgG were evaluated at 1 and 3 months in adults with ARDs (n = 29) and age- and sex-matched healthy controls (HC) that received the heterologous prime-boost CoronaVac vaccine followed by the ChAdOx1 nCoV-19 vaccine. Seropositivity was defined as anti-receptor binding domain (RBD) IgG levels of ≥ 7.15 binding antibody units (BAU)/mL. The kinetic properties of the vaccines were evaluated based on the ratio of anti-RBD IgG values obtained at each follow-up. Disease activity was evaluated. RESULTS: The seropositivity rate was lower among patients with ARDs than among HCs (89.7% vs. 100%, p = 0.237). At 3 months, the median (IQR) anti-RBD IgG level was lower among patients with ARDs than among HCs (122.3 [30.6, 247.8] vs. 294.2 [127.4,605.7] BAU/mL, p = 0.006). Mean antibody levels in patients with ARDs decreased 3.5 (1.9)-fold within 3 months post-vaccination (122.3 [30.6, 247.8] vs. 279.9 [86,1076.5] BAU/mL, p < 0.001). Disease flare-ups occurred in three patients. CONCLUSIONS: Our findings included changes to anti-RBD IgG levels and may inform vaccination strategies. SAR-CoV2 vaccine-induced immunity was lower in patients with ARDs than in HCs and decreased within 3 months, suggesting a need for booster vaccinations.

Impaired neutralizing antibodies and preserved cellular immunogenicity against SARS-CoV-2 in systemic autoimmune rheumatic diseases.

Reports on vaccine immunogenicity in patients with systemic autoimmune rheumatic diseases (SARDs) have been inconclusive. Here, we report the immunogenicity of heterologous prime-boost with an inactivated vaccine followed by an adenoviral vector vaccine in patients with SARDs using anti-RBD antibodies, neutralizing capacity against Omicron BA.2 [plaque-reduction neutralization test (PRNT)], T cell phenotypes, and effector cytokine production at 4 weeks after vaccination. SARD patients had lower median (IQR) anti-RBD-IgG levels and neutralizing function against the Omicron BA.2 variant than the healthy group (p = 0.003, p = 0.004, respectively). T cell analysis revealed higher levels of IFN-γ- and TNF-α-secreting CD4 + T cells (p < 0.001, p = 0.0322, respectively) in SARD patients than in the healthy group. Effector cytokine production by CD8 + T cells was consistent with Th responses. These results suggest that this vaccine regimen revealed mildly impaired humoral response while preserving cellular immunogenicity and may be an alternative for individuals for whom mRNA vaccines are contraindicated.

T-Cell Responses Induced by an Intradermal BNT162b2 mRNA Vaccine Booster Following Primary Vaccination with Inactivated SARS-CoV-2 Vaccine.

A practical booster vaccine is urgently needed to control the coronavirus disease (COVID-19) pandemic. We have previously reported the safety and immunogenicity of a fractional intradermal booster, using the BNT162b2 mRNA vaccine in healthy volunteers who had completed two doses of inactivated SARS-CoV-2 vaccine. In this study, an intramuscular booster at full dosage was used as a control, and a half-dose vaccination was included for reciprocal comparison. Detailed T-cell studies are essential to understand cellular responses to vaccination. T-cell immunity was examined using S1 peptide restimulation and flow cytometry. The fractional dose (1:5) of the BNT162b2 mRNA vaccine enhanced antigen-specific effector T-cells, but the responses were less remarkable compared to the intramuscular booster at full dosage. However, the intradermal regimen was not inferior to the intramuscular booster a month after boosting. An intradermal booster using only one-fifth of the standard dosage could provide comparable T-cell responses with the fractional intramuscular booster. This work confirms the efficacy of intradermal and fractional vaccination in terms of T-cell immunogenicity in previously immunised populations.

Regulatory T Cells Decreased during Recovery from Mild COVID-19.

Depending on the intensity and duration of SARS-CoV-2 infection, the host immune response plays a significant role in immunological protection. Here, we studied the regulatory T-cell (Treg) response in relation to kinetic change and cytokine production in patients with mild COVID-19. Nineteen SARS-CoV-2-positive patients were recruited, and blood was collected at four time points, i.e., seven days after admission, after discharge, and one and three months after recovery. CD3+CD4+CD25+CD127low was marked as the Treg population, with IL-10 and TGF-ß used to study cytokine-producing Tregs. IFN-γ-producing CD8+ T cells were observed for an effector response. The Treg percentage in patients with mild COVID-19 increased during hospitalization compared to during the recovery period. Peripheral blood mononuclear cells (PBMCs) were quantified, and the T-cell response was characterized by re-stimulation with S1 and N peptides. IL-10 and TGF-ß were produced by CD25+CD127low T cells during the active infection phase, especially with N peptide stimulation. Compared to N peptide stimulation, S1 peptide stimulation provided superior IFN-γ-secreting CD8+ T-cell responses. Our results suggest that while IFN-γ+CD8+ T cells confer antiviral immunity, cytokine-producing Tregs may have a substantial role in regulating inflammatory responses in mild SARS-CoV-2 infection. Novel vaccine development may also consider enhancing T-cell repertoires.

Coronavirus Disease 2019 Vaccinations in Patients With Chronic Liver Disease and Liver Transplant Recipients: An Update.

Coronavirus disease 2019 (COVID-19) is a current global pandemic associated with an increased mortality, particularly in patients with comorbidities. Patients with chronic liver disease (CLD) and liver transplant (LT) recipients are at higher risk of morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Many liver societies have recommended that these patients should receive COVID-19 vaccinations, although there are limited studies assessing risks and benefits in this population. In addition, two doses of mRNA vaccines may not provide sufficient immune response, and booster dose(s) may be necessary, especially in LT recipients. Notably, variants of concern have recently emerged, and it remains unclear whether currently available vaccines provide adequate and durable protective immunity against these novel variants. This review focuses on the role of COVID-19 vaccinations in CLD and LT recipients.

Immunogenicity and Safety of an Intradermal BNT162b2 mRNA Vaccine Booster after Two Doses of Inactivated SARS-CoV-2 Vaccine in Healthy Population.

Effective vaccine coverage is urgently needed to tackle the COVID-19 pandemic. Inactivated vaccines have been introduced in many countries for emergency usage, but have only provided limited protection. Heterologous vaccination is a promising strategy to maximise vaccine immunogenicity. Here, we conducted a phase I, randomised control trial to observe the safety and immunogenicity after an intradermal boost, using a fractional dosage (1:5) of BNT162b2 mRNA vaccine in healthy participants in Songkhla, Thailand. In total, 91 volunteers who had been administered with two doses of inactivated SARS-CoV-2 (CoronaVac) were recruited into the study, and then randomised (1:1:1) to received different regimens of the third dose. An intramuscular booster with a full dose of BNT162b2 was included as a conventional control, and a half dose group was included as reciprocal comparator. Both, immediate and delayed adverse events following immunisation (AEFI) were monitored. Humoral and cellular immune responses were examined to observe the booster effects. The intradermal booster provided significantly fewer systemic side effects, from 70% down to 19.4% (p < 0.001); however, they were comparable to local reactions with the conventional intramuscular booster. In the intradermal group after receiving only one fifth of the conventional dosage, serum Anti-RBD IgG was halved compared to the full dose of an intramuscular injection. However, the neutralising function against the Delta strain remained intact. T cell responses were also less effective in the intradermal group compared to the intramuscular booster. Together, the intradermal booster, using a fractional dose of BNT162b2, can reduce systemic reactions and provides a good level and function of antibody responses compared to the conventional booster. This favourable intradermal boosting strategy provides a suitable alternative for vaccines and effective vaccine management to increase the coverage during the vaccine shortage.

Using an effective TB vaccination regimen to identify immune responses associated with protection in the murine model.

A vaccine against tuberculosis (TB), a disease resulting from infection with Mycobacterium tuberculosis (M.tb), is urgently needed to prevent more than a million deaths per year. Bacillus Calmette-Guérin (BCG) is the only available vaccine against TB but its efficacy varies throughout the world. Subunit vaccine candidates, based on recombinant viral vectors expressing mycobacterial antigens, are one of the strategies being developed to boost BCG-primed host immune responses and efficacy. A promising vaccination regimen composed of intradermal (i.d.) BCG prime, followed by intranasally (i.n.) administered chimpanzee adenoviral vector (ChAdOx1) and i.n. or i.d. modified vaccinia Ankara virus (MVA), both expressing Ag85A, has been previously reported to significantly improve BCG efficacy in mice. Effector and memory immune responses induced by BCG-ChAdOx1.85A-MVA85A (B-C-M), were evaluated to identify immune correlates of protection in mice. This protective regime induced strong Ag85A-specific cytokine responses in CD4+ and CD8+ T cells, both in the systemic and pulmonary compartments. Lung parenchymal CXCR3+ KLRG1- Ag85A-specific memory CD4+ T cells were significantly increased in B-C-M compared to BCG immunised mice at 4, 8 and 20 weeks post vaccination, but the number of these cells decreased at the latter time point. This cell population was associated with the protective efficacy of this regime and may have an important protective role against M.tb infection.