Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomised controlled trial

ObjectivesSARS‐CoV‐2-induced COVID-19 has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID-19 vaccination.MethodsIn this blinded randomised clinical trial, we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non-seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV-19 (Oxford–AstraZeneca). Patients were stratified according to the presence of peripheral B cells. The primary efficacy endpoint was the difference in the SARS-CoV-2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week 4. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at week 1 and week 4.ResultsSeroconversion rates at week 4 were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccines (p=0.6). Overall, 27% of patients seroconverted; specific T cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. 3/37 (8%) of patients without and 12/18 (67%) of the patients with detectable peripheral B cells seroconverted. No serious adverse events, related to immunisation, were observed.ConclusionsThis enhanced humoral and/or cellular immune response supports an additional booster vaccination in non-seroconverted patients irrespective of a heterologous or homologous vaccination regimen.

Immune response and safety to inactivated COVID-19 vaccine: A comparison between People Living with HIV and HIV-naive individuals

Background: Multi-types COVID-19 vaccines have shown safety and efficacy against COVID-19 in adults. Although current guidelines encourage people living with HIV(PLWH) to take COVID-19 vaccines, whether their immune response to COVID-19 vaccines is distinct from HIV-free individuals is still unclear. Methods: Between March to June 2021, 48 PLWH and 40 HNC, aged 18 to 59 years, were enrolled in the study in Wuchang district of Wuhan city. All of them received inactivated COVID-19 vaccine at day 0 and the second dose at day 28. The primary safety outcome was the combined adverse reactions within 7days after each injection. The primary immunogenicity outcomes were neutralizing antibodies (nAbs) responses by chemiluminescence and total specific IgM and IgG antibodies responses by ELISA and colloidal gold at baseline (day 0), day 14, day 28, day 42, and day 70.Results: In total, the study included 46 PLWH and 38 HNC who finished 70 days’ follow-up. The frequency of adverse reactions to the first and second dose was not different between PLWH (30% and 11%) vs HNC (32% and 24%). There were no serious adverse events. NAbs responses among PLWH peaked at day 70, while among HNC peaked at day 42. At day 42, the geometric mean concentration (GMC) and seroconversion rate of nAbs among PLWH were 4.46 binding antibody units (BAU)/mL (95% CI, 3.18-5.87) and 26% (95% CI, 14-41), which were lower than that among HNC [GMC (18.28 BAU/mL, 95% CI, 10.33-32.33), seroconversion rate (63%, 95% CI, 44-79)]. IgG responses among both PLWH and HNC peaked at day 70. At day 70, the geometric mean ELISA units (GMEU) and seroconversion rate of IgG among PLWH were 0.193 ELISA units (EU)/mL (95% CI, 0.119-0.313) and 51% (95% CI, 34-69), which was lower than that among HNC [GMEU (0.379 BAU/mL, 95% CI, 0.224-0.653), seroconversion rate (86%, 95% CI, 64-97)]. Conclusion: Early humoral immune response to the inactivated COVID-19 vaccine was weaker and delayed among the PLWH population than that among HNC. This observation remained consistent regardless of a high CD4 count and a low HIV viral load suppressed by antiretroviral therapy (ART).

The incidence of COVID-19 infection following emergency use authorization of BBIBP-CORV inactivated vaccine in frontline workers in the United Arab Emirates

Based on the findings from the Phase III clinical trials of inactivated SARS COV-2 Vaccine, (BBIBP-CORV) emergency use authorization (EUA) was granted for the vaccine to frontline workers in the UAE. A prospective cohort study was conducted among frontline workers to estimate the incidence rate and risk of symptomatic COVID-19 infection 14 days after the second dose of inoculation with BBIBP-CORV inactivated vaccine. Those who received two doses of the BBIBP-CORV vaccine in the period from 14th of September 2020 (first dose) to 21st of December 2020 (second dose) were followed up for COVID-19 infections. 11,322 individuals who received the two-dose BBIBP-CORV vaccine were included and were followed up post the second dose plus fourteen days. The incidence rate of symptomatic infection was 0.08 per 1000-person days (95% CI 0.07, 0.10). The estimated absolute risk of developing symptomatic infection was 0.97% (95% CI 0.77%, 1.17%). The confirmed seroconversion rate was 92.8%. There were no serious adverse events reported and no individuals suffered from severe disease. Our findings show that vaccinated individuals are likely to remain protected against symptomatic infection or becoming PCR positive for SARS COV 2 following the second dose of the vaccination.

Healthcare institutions’ recommendation regarding the use of FFP-2 masks and SARS-CoV-2 seropositivity among healthcare workers: a multicenter longitudinal cohort study

Background Health care workers (HCW) are heavily exposed to SARS-CoV-2 from the beginning of the pandemic. We aimed to analyze risk factors for SARS-CoV-2 seroconversion among HCW with a special emphasis on the respective healthcare institutions’ recommendation regarding the use of FFP-2 masks. Methods We recruited HCW from 13 health care institutions (HCI) with different mask policies (type IIR surgical face masks vs. FFP-2 masks) in Southeastern Switzerland (canton of Grisons). Sera of participants were analyzed for the presence of SARS-CoV-2 antibodies 6 months apart, after the first and during the second pandemic wave using an electro-chemiluminescence immunoassay (ECLIA, Roche Diagnostics). We captured risk factors for SARS-CoV-2 infection by using an online questionnaire at both time points. The effects of individual COVID-19 exposure, regional incidence and FFP-2 mask policy on the probability of seroconversion were evaluated with univariable and multivariable logistic regression. Results SARS-CoV-2 antibodies were detected in 99 of 2794 (3.5%) HCW at baseline and in 376 of 2315 (16.2%) participants 6 months later. In multivariable analyses the strongest association for seroconversion was exposure to a household member with known COVID-19 (aOR: 19.82, 95% CI 8.11–48.43, p < 0.001 at baseline and aOR: 8.68, 95% CI 6.13–12.29, p < 0.001 at follow-up). Significant occupational risk factors at baseline included exposure to COVID-19 patients (aOR: 2.79, 95% CI 1.28–6.09, p = 0.010) and to SARS-CoV-2 infected co-workers (aOR: 2.50, 95% CI 1.52–4.12, p < 0.001). At follow up 6 months later, non-occupational exposure to SARS-CoV-2 infected individuals (aOR: 2.54, 95% CI 1.66–3.89 p < 0.001) and the local COVID-19 incidence of the corresponding HCI (aOR: 1.98, 95% CI 1.30–3.02, p = 0.001) were associated with seroconversion. The healthcare institutions’ mask policy (surgical masks during usual exposure vs. general use of FFP-2 masks) did not affect seroconversion rates of HCW during the first and the second pandemic wave. Conclusion Contact with SARS-CoV-2 infected household members was the most important risk factor for seroconversion among HCW. The strongest occupational risk factor was exposure to COVID-19 patients. During this pandemic, with heavy non-occupational exposure to SARS-CoV-2, the mask policy of HCIs did not affect the seroconversion rate of HCWs.

Immunogenicity of Oxford-AstraZeneca COVID-19 Vaccine in Vietnamese Health-Care Workers

We studied the immunogenicity of the Oxford-AstraZeneca vaccine in health-care workers of a major infectious diseases hospital in Vietnam. We measured neutralizing antibodies before and 14 days after each dose, and at day 28 and month 3 after dose 1. A total of 554 workers (136 men and 418 women; age range, 22–71 years; median age, 36 years) participated with the study. Of the 144 participants selected for follow-up after dose 1, 104 and 94 gave blood for antibody measurement at weeks 6 and 8, and at month 3 after dose 1, respectively. The window time between the two doses was 6 weeks. At baseline, none had detectable neutralizing antibodies. After dose 1, the proportion of participants with detectable neutralizing antibodies increased from 27.3% (151 of 554) at day 14 to 78.0% (432 of 554) at day 28. Age correlated negatively with the development and the levels of neutralizing antibodies. However, at day 28, these differences were less profound, and women had a greater seroconversion rate and greater levels of neutralizing antibodies than men. After dose 2, these age and gender associations were not observable. In addition, the proportion of study participants with detectable neutralizing antibodies increased from 70.2% (73 of 104) before dose 2 (week 6, after dose 1) to 98.1% (102 of 104) 14 days later. At month 3, neutralizing antibodies decreased and 94.7% (89 of 94) of the study participants remained seropositive. The Oxford-AstraZeneca COVID-19 vaccine is immunogenic in Vietnamese health-care workers. These data are critical to informing the deployment of the COVID-19 vaccine in Vietnam and in Southeast Asia, where vaccination coverage remains inadequate.

Safety and immunogenicity of anti-SARS CoV-2 conjugate vaccine SOBERANA 02 in a two-dose or three-dose heterologous scheme in adults: Phase IIb Clinical Trial

Background: We report results of immunogenicity, safety and reactogenicity of SOBERANA 02 in a two-dose or three-dose heterologous scheme in adults in a phase IIb clinical trial. Method: This phase IIb trial was designed as parallel, multicentre, adaptive, double blind, randomized and placebo-controlled. Subjects (N=810) aged 19-80 years were randomized to receive two doses of the recombinant SARS CoV-2 receptor binding domain (RBD) conjugated to tetanus toxoid (SOBERANA 02) and a third dose of dimeric RBD (SOBERANA Plus) 28 days apart; two production batches of active ingredient of SOBERANA 02 were evaluated. Primary outcome was the percentage of seroconverted subjects with ≥4-fold the anti-RBD IgG concentration. Secondary outcomes were safety, reactogenicity and neutralizing antibodies. Results: Seroconversion rate in vaccinees was respectively 76.3 and 96.8% after two or three doses, compared with 7.3% in placebo group. Anti-RBD IgG increased significantly after first and second dose of SOBERANA 02 respect to placebo group; and the third dose with SOBERANA Plus boosts the response compared to the second dose. Neutralizing IgG antibodies were detected against D614G and VOCs α, β and δ. Specific and functional antibodies were detected until 7-8 months after the third dose. The frequency of serious adverse events (AEs) associated with vaccination was very low (0.1%); with only one serious AE consistent with vaccination. Local pain was the most frequent AE. Conclusions: Two doses of SOBERANA 02 were well tolerated, safe an immunogenic in adults aged 19-80 years old. The heterologous combination with a third dose of SOBERANA Plus increased neutralizing antibodies, detectable 7-8 months after the third dose. Trial registry: https://rpcec.sld.cu/trials/RPCEC00000347

Adequate Immunogenicity And Low Rate of Severe Adverse Events After SARS-CoV-2 mRNA-Based Vaccination In Patients With Solid Malignancies On Active Treatment Starts To Decline 3 Months After Complete Primary Course of Vaccination

Background: SARS-CoV-2 vaccination in cancer patients is crucial since they are at increased risk of severe COVID-19 disease course, but data on efficacy and safety of vaccination are scarce.Methods: We performed a prospective observational study of patients with solid cancers on active anticancer treatment (chemotherapy, immunotherapy with immune checkpoint inhibitors (ICI) or targeted therapy) that received mRNA-based SARS-CoV-2 vaccination at two institutions in Slovenia. The immunogenicity was assessed by the detection of anti-SARS-CoV-2 S1 IgG antibodies in serum; patients were sampled before, 2-3 weeks after the first dose, 2-3 weeks after the second dose, and 3 months after the complete primary course of vaccination. The results were also compared to controls, sampled at similar time points.Results: Between March and July 2021 112 patients were included in the analysis. The seroconversion rate in patients without prior COVID-19 infection was 96% after the complete primary course of vaccination with 2 doses, compared to 100% for healthy controls. The seroconversion rate after vaccination for patients on chemotherapy, ICI, and targeted therapy was 100%, 91%, and 97%, respectively. All controls and the majority of patients on chemotherapy and targeted therapy, but only 83% for patients on ICI were adequate responders (anti-SARS-CoV-2 S1 IgG ≥ 880 ng/ml). Three months after the vaccination, a significant drop in antibody levels was observed in patients receiving ICI compared to controls (P < 0.001). Adverse events were mostly mild and predictable, none of the patients experienced serious adverse events after vaccination.Conclusions: Immunogenicity after mRNA-based vaccination against SARS-CoV-2 in cancer patients is only slightly impaired, but influenced by the type of anticancer therapy received. Patients on ICI have the slightest and gradual antibody production. Since antibody levels decline after three months, a third vaccination dose is reasonable to provide adequate protection against severe COVID-19 disease course.The study was approved by the National Ethics Committee (No. 0120-39/2021/6)

IMMUNOGENICITY AND SAFETY OF INACTIVATED SARS-COV-2 VACCINE (VERO CELL), BBIBP-CORV (SINOPHARM); AN OBSERVATIONAL STUDY FROM PAKISTAN

Objective: To ascertain the immunogenicity and short-term safety of inactivated SARS-CoV-2 Vaccine (Vero Cell), BBIBPCorV (Sinopharm) in our setup. Study Design: Cross-sectional study. Place and Duration of Study: Combined Military Hospital Sialkot Pakistan, from Feb to Apr 2021. Methodology: A total of 227 health care workers (HCWs) between 18 to 59 years of age were included in the study. Two doses of Inactivated SARS-CoV-2 Vaccine (Vero Cell), BBIBP-CorV were administered to all individuals 21 days apart and they were monitored for any vaccine-related adverse reactions for 7 days after each dose. Neutralizing antibodies (NAbs) in study subjects were detected in three samples i.e. before 1st dose of vaccine, 21 days after 1st dose and 14 days after 2nd dose by Elecsys Anti- SARS-CoV-2 S (Roche Diagnostics). Results: Mean age of individuals in the study was 36.70 ± 18.08 years and most individuals were in the 31-45 years age group. Fatigue and drowsiness were the most common adverse effects experienced by study subjects after 1st and 2nd dose of the vaccine followed by malaise and headache. Only 42 (39%) individuals developed positive neutralizing antibody titers in a sample taken 21 days after 1st dose while all individuals except one (99%) developed positive neutralizing antibody titers in a sample taken 2 weeks after 2nd vaccine dose. Conclusion: Inactivated SARS-CoV-2 Vaccine (Vero Cell), BBIBP-CorV is safe and well-tolerated with very few adverse reactions. Immunogenicity was well achieved as the seroconversion rate was 99% two weeks after 2nd dose of the vaccine.

Seroconversion rate after primary vaccination with two doses of BNT162b2 versus mRNA-1273 in solid organ transplant recipients: a systematic review and meta-analysis

In the general population, the seroconversion rate after primary vaccination with two doses of anti-SARS-CoV-2 mRNA vaccine reaches nearly 100%, with significantly higher antibody titers after mRNA-1273 vaccination compared to BNT162b2 vaccination. Here, we performed a systematic review and meta-analysis to compare the antibody response after two-dose mRNA-1273 versus BNT162b2 vaccination in solid organ transplant (SOT) recipients. A systematic literature research was performed in Pubmed, Web of Science, and the Cochrane library and original research papers were included for a meta-analysis to calculate vaccine-specific seroconversion rates for each of the mRNA vaccines. Next, the pooled relative seroconversion rate was estimated. Six studies that described the development of antibodies against receptor-binding domain (RBD) and/or S1 subunit of the spike protein were eligible for meta-analysis. Two of them also reported antibody titers. The meta-analysis revealed lower seroconversion rates in SOT recipients vaccinated with two doses of BNT162b2 (45.2%; 95% confidence interval (CI) 32.5%-58.3%) than patients vaccinated with two doses of mRNA-1273 (60.4%; 95% CI 47.4%-72.7%. The relative seroconversion rate amounted 0.79 (95% CI 0.71-0.88). This systematic review and meta-analysis indicates that, in SOT recipients, higher seroconversion rates were observed after vaccination with mRNA-1273 compared to BNT162b2.