Dataset Information

Immunogenicity, efficacy, and safety of SARS-CoV-2 vaccine dose fractionation: a systematic review and meta-analysis.

ABSTRACT:

Background

Dose fractionation of a coronavirus disease 2019 (COVID-19) vaccine could effectively accelerate global vaccine coverage, while supporting evidence of efficacy, immunogenicity, and safety are unavailable, especially with emerging variants.

Methods

We systematically reviewed clinical trials that reported dose-finding results and estimated the dose-response relationship of neutralizing antibodies (nAbs) of COVID-19 vaccines using a generalized additive model. We predicted the vaccine efficacy against both ancestral and variants, using previously reported correlates of protection and cross-reactivity. We also reviewed and compared seroconversion to nAbs, T cell responses, and safety profiles between fractional and standard dose groups.

Results

We found that dose fractionation of mRNA and protein subunit vaccines could induce SARS-CoV-2-specific nAbs and T cells that confer a reasonable level of protection (i.e., vaccine efficacy > 50%) against ancestral strains and variants up to Omicron. Safety profiles of fractional doses were non-inferior to the standard dose.

Conclusions

Dose fractionation of mRNA and protein subunit vaccines may be safe and effective, which would also vary depending on the characteristics of emerging variants and updated vaccine formulations.

SUBMITTER: Yang B

PROVIDER: S-EPMC9595080 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Immunogenicity, efficacy, and safety of SARS-CoV-2 vaccine dose fractionation: a systematic review and meta-analysis.

Yang Bingyi B Huang Xiaotong X Gao Huizhi H Leung Nancy H NH Tsang Tim K TK Cowling Benjamin J BJ

BMC medicine 20221025 1

<h4>Background</h4>Dose fractionation of a coronavirus disease 2019 (COVID-19) vaccine could effectively accelerate global vaccine coverage, while supporting evidence of efficacy, immunogenicity, and safety are unavailable, especially with emerging variants.<h4>Methods</h4>We systematically reviewed clinical trials that reported dose-finding results and estimated the dose-response relationship of neutralizing antibodies (nAbs) of COVID-19 vaccines using a generalized additive model. We predicted ...[more]

PMID: 36284331

Similar Datasets

Project description:Rationale and objectiveCOVID-19 vaccination is the most effective way to prevent COVID-19. For chronic kidney disease patients on long-term dialysis, there is a lack of evidence on the pros and cons of COVID-19 vaccination. This study was conducted to investigate the immunogenicity and safety of COVID-19 vaccines in patients on dialysis.MethodsPubMed, MEDLINE, EMBASE, and the Cochrane Library were systemically searched for cohort, randomized controlled trials (RCTs), and cross-sectional studies. Data on immunogenicity rate, antibody titer, survival rate, new infection rate, adverse events, type of vaccine, and patient characteristics such as age, sex, dialysis vintage, immunosuppression rate, and prevalence of diabetes were extracted and analyzed using REVMAN 5.4 and Stata software. A random effects meta-analysis was used to perform the study.ResultsWe screened 191 records and included 38 studies regarding 5,628 participants. The overall immunogenicity of dialysis patients was 87% (95% CI, 84-89%). The vaccine response rate was 85.1 in hemodialysis patients (HDPs) (1,201 of 1,412) and 97.4% in healthy controls (862 of 885). The serological positivity rate was 82.9% (777 of 937) in infection-naive individuals and 98.4% (570 of 579) in patients with previous infection. The Standard Mean Difference (SMD) of antibody titers in dialysis patients with or without previous COVID-19 infection was 1.14 (95% CI, 0.68-1.61). Subgroup analysis showed that the immunosuppression rate was an influential factor affecting the immunogenicity rate (P < 0.0001). Nine studies reported safety indices, among which four local adverse events and seven system adverse events were documented.ConclusionsVaccination helped dialysis patients achieve effective humoral immunity, with an overall immune efficiency of 87.5%. Dialysis patients may experience various adverse events after vaccination; however, the incidence of malignant events is very low, and no reports of death or acute renal failure after vaccination are available, indicating that vaccine regimens may be necessary.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42022342565, identifier: CRD42022342565.

Project description:BackgroundThis review summarizes the factors influencing the efficacy and safety of the COVID-19 vaccine in LTR through meta-analysis, hoping to provide strategies for vaccine use.MethodsElectronic databases were screened for studies on mRNA vaccines in LTR. The primary outcome was the pooled seroconversion rate, and the secondary outcome was the incidence of adverse events+breakthrough infections. Subgroup analyses were made based on BMI, associated comorbidities, presence of baseline leukopenia, time since transplant, and drugs used.ResultIn total, 31 articles got included. The pooled seroconversion rate after at least two doses of SARS-CoV-2 vaccination was 72% (95% CI [0.52-0.91). With significant heterogeneity among studies I2 = 99.9%, the seroconversion rate was about 72% (95%CI [0.66-0.75]), from the studies reporting two doses of vaccine slightly higher around 75%(95%CI [0.29-1.22]) from studies reporting three doses. The pooled seroconversion rate within the lower to normal BMI group was 74% (95% CI [0.22-1.27], Pi=0.005) against 67% (95% CI [0.52-0.81], Pi=0.000) in the high BMI group. The pooled seroconversion rate in the ''positive leukopenia'' group was the lowest, 59%. Leukopenia could influence the vaccine seroconversion rate in LTR. From the time since transplant analysis after setting seven years as cut off point, the pooled seroconversion rate after at least two doses of COVID-19 vaccination was 53% (95% CI [0.18-0.83], P=0.003, I2 = 99.6%) in <7years group and 83% (95% CI [0.76-0.90], P=0.000 I2 = 95.7%) in > 7years group. The only time since transplantation had reached statistical significance to be considered a risk factor predictor of poor serological response (OR=1.27 95%CI [1.03-1.55], P=0.024). The breakthrough infection rate after vaccination was very low2% (95% CI 0.01-0.03, I2 = 63.0%), and the overall incidence of adverse events, which included mainly pain at the injection site and fatigue, was 18% (95%CI [0.11-0.25], I2 = 98.6%, Pi=0.000).ConclusionThe seroconversion rate in LTR vaccinated with at least two doses of mRNA COVID-19 vaccine could be significantly affected by the vaccine type, immunosuppressant used, BMI, leukopenia, associated comorbidities, and time since transplantation. Nevertheless, booster doses are still recommended for LTR.

Project description:In allogeneic stem cell transplant (Allo-SCT) recipients, the cell-mediated and humoral immunogenicity of the 3-dose SARS-CoV-2 vaccination schedule has not been investigated in prospective studies. In a prospective cohort, we recruited 122 Allo-SCT recipients since August 2021, when Ontario began offering a 3-dose vaccine schedule for Allo-SCT recipients. We determined humoral and cell-mediated immunity and adverse effects of the 3-dose SARS-COV-2 vaccination schedule in Allo-SCT recipients. In immunogenicity analysis (n = 95), the median (interquartile range [IQR]) antibody titer against the receptor-binding domain (RBD) of the spike (S) protein after the third dose (10,358.0 U/mL [IQR = 673.9-31,753.0]) was significantly higher than that after the first (10.2 U/mL [IQR = 0.6-37.0]) and the second doses (125.6 U/mL [IQR = 2.8-1251.0]) (P < .0001). The haploidentical donor status was an independent risk factor (adjusted odds ratio = 7.67, 95% confidence interval [CI], 1.86-31.60) for suboptimal antibody response (anti-RBD < 100 U/mL). S-specific CD4+ and CD8+ T-cell responses were measured in a subset of Allo-SCT recipients (n = 20) by flow cytometry. Most developed antigen-specific CD4+ (55%-80%) and CD8+ T-cells (80%) after 2 doses of vaccine. Frequencies of CD4+ polyfunctional (P = .020) and IL-2 monofunctional (P = .013) T-cells significantly increased after the third dose. Twenty-three episodes (23/301 doses [7.6%]) of new-onset or worsening pre-existing graft-versus-host disease (GVHD) occurred, including 4 episodes after the third dose. We observed 4 relapses (3.27%). Seven patients developed SARS-CoV-2 infection despite vaccination, although none required hospitalization. In conclusion, the 3-dose SARS-CoV-2 vaccine schedule provided immunity associated with a low risk of GVHD and other adverse effects. This prospective cohort showed that the third dose of SARS-CoV-2 vaccine in allogeneic stem cell transplant recipients promoted better humoral and cellar immune responses than after the initial series without increasing the risk of GVHD or severe adverse effects.

Dataset Information

Immunogenicity, efficacy, and safety of SARS-CoV-2 vaccine dose fractionation: a systematic review and meta-analysis.

Background

Methods

Results

Conclusions

Publications

Immunogenicity, efficacy, and safety of SARS-CoV-2 vaccine dose fractionation: a systematic review and meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets