In a recent study published in Microbe, researchers performed a meta-analysis analyzing randomized controlled trials (RCTs) that evaluated the effectiveness of coronavirus disease 2019 (COVID-19) vaccines and the dose-response association of humoral responses with vaccine effectiveness.

Study: Efficacy of SARS-CoV-2 vaccines and the dose–response relationship with three major antibodies: a scientific review and meta-analysis of randomised controlled trials. Image Credit: Corona Borealis Studio/Shutterstock

Background

COVID-19 has caused unprecedented morbidity and mortality across the globe. COVID-19 vaccine effectiveness in averting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection severity outcomes, including deaths, shouldn’t be certain due to the limited availability of information from individual clinical trials. Longitudinal data on vaccine effectiveness changes with time are also limited.

Anti-SARS-CoV-2 antibody titers are used for estimating the effectiveness of novel vaccines, heterologous and homologous vaccination regimens, and booster vaccinations, the effectiveness trial data for that are limited. Humoral response-based estimates could be valid in case of dose-response associations between antibody titers and vaccine effectiveness. Nevertheless, such associations usually are not well-characterized.

Concerning the study

In the current study, researchers assessed the effectiveness of COVID-19 vaccines in averting COVID-19 and evaluated the dosage-response relationships between humoral responses and COVID-19 vaccine effectiveness.

Databases equivalent to Embase, PubMed, Web of Science, Scopus, Cochrane Library, World Health Organization (WHO) COVID-19 research database, and the medRxiv and bioRxiv preprint servers, were looked for RCTs on the clinical effectiveness of COVID-19 vaccines, published between 1 January 2020 and 12 September 2022. Polymerase chain response (PCR)-confirmed outcomes were evaluated. Data were searched with none language restrictions. Bias risks within the included RCTs were evaluated using the Cochrane risk of the bias assessment tool, and the standard of evidence was determined using the grading of recommendations assessment, development and evaluation (GRADE) framework.

Probable heterogeneity sources were investigated. Frequentist-type random-effects modeling was performed to judge vaccine effectiveness for the common outcomes of asymptomatic and symptomatic SARS-CoV-2 infections. Bayesian-type random-effects modeling was performed for the severity outcomes, including severe infections, hospitalizations and death.

Meta-regression modeling was performed to evaluate the dosage-response associations of neutralizing, anti-SARS-CoV-2 spike (S) protein immunoglobulin G (IgG), and anti-S receptor-binding domain (RBD) IgG titers with vaccine effectiveness in averting symptomatic and severe SARS-CoV-2 infections. Two groups of researchers performed literature screening independently, and disagreements were resolved by one other group of researchers.

Studies lacking COVID-19 vaccine effectiveness data, including conference abstracts and duplicate records, were excluded from the evaluation. For studies with similar sample populations, records with the longest duration of follow-up were included. Within the case vaccine effectiveness and humoral responses weren’t documented in the identical paper, corresponding prior trials on vaccine immunogenicity (at similar doses) were identified.

Results

Out of 41,053 records, 28 RCTs, in 32.0 publications, comprising 286,915 and 233,236 individuals within the vaccinated and placebo groups, respectively, with one to 6 months of follow-up (median), following essentially the most recent vaccination, were considered for the evaluation. The effectiveness of two-dose deoxyribonucleic acid (DNA), messenger ribonucleic acid (mRNA), inactivated, recombinant protein, and viral vector COVID-19 vaccines was evaluated in 27 clinical trials.

Booster vaccinations were in comparison with no COVID-19 vaccinations in two trials. The combined efficacies of two-dose prime vaccination in averting asymptomatic SARS-CoV-2 infections, symptomatic SARS-CoV-2 infections, hospitalizations, severe COVID-19, and deaths were 45%, 77%, 95%, 91%, and 86%, respectively.

Vaccine effectiveness was heterogeneous against symptomatic and asymptomatic infections however the evidence was inadequate to find out whether the differences in effectiveness could result from vaccine type, vaccinee age, and the dosing intervals. Vaccine effectiveness against SARS-CoV-2 symptomatic infections waned with time following two-dose vaccinations, with a 14% (mean) reduction monthly, which might be increased by booster doses.  

A statistically significant but non-linear association was observed between the antibody type and vaccine effectiveness against severe and symptomatic SARS-CoV-2 infections. Bias risks were found to be low in many of the included RCTs. Sensitivity analyses yielded similar findings because the predominant evaluation, indicating the robustness of the outcomes.

Conclusions

Overall, the study findings provided moderate-quality evidence showing that COVID-19 vaccine effectiveness was high for severe SARS-CoV-2 infections and deaths and modest for stopping mild COVID-19. Two-dose vaccine-induced immunity waned with time but might be elevated by booster vaccinations. Greater antibody titers were related to greater vaccine effectiveness; nevertheless, precise estimates couldn’t be obtained attributable to considerable heterogeneity, unexplainable by antibody titers.

Variability in vaccine effectiveness could result from differences in RCT design, population characteristics, sample sizes, detection of outcomes, and days elapsed since vaccination, quite than vaccine types. The findings indicated that COVID-19 vaccines were inadequately efficacious in stopping SARS-CoV-2 infections and thus, other anti-SARS-CoV-2 therapeutics are required for COVID-19 mitigation. Vaccine-induced immunity waning highlighted the importance of dosing intervals relative to anticipated viral outbreaks.