Predictive efficacies of vaccine dose fractionation using neutralizing antibody levels

Background With the emergence of SARS-CoV-2 variants that eluded immunity from vaccines and prior infections, vaccine shortages and their effectiveness pose unprecedented challenges for governments to expand booster vaccination programs. Fractionation of vaccine doses might be an effective strategy to help society to face these challenges, which may have comparable efficacies in contrast with the standard doses. Methods In this study, we analyzed the relationship between in-vitro neutralization levels and the observed efficacies against asymptomatic and symptomatic infection of ten types of COVID-19 vaccines using data from 13 studies from vaccination and convalescent cohorts. We further projected efficacies for fractional doses based on 51 studies included in our systematic review. Results By comparing with the convalescent level, vaccine efficacy increases from 8.8% (95% CI: 1.4%, 16.1%) to 71.8% (95% CI: 63.0%, 80.7%) against asymptomatic infection, and from 33.6% (95% CI: 23.6%, 43.6%) to 98.6% (95% CI: 97.6%, 99.7%) against symptomatic infection, respectively, along with the mean neutralization level from 0.1 to 10 folds of convalescent level. And mRNA vaccines provide the strongest protection, and decrease slowly for fractional dosing between 50% and 100% dosage. Conclusions Our results are consistent with studies for immune protection from COVID-19 infection. Based on our study, we expect that fractional dose vaccination could provide a partial immunity for SARS-CoV-2 virus. Fractional doses of vaccines could be a viable vaccination strategy compared to full-dose vaccination and deserves further exploration. Key points We analyzed the relationship between neutralization levels and efficacies against asymptomatic and symptomatic infection of ten types of COVID-19 vaccines from convalescent cohorts. Fractional doses of vaccines could be a viable strategy compared to full-dose vaccination and deserves further exploration. ### Competing Interest Statement BJC reports honoraria from AstraZeneca, Fosun Pharma, GlaxoSmithKline, Moderna, Pfizer, Sanofi Pasteur, and Roche. The authors report no other potential conflicts of interest. ### Funding Statement We acknowledge the financial support from the AIR@InnoHK Programme from Innovation and Technology Commission of the Government of the Hong Kong Special Administrative Region. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data are collected from open source with a detailed description in the Methods section.