SPLIT-DOSING OF COVID-19 VACCINES IS SAFE AND PROVIDES NON-INFERIOR ANTIBODY RESPONSIVENESS TO CONVENTIONAL VACCINE DOSING

INTRODUCTION: Vaccination has proven efficacy against COVID-19, yet allergic or adverse reactions have resulted in vaccine hesitancy nationwide. Graded or split dosing of vaccines is a relatively common allergy practice that is understudied for efficacy, particularly for COVID-19. We aimed to compare antibody responsiveness and safety of split versus conventional dosing of COVID-19 vaccines. METHODS: A total of 30 adult subjects received conventional/full (N=15) or 2-step split (N=15) dosing of a COVID-19 vaccine. Pre- and 6-week post-serum antibody levels were determined by multiplex, microsphere-based IgG quantitative assays for SARS-CoV-2 antigens including Receptor Binding Domain (RBD), Spike protein 1 (S1), and nucleocapsid (natural infection marker). The majority received Pfizer booster (73%). Any adverse reactions were recorded. RESULTS: Post-vaccine RBD and S1 (but not nucleocapsid) antibody expression as measured by mean fluorescent intensity increased in conventional (p=0.0006 and p=0.0054, respectively) and split (p<0.0001 and p=0.0002) dosed subjects. Findings persisted after removal of 3 subjects with evidence of new natural infection as determined by nucleocapsid antibody positive conversion. There was no difference in mean fold-change (post/pre) antibody expression for RBD (conventional: +5.3 vs. split: +26.7, p=0.22) and S1 (+11.7 vs. +27.3, p=0.26). Split dosing was overall well-tolerated with minimal adverse reactions. CONCLUSION: Split dosing is safe and non-inferior in efficacy as evidenced by antibody responsiveness when compared to conventional dosing of the COVID-19 vaccines. This approach could be applied to persons with vaccine hesitancy of various reasons including allergic disease(s) to provide immunization against this pandemic and be modeled in future pandemic scenarios.