COVID-19 Vaccine Split-Dosing Proves Safe, Noninferior to Conventional Dosing

Split dosing vaccination may be a viable alternative for those with vaccine hesitancy due to allergic disease or for other reasons.

COVID-19 vaccination split dosing is noninferior in efficacy and safety compared with conventional dosing, according to study findings presented at the American College of Allergy, Asthma & Immunology (ACAAI) 2022 Annual Scientific Meeting, held from November 10 to 14, in Louisville, Kentucky.

According to study authors, “Graded or split dosing of vaccines is a relatively common allergy practice that is understudied for efficacy, particularly for COVID-19.” The researchers therefore sought to compare split vs conventional dosing of COVID-19 vaccines with respect to antibody responsiveness and safety.

The investigators conducted a prospective study of 30 adult participants, with 15 receiving conventional/full dosing of a COVID-19 vaccine and 15 participants receiving 2-step split dosing of a COVID-19 vaccine. Multiplex microsphere-based immunoglobulin G quantitative assays for SARS-CoV-2 antigens including receptor binding domain (RBD), spike protein 1 (S1), and nucleocapsid were used to determine pre- and 6-week post-serum antibody levels. Notably, 73% of participants received the Pfizer booster.

Graded or split dosing of vaccines is a relatively common allergy practice that is understudied for efficacy, particularly for COVID-19.

Researchers found post-vaccine RBD and S1 antibody expression increased in conventional-dose participants (RBD, P =.0006; S1, P =.0054) and in split-dose participants (RBD, P <.0001; S1, P =.0002) measured by mean fluorescent intensity. Moreover, after 3 participants with evidence of new natural infection determined by nucleocapsid antibody positive conversion were removed from analysis, their findings were unchanged.

No difference was seen in mean fold-change (post/pre) antibody expression for RBD (conventional 5.3 vs split 26.7; P =.22) and S1 (conventional 11.7 vs split 27.3; P =.26).

Researchers further reported that split dosing had minimal adverse reactions and was well-tolerated.

The researchers concluded that “Split dosing is safe and non-inferior in efficacy as evidenced by antibody responsiveness when compared to conventional dosing of the COVID-19 vaccines.” They believe this strategy 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.


Musa A, Wood M, May S, et al. Split-dosing of COVID-19 vaccines is safe and provides non-inferior antibody responsiveness to conventional vaccine dosing. Ann Allergy Asthma Immunol. 2022;125(5):S8. doi:0.1016/j.anai.2022.08.531