Split dosing of COVID-19 vaccines provides antibody responses
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Key takeaways:
- All the subjects regardless of dosing experienced significant increases in postvaccination mean fluorescent immunity levels of receptor binding domain (RBD) protein and spike protein 1 (S1).
- Patients receiving split and conventional doses experienced no differences in antibody responsiveness for RBD or S1.
- Participants tolerated split dosing well without any significant adverse events.
Split doses of COVID-19 vaccines were able to provide antibody responsiveness among patients with allergic reactions to previous doses, according to a letter published in Annals of Allergy, Asthma & Immunology.
Also, no significant adverse events occurred with split dosing, which was well tolerated, Jill A. Poole, MD, FAAAAI, FACAAI, division chief of allergy and immunology at the University of Nebraska Medical Center, and colleagues wrote.
“This study was prompted by our early experience with COVID-19 vaccine administration concerns with employee referrals at our institution,” Poole said.
When emergency use authorization was first granted to COVID-19 vaccines for use in health care personnel, Poole said, there were employee concerns about potential vaccine allergies and reactions to the first dose.
“Thus, we instituted a protocol with an option to administer the second vaccine using split dosing with additional precautions, allowing premedication with acetaminophen and/or antihistamines,” Poole said.
When this protocol was well tolerated, Poole continued, the researchers presented the results of their work to the American Academy of Allergy, Asthma & Immunology.
“However, it was not known whether split dosing of the vaccine would provide the same level of antibody immunity as conventional dosing. Thus, we designed this current study to answer that question,” Poole said.
The study’s design and results
The researchers offered conventional or split doses of COVID-19 vaccines to adults aged 21 to 63 years (mean age, 43.3 years) with prior allergic reactions to COVID-19 vaccination at a tertiary care institution between November 2021 and March 2022.
Vaccinations included the Pfizer booster (73.3%), Pfizer two-part series (10%), Moderna booster (3.3%) and Johnson & Johnson’s Janssen (13.3%). The split dose consisted of a first 0.05 mL injection, followed by the remainder of the dose.
Patients also were offered 500 mg of acetaminophen and 10 mg of cetirizine to attenuate potential pain, itching, rash, headache and other adverse effects. Everyone in the split dose group and one of the participants in the full dose group took antihistamine and acetaminophen before receiving the vaccine.
Blood was collected from 30 participants, including 15 receiving a split dose and 15 receiving a full dose, at enrollment and 6 weeks after vaccination.
The researchers said they found significant increases in postvaccination mean fluorescent intensity (MFI) levels of receptor binding domain (RBD) protein (P < .001) and spike protein 1 (S1; P < .001) as well as no differences in nucleocapsid antibody levels.
Similarly, the researchers did not find any differences in antibody responsiveness, or fold-change, for RBD and S1 between the conventional dose and split dose groups.
Positive nucleocapsid antibody seroconversion was present in three of the participants, indicating that natural infection or immunity could account for the increases in RBD and S1 antibody levels, according to the researchers.
But when the researchers removed these three participants from their analysis, significant increases in postvaccination levels of RBD and S1 remained in both groups without any differences in fold-change responsiveness.
Further, the researchers found increases in RBD and S1 antibody expression following vaccination when they assessed results by the type of vaccine that was received.
At baseline, seven of the participants who received a conventional dose and three of those who received a split dose had positive nucleocapsid MFI levels exceeding 700, which is the cutoff for a positive specimen.
However, these participants experienced decreases in their nucleocapsid antibody levels during the study period, with mean MFI levels of 4,167 (standard error of the mean [SEM], 1320) before vaccination and 2,591 (SEM, 983) afterward (P = .01).
Headache, fatigue, numbness/tingling, facial flushing and pruritus were reported by four of the participants, although no significant adverse events occurred, and the split dosing was well tolerated, the researchers said.
Conclusions and next steps
“We had hypothesized that there would be no difference in antibody responses to split dosing versus conventional (full) dosing of the vaccine,” Poole said.
“We were pleased that the data demonstrated similar responses to suggest that this approach could be used in patients with vaccine hesitancy for additional safety precautions if deemed necessary,” she continued.
Based on these results, the researchers concluded that split dosing is effective in providing antibody responsiveness. Also, Poole said, this protocol may help patients overcome any vaccine hesitancy they may feel.
“In patients who are vaccine hesitant because of allergy concerns or concerns about reacting to the vaccine, doctors could administer a smaller test dose of the vaccine, observe for 30 minutes and then administer the remaining dose,” Poole said. “This may give additional peace of mind to patients who want the vaccine but are fearful.”
Further, the researchers recommended that future studies could assess antibody responses at other time points, other immune measures and inclusion of more diverse patient populations.
“We did not study antibody responsiveness to vaccine in children, the elderly or those with underlying health issues, yet we would anticipate similar findings,” Poole said.
Studies of other approaches for improving safety and minimizing the mild reactions that some patients do experience with vaccines, including pretreatment options, would be warranted as well, Poole said.
“It should be noted that the COVID-19 vaccine is very safe, and the vast majority of people would not need this approach,” Poole said. “This approach is for those who are worried, hesitant, and/or concerned, and who still want to get protected against the COVID-19 pandemic.”
For more information:
Jill A. Poole, MD, can be reached at japoole@unmc.edu.