COVID-19 Vaccine-Induced Immunity May Benefit From Extended Dosing Intervals

Researchers assessed reactogenicity and immune responses following COVID-19 vaccination in either a 4- or 12-week dosing interval.

Results of an exploratory analysis found that longer dosing intervals for the BNT162b2 COVID-19 vaccine may decrease the rate of immunogenicity decay. These findings were published in The Lancet Respiratory Medicine.

In this randomized, participant-masked immunogenicity trial, participants (N=730) were randomly assigned to receive the ChAdOx1 nCoV-19 or BNT162b2 COVID-19 vaccine, administered in either a heterologous or homologous schedule and in 4- or 12-week dosing intervals. Humoral and cellular responses, reactogenicity, and safety were evaluated at 28 days and 6 months after receipt of the second vaccine dose.

 Among all participants included in the study, the mean age was 58.2 years, 56% were men, and 77% were White. In addition, 22% of participants had cardiovascular-related comorbidities, 12% had respiratory-related comorbidities, and 4% had diabetes.

The 4-week dosing interval was favored among participants in the homologous ChAdOx1 nCoV-19 group in regard to cellular responses at 28 days (adjusted geometric mean ratio [aGMR], 0.67 spot-forming cells per million peripheral blood mononuclear cells [SFC/106 PBMC]) and at 6 months (aGMR, 0.34 SFC/106 PBMC). Similar findings were noted among participants in the heterologous ChAdOx1 nCoV-19 group for 28-day (aGMR, 0.59 SFC/106 PBMC) and 6-month (aGMR, 0.48 SFC/106 PBMC) cellular responses. BNT162b2 followed by ChAdOx1 at 28 days (aGMR, 0.35 SFC/106 PBMC) and six months (aGMR, 0.33 SFC/106 PBMC), and homologous BNT162b2 recipients at 28 days (aGMR, 0.64 SFC/106 PBMC; 95% CI, 0.43-0.96).

In regard to pseudotype virus neutralizing antibody responses at 28 days, the 12-week interval was favored among participants in the homologous ChAdOx1 nCOV-19 group (aGMR, 2.35), followed by those in the heterologous ChAdOx1 nCOV-19 (aGMR, 1.47), heterologous BNT162b2, (aGMR, 1.44), and homologous BNT162b2 (aGMR, 1.62) groups.

For anti-spike immunoglobin G responses, the 12-week interval was favored among participants in the homologous ChAdOx1 nCoV-19 group at both 28 days (aGMR, 1.61) and six months (aGMR, 1.80). Similar findings were observed in participants in the homologous BNT162b2 group at both 28 days (aGMR, 1.24) and at 6 months (aGMR, 1.75), and among those in the heterologous BNT162b2 group at 28 days (aGMR, 1.37).

The frequency of most systemic solicited adverse events was significantly decreased among participants who received the BNT162b2 vaccine as a second dose at 12 weeks.

A total of 40 participants tested positive for COVID-19 infection within the follow-up period, none of whom required hospitalization. Of these participants, 11 were in the homologous ChAdOx1 nCoV-19 group, 9 were in the homologous BNT162b2 group, 9 were in the heterologous ChAdOx1 nCoV-19 group, and 7 were in the heterologous group.

Limitations included the inability to evaluate the effectiveness of each vaccine due to the small sample sizes, study design, and the small number of patients who tested positive for COVID-19 infection.

According to the researchers, “[this] study suggests that the choice of vaccines used in a COVID-19 priming schedule had a greater effect on immunogenicity than the dose interval.”

Disclosure: Multiple authors declared affiliations with industry. Please see the original reference for a full list of disclosures.


Shaw RH, Liu X, Stuart ASV, et al. Effect of priming interval on reactogenicity, peak immunological response, and waning after homologous and heterologous COVID-19 vaccine schedules: exploratory analyses of Com-COV, a randomised control trial. Lancet Respir Med. 2022;S2213-2600(22)00163-1. doi:10.1016/S2213-2600(22)00163-1