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. 2023 Jun;9(6):e17259.
doi: 10.1016/j.heliyon.2023.e17259. Epub 2023 Jun 13.

Effect of vaccine dosing intervals on Omicron surrogate neutralization after three doses of BNT162b2

Martin A Prusinkiewicz  1 , Sadaf Sediqi  2 , Ying Jie Li  1 , David M Goldfarb  2 , Michael Asamoah-Boaheng  3 , Nechelle Wall  4 , Pascal M Lavoie  1 , Brian Grunau  3   5   4
Affiliations

Effect of vaccine dosing intervals on Omicron surrogate neutralization after three doses of BNT162b2

Martin A Prusinkiewicz et al. Heliyon. 2023 Jun.

Abstract

Background: Increasing the interval between the first and second SARS-CoV-2 vaccine doses enhances vaccine immunogenicity, however the optimal timing of the third vaccine is unknown. In this study, we investigated how the time interval between the first and second (V1-V2), or second and third (V2-V3) doses affects immunogenicity after three doses of the BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine.

Methods: This is an observational cohort consisting of 360 participants enrolled in the COVID-19 Occupational Risks, Seroprevalence, and Immunity among Paramedics in Canada (CORSIP) study. Immune responses to BA.1 and other variants were measured from serum using an ACE2 competitive binding assay for surrogate SARS-CoV-2 neutralization. We fit a multiple linear regression model to estimate the independent association between both the V1-V2 and V2-V3 intervals and serum SARS-CoV-2 neutralization, while adjusting for age, sex, and the V3-to-blood collection interval. We examined vaccine dosing intervals as continuous variables and categorized them into quartiles.

Results: The mean age was 40 years, 45% were female sex (at birth), and the median BA.1 surrogate neutralization was 61% (IQR 38-77%). The multivariate analysis indicated that longer V1-V2 (β = 0.1292, 95% CI: 0.04807-0.2104) and V2-V3 (β = 0.2653, 95% CI: 0.2291-0.3015) intervals were associated with increased surrogate neutralization of BA.1. These results were consistent when examining responses against Spike from other SARS-CoV-2 strains. When categorized into V2-V3 quartiles, the first (56-231 days), and second (231-266 days) quartiles demonstrated decreased BA.1 surrogate neutralization compared to the longest V2-V3 quartile (282-329 days). There was no significant difference in surrogate neutralization between the long (266-282 days) and longest (282-329 days) V2-V3 intervals.

Conclusion: Longer intervals between first, second and third doses are independently associated with increased immunogenicity for all tested SARS-CoV-2 strains. Increasing the intervals between the second and third vaccine doses up to 8.9 months provided additive benefits increasing the immunogenicity of BNT162b2 vaccine schedules.

Keywords: COVID; Immunization; SARS-CoV-2; Surrogate neutralization; Vaccine interval.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brian Grunau reports financial support was provided by Government of Canada. Brian Grunau reports financial support was provided by Michael Smith Foundation for Health Research. Mohammad E. Karim reports financial support was provided by Michael Smith Foundation for Health Research. Michael Asamoah-Boaheng reports financial support was provided by Michael Smith Foundation for Health Research. Martin Prusinkiewicz reports financial support was provided by Canadian Institutes of Health Research.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Surrogate neutralization of SARS-CoV-2 variants in participants with three doses of BNT16b2. All variants were significantly different from one another (p < 0.0001), except for the comparisons of % surrogate neutralization for B.1.351 when compared to P.1 and B.1.1.7 when compared to B.1.617.2, which were not significantly different (ns). The median and interquartile ranges are presented for each variant.
Fig. 2
Fig. 2
Surrogate neutralization of different SARS-CoV-2 variants with dosing interval. (A) Surrogate neutralization of SARS-CoV-2 variants in individuals with three doses of BNT16b2 stratified by the interval between their first and second doses, V1–V2. BA.1 showed a statistically significant decrease in % surrogate neutralization in the V1–V2 longest quartile which represents the longest V1–V2 interval, when compared to the shortest V1–V2 interval in the first quartile. (B) Surrogate neutralization of SARS-CoV-2 variants in individuals with three doses of BNT16b2 stratified by the interval between their second and third doses, V2–V3. The two shortest V2–V3 intervals, represented by the first and second quartiles had significantly lower surrogate neutralization for all variants when compared to the longest interval for that variant. The median and interquartile ranges are presented for each variant in each group. * Denotes significant difference when compared to Q4 according to a Dunn's Test followed by a Benjamini Hochberg procedure where the FDR cut off is 0.1.
See this image and copyright information in PMC

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