Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine. Payne et al.

Overview

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the UK to accelerate
population coverage with a single dose. At this time, trial data was lacking, and we addressed this in a study of UK
healthcare workers. We aimed to describe the dynamics of T cell and Ab responses after the first dose of BNT162b2 mRNA
vaccine over an extended dosing interval, and to compare the magnitude of Ab and T cell responses 4 weeks after dose 2
between short and long vaccination regimens.

Human sample and metadata collection

HCWs were recruited into the PITCH study at NHS hospitals in five centres in England. All participants received the BNT162b2
Pfizer/BioNTech vaccine at either the "short" dosing interval (3-5 weeks) or "long" dosing interval (6-14 weeks). Peripheral blood was
collected and peripheral blood mononuclear cells (PBMCs) and plasma were stored by cryopreservation at -140 oC and -80 oC
respectively. Participants were identified as those with samples collected at timepoints of interest (n=589 participants).

Long dosing interval accepted timepoints included;
- baseline (anytime prior to first dose of vaccine)
- 28 days after first vaccine dose (+/- 7 days)
- 70 days after first vaccine dose (minimum accepted 40 days. IQR 62/75, range 41 - 129 days),
- 28 days after the second vaccine dose (+/- 7 days)
- 90 days after the second dose (+/- 7 days)

Short dosing interval accepted timepoints included;
- baseline (anytime prior to first dose of vaccine)
- 7 days after second dose (+ 7days)
- 28 days after the second vaccine dose (+/- 7 days)
- 90 days after the second dose.

Clinical metadata collected included BNT162b2 immunisation dates, date of any prior SARS-CoV-2 infection defined by a positive
PCR test and/or detection of antibodies to spike or nucleocapsid protein, presence or absence of symptoms, time between
symptom onset and sampling, age, gender and ethnicity of participant. Other metadata included location of study centre.
De-identified limited metadata are available here. Options to explore detailed metadata can be sought by contacting the lead author
(Paul Klenerman).

Data collection

Serology and Cellular data were collected from assays using plasma and PBMCs respectively.
Serology:
MSD and ACE2 assay - Two wells run per test; 1:1000 and 1:10,000 dilution
Neutralizing Ab - Serial dilutions were run per test to calculate reduction in number of infected foci - FRNT50

Cellular:
ELISpot - Two or three wells run per test ; mean is shown with background subtraction. Total Spike is calculated by
adding data from Spike 1 and Spike2
ICS - One run per test compared to positive and negative controls.

Results
These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective, immunogenic protocol