July 23, 2021

expert reaction to preprint from PITCH study looking at interval between two Pfizer vaccine doses, and antibody and T-cell responses

A preprint, an unpublished non-peer reviewed paper from the PITCH study, looks at sustained T cell immunity, protection and boosting using extended dosing intervals of Pfizer-BioNTech COVID-19 vaccine.

This Roundup accompanied an SMC Briefing.

Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice, Immediate past Chair of the BMA Public Health Medicine Committee, said:

“The UK decision to use an extended interval between the two doses of the vaccines at the start of this year drew a lot of criticism, because it diverged from the interval used in the phase III studies¹.  The main reason for this decision was that it had become apparent for the variants circulating at that time, a single dose of vaccine provided most of the protection, and the second one just topped it up a little more.  (This remained true until the delta variant became prominent – with this variant, a single dose is considerably less effective, although two doses are almost as effective as against previous variants.)

“Such criticism did not, however, come from vaccinologists, because they know that longer prime-boost intervals are associated with an improved antibody response².

“This preprint provides a lot of detail, demonstrating that this is, as expected, the case with Covid-19 vaccines, as it is with other vaccines.

“The study – the “PITCH Consortium Study” is a sub-study of the larger SIREN study, which we have commented on previously^3,4.  While the SIREN study provides vital information on the real-world vaccine effectiveness in healthcare workers, the PITCH study looked at the findings from blood samples taken from vaccine recipients.

“It is, clearly, impossible to do such research with such large numbers of participants as the larger studies, such as the SIREN study; but such large numbers are not required.  The real-world effectiveness studies rely on people becoming ill (and most don’t, because of the vaccine), so very large numbers of participants are required to ensure enough of them become ill.

“By contrast, laboratory-based studies like this are looking at the antibody and other immune responses in the participants; and they will all have responded in some way, so each participant provides useful data, and thus the number of participants required for valid findings is much lower.

“The study showed the expected improvement to the immune response when a longer prime-boost interval was used.  In particular, there was a higher neutralising antibody response (although how long this will persist is not yet clear); and there were enhancements to the cellular immunity, in particular to the parts of the immune system that provide “immune memory”, so that there can be a vigorous and rapid response to exposure to the virus if it is encountered in the future. In other words, it is likely to extend the duration of efficacy of vaccination.

“As the authors remind us, while we tend to emphasise neutralising antibodies as a measure of the immune response (because they are important, but also because they are easy to measure), cellular immunity, which is harder to measure, is also likely to be very important, particularly as antibody levels decay after vaccination.

“While vaccinologists will not be surprised by the findings of this study, it is vital, particularly with a new virus and novel vaccination methods, to confirm that the vaccines are working as we would hope – and they are.”

References

1. English PMB. The UK’s vaccine approach isn’t ‘anti-science’. The Spectator 2021; Updated 04 Jan 2021; Accessed: 2021 (04 Jan): (https://www.spectator.co.uk/article/the-uk-s-vaccine-approach-isn-t-anti-science-).
2. English PMB. The UK approach to COVID-19 vaccination: why was it so different? Drugs in Context 2021;10:2021-4-5. (https://www.drugsincontext.com/the-uk-approach-to-covid-19-vaccination:-why-was-it-so-different/).
3. Wallace S, Hall V, Charlett A, Kirwan PD, Cole MJ, Shrotri M, et al. SIREN protocol: Impact of detectable anti-SARS-CoV-2 on the subsequent incidence of COVID-19 in 100,000 healthcare workers: do antibody positive healthcare workers have less reinfection than antibody negative healthcare workers? medRxiv 2020:2020.12.15.20247981. (https://www.medrxiv.org/content/medrxiv/early/2020/12/18/2020.12.15.20247981.full.pdf).
4. Hunter P, Riley E, Tang J, Altmann D, Young L, Wingfield T, et al. Expert reaction to a preprint from the SIREN study looking at SARS-CoV-2 infection rates in antibody positive healthcare workers. Science Media Centre 2021; Updated 14 Jan 2021; Accessed: 2021 (14 Jan): (https://www.sciencemediacentre.org/expert-reaction-to-a-preprint-from-the-siren-study-looking-at-sars-cov-2-infection-rates-in-antibody-positive-healthcare-workers/?cli_action=1610629285.674).

Preprint (not a paper): ‘Sustained T cell immunity, protection and boosting using extended dosing intervals of BNT162b2 mRNA vaccine’ by Rebecca P. Payne et al. was posted online at 00:01 UK time on Friday 23 July 2021.  This work is not peer-reviewed.

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Dr Peter English: “Dr English is on the editorial board of Vaccines Today: an unpaid, voluntary, position.”