One of the most in-depth studies into COVID-19 immune response to vaccines to date shows a short and long dosing interval of the Pfizer jab generated strong antibody and T cell immune responses, reports MedicalBrief.
The study, says Dr Rebecca Payne, study author from Newcastle University, one of the higher education institutions involved in the research, is one of the most comprehensive assessments of the immune response to COVID-19 following two doses of the Pfizer vaccine
The study found T cell levels are well-maintained and antibody levels are higher after a longer interval between the first and second dose of the Pfizer vaccine, despite a significant drop in antibody levels between doses.
Importantly, worldwide studies are showing that both the short and long dosing schedules lead to strong real-world protection against COVID-19, emphasising the importance of having a second dose of the vaccine.
The Protective Immunity from T cells to COVID-19 in Health workers study (PITCH) examined how antibody and T cell levels change over time after either a ‘short’ (three–four weeks, average of 24 days) or ‘long’ (six–14 weeks, average of 70 days) interval between the first and second dose of the Pfizer vaccine.
Payne said: “We found an interesting pattern in the levels of immune cells present. Our study provides reassuring evidence that both dosing schedules generate robust immune responses against the virus after two doses.
"For the longer schedule, the antibody levels dropped off between first and second dose, which included the loss of any neutralising effect against the Delta variant. However, T cell responses were consistent, indicating they may contribute to important protection against COVID-19 during this time.
"After the second dose on the longer dosing schedule, antibody levels surpassed those seen at the same time-point after a shorter dosing interval. Although T cell levels were comparatively lower, the profile of T cells present suggested more support of immune memory and antibody generation.
"We now need to carry out more follow up studies to understand the full clinical significance of our findings.”
A total of 503 healthcare workers were recruited to the study, of whom 223 (44%) had previously had COVID-19.
Key findings of the study are:
* For the longer dosing interval, antibody levels fell noticeably between the first and second dose when tested in the lab. In particular, neutralising antibody levels against the Delta variant were poorly induced after a single dose, and not maintained during the interval before the second dose. T cells were well-maintained between the first and second dose.
* After two vaccine doses, neutralising antibody levels were twice as high after the longer dosing interval compared with the shorter dosing interval.
* After two doses, overall T cell levels were 1.6 times lower after the long compared with the short dosing schedule. However, after the longer dosing interval, a higher proportion of T cells present were ‘helper’ T cells, which are important for long-term immune memory and helping generate antibodies to prevent infection.
* The longer dosing interval resulted in higher neutralising antibody levels, after the second dose, against the Delta variant and all other Variants of Concern tested.
Regardless of the dosing schedule, the study, led by the University of Oxford with the universities of Newcastle, Liverpool, Sheffield and Birmingham, with support from the UK Coronavirus Immunology Consortium, found levels of antibodies and T cells varied significantly from person to person, which may depend on genetics, underlying health conditions and past exposure to Covid-19 and other viruses.
This underlies the importance of everyone getting two doses of the vaccine to maximise their own protection, particularly against Variants of Concern. Follow up of this cohort six and 12 months after vaccination is needed to investigate longer term immune response, as well as whether it translates to lower or less severe infection rates.
Real world data from Public Health England demonstrates the Pfizer Covid-19 vaccine is effective at reducing levels of serious disease, hospitalisation and death, even after one dose. Understanding the underlying immune response generated by different dosing schedules will help maximise future protection, tackle new Variants of Concern and prevent reinfections.
Dr Christopher Duncan, from Newcastle University and Honorary Consultant from Newcastle upon Tyne Hospitals NHS Foundation Trust, said: "We are proud in Newcastle to be playing an important role in the PITCH consortium, which continues to deliver fresh insights into the immune response to Covid-19 vaccination."
Sustained T cell immunity, protection and boosting using extended dosing intervals of BNT162b2 mRNA vaccine
Rebecca P. Payne, Stephanie Longet, James A. Austin, Donal T. Skelly, Wanwisa Dejnirattisai , Sandra Adele, Naomi Meardon, Sian Faustini, Saly Al-Taei, Shona C. Moore, Tom Tipton, Luisa M Hering, Adrienn Angyal, Rebecca Brown, Natalie Gillson, Susan L Dobson, Ali Amini, Piyada Supasa, Andrew Cross, Gurjinder Sandhar, Jonathan A. Kilby, Jessica K Tyerman, Alexander R Nicols, Thomas Altmann, Hailey Hornsby, Rachel Whitham, Eloise Phillips, Tom Malone, Alexander Hargreaves, Adrian Shields, Ayoub Saei, Sarah Foulkes, Lizzie Stafford, Sile Johnson, Daniel G. Wootton, Christopher P. Conlon, Katie Jeffery, Philippa C. Matthews, John Frater, Alexandra S. Deeks, Christina Dold, Andrew J. Pollard, Anthony Brown, Sarah L. Rowland-Jones, Juthathip Mongkolsapaya, Eleanor Barnes, Susan Hopkins, Victoria Hall, Christopher JA Duncan, Alex Richter, Miles Carroll, Gavin Screaton, Thushan I. de Silva, Lance Turtle, Paul Klenerman, Susanna Dunachie
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. In a study of 503 healthcare workers, we show that after priming following the first vaccine there is a marked decline in SARSCoV-2 neutralising antibody (NAb) levels, but, in contrast, a sustained T cell response to spike protein. This divergent immune profile was accompanied by robust protection from infection over this period from the circulating alpha (B.1.1.7) variant.
Importantly, following the second vaccine dose, NAb levels were higher after the extended dosing interval (6-14 weeks) compared to the conventional 3-4 week regimen, accompanied by a clear enrichment of CD4+ T cells expressing IL2.
These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective, immunogenic protocol and that antiviral T cell responses are a potential mechanism of protection.
A single dose of BNT162b2 is associated with sustained protection against infection over an extended dosing interval. To demonstrate the impact of the extended dosing interval on vaccine effectiveness against infection, we include data from the entire SIREN cohort. (This study undertook clinical follow-up of 25,066 healthcare workers (HCWs) between 7 December to 12 March 2021, with asymptomatic screening over a period of up to 95 days from the first dose of BNT162b2.)
At this time, the Alpha (B.1.1.7) variant was the dominant circulating virus in the UK, as confirmed by the Public Health England (PHE) sequencing programme.
These data are derived from careful, prospective follow up of the cohort. The time-resolved data show a gradual increase in the estimate of protection against all infection (asymptomatic and symptomatic) afforded by the vaccine following the single dose in individuals who were seronegative prior to vaccination.
A hazard ratio for infection of less than 50% is reached after about 14 days, with protection maintained at high levels until second dose, and then until the end of the follow up period (although with wide confidence intervals due to decreasing numbers).
The hazard ratios are adjusted (including for age, ethnicity, comorbidities, and region), and the lower hazard ratio seen on days 0-3 is explained by deferral of vaccination in symptomatic individuals.
Overall, these data show robust protection against infection following the first dose of BNT162b2, with vaccine effectiveness reaching 72% by three weeks after dose 1 and maintained after that point.
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