July 23rd, 2021

Our latest publication looks at whether the immune response to the Pfizer COVID-19 vaccine is different depending on the number of weeks between the two doses.

We studied 503 healthcare workers in Birmingham, Liverpool, Newcastle, Oxford and Sheffield, comparing short (median 3.4 weeks, range 2-5 weeks) and long (median 10 weeks, range 6-14 weeks) dosing schedules of the Pfizer vaccine. This is one of the most comprehensive studies into the immune response to COVID-19 vaccines outside of a clinical trial to date.

• We found that for people getting the longer dosing interval, antibodies fell over the 10 weeks after the first dose, but T cell levels were well-maintained. We know that a single dose of vaccine gives significant protection against COVID-19, so T cells may be an important part of the mechanism.
• The long dosing interval resulted in 2x higher neutralising antibodies against all variants of the virus tested, including the Delta variant, compared to the short dosing interval. Absolute numbers of T cells to spike were lower after the long interval compared to the short one, but the T cell response had more characteristics of a helper response promoting long term memory and antibody production.
• Regardless of the dosing schedule, the study found levels of antibodies and T cells varied from person to person, which may depend on genetics, underlying health conditions, and past exposure to COVID-19 and other viruses. This means our study is more relevant at a population level than for individual people, and underlies the importance of everyone getting two doses of the COVID-19 vaccine to maximise their own protection, particularly against Variants of Concern.

Professor Susanna Dunachie from University of Oxford said:
“Our study aimed to shine a light on the different type of immune cells involved to help us better understand the potential mechanisms of protection, particularly against new Variants of Concern. It is clear from our findings that to maximise your individual protection, it is very important to get two doses of the COVID vaccine when offered”.

Our grateful thanks go to all the healthcare workers who volunteered to take part in this study. Click here to read the pre-print with additional figures and methods here.

June 16th, 2021

The latest work from the PITCH study looks at the trajectory of the immune response to SARS-CoV-2 after COVID-19 infection. .

We followed a cohort of 78 healthcare workers in detail at 5-6 time points each over a six-month period before vaccines were available, and used a machine learning approach to predict response at 6 months after infection. We looked at important questions such as if natural infection provides protection against variants of concern and if there is any correlation between the severity of your symptoms and your long-term immunity. The results showed a high degree of variability amongst participants’ immune responses. 6 months after infection, the participants were defined as either high responders or low responders using SIMON, a machine learning approach.
Using SIMON, researchers identified an early immune signature associated with durable and protective immunity against SARS-CoV-2. Both, cellular and humoral immune responses mounted one month after infection were identified to be important for maintenance of immunity 6 months after infection. Moreover, those individuals were also better able to neutralise both the Victoria strain, and alpha and beta variants of concerns. On the other hand, those that were identified as low responders showed a reduction in the capacity to neutralise the Victoria strain, with a severe loss of neutralisation against both VOC. All the data in this paper combined tells us that immune events primed during early SARS-CoV-2 infection may define the subsequent trajectories leading to the effective maintenance or loss of long-term T and B cell immune memory. Importantly, maintenance of immune memory over time is critically required for effective neutralisation of variants of concern.

Professor Eleanor Barnes from University of Oxford said:
"Gaining a detailed understanding of the immune response after COVID-19 infection is critical in allowing us to reduce reinfection, tackle variants and to helping us to design future vaccination strategies. "

Click here to read the pre-print with additional figures and methods here

March 29th, 2021

PITCH study finds strong immune response following first dose of COVID-19 vaccination.

The latest publication to come out of the PITCH study has found that 99 per cent of people generate a robust immune response against Covid-19 after just one dose of the Pfizer vaccine. It suggests one dose of the vaccine protects against severe disease, supporting the decision to delay the second dose and provide protection to as many higher-risk groups as possible by providing more first doses. The study showed after two doses levels of protection were even stronger, underlining the importance of people coming forward for their second dose.

Click here for the full article

February 23rd, 2021

Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera.

The race to produce vaccines against SARS-CoV-2 began when the first sequence was published, and this forms the basis for vaccines currently deployed globally. Independent lineages of SARS-CoV-2 have recently been reported: UK, B.1.1.7; South Africa, B.1.351; and Brazil, P.1. These variants have multiple changes in the immunodominant spike protein that helps the virus to enter cells and mutations in this site are of great concern for their potential for immune escape. This paper describes a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccine serum samples. It showed that receptor-binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization. In several cases, it would appear that convalescent and some vaccine serum offer limited protection against this variant.

November 11th, 2021

Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine.

Payne*, R.P., Longet*, S., Austin*, J.A., Skelly*, D., Dejnirattisai, W… Duncan C.J.A., Richter, A.G.., Carroll, M.W., Screaton, G., de Silva, T., Turtle, L., Klenerman, P., & Dunachie S.J et al., (2021)

Cell 184, 1-16. (2021).

View full article: https://doi.org/10.1016/j.cell.2021.10.011

January 1st, 2022

T-Cell and Antibody Responses to First BNT162b2 Vaccine Dose in Previously SARS-CoV-2-Infected and Infection-Naive UK Healthcare Workers: A Multicentre, Prospective, Observational Cohort Study.

Angyal*, A., Longet*, S., Moore*, S.C., Payne* R.P., Harding*, A.C.,… Klenerman P., Dunachie S., Richter A.G., Duncan C.J.A., Barnes E., Carroll M.W., Turtle L., & de Silva T et al.

The Lancet Microbe

View full article: https://doi.org/10.1016/S2666-5247(21)00275-5

August 17th, 2021

Two doses of SARS-CoV-2 vaccination induce more robust immune responses to emerging SARS-CoV-2 variants of concern than does natural infection.

Skelly*, D.T., Harding*, A.C., Gilbert-Jaramillo, J., Knight, M.L., Longet, S., … Klenerman, P., Dunachie, S.J., Barnes, E., Carroll, M., W & James, W., S

Nature Communications 12, 5061 (2021).

View full article: https://doi.org/10.1038/s41467-021-25167-5

March 10th, 2022

Divergent trajectories of antiviral memory after SARS-CoV-2 infection

Tomic*, A., Skelly*, D.T., Ogbe*, A., O’Connor*, D., Pace, M., Adland, E., … Carroll, M.W., James, W., Klenerman, P., Barnes, E., Dold, C., & S. Dunachie, S.J.

Nature Communications 13, 1251 (2022).

View full article: https://doi.org/10.1038/s41467-022-28898-1

April 6th, 2021

T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses.

Ogbe* A, Kronsteiner* B, Skelly* DT, Pace* M, Brown*, A., Adland*. E., … Turtle, L., Klenerman, P., Goulder, P., Frater, J., Barnes, E., & Dunachie S.

Nature Communications 2021; 12(1): 2055;

View full article: https://doi.org/10.1038/s41467-021-21856-3

March 25th, 2021

T-Cell and Antibody Responses to First BNT162b2 Vaccine Dose in Previously SARS-CoV-2-Infected and Infection-Naive UK Healthcare Workers: A Multicentre, Prospective, Observational Cohort Study.

Angyal et al., (2021)

The Lancet Pre-Print Server

View full article: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3812375

February 23rd, 2021

Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera.

Zhou et al., (2021)

Cell

View full article: https://www.sciencedirect.com/science/article /pii/S0092867421002269

February 18th, 2021

Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera.

Supasa et al., (2021)

Cell

View full article: https://www.sciencedirect.com/science/article /pii/S0092867421002221

February 9th, 2021

Vaccine-induced immunity provides more robust heterotypic immunity than natural infection to emerging SARS-CoV-2 variants of concern.

Skelly et al., (2021)

Research Square

View full article: https://www.researchsquare.com/article/rs-226857/v1