PUBLICATIONS

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.

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.

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


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..

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


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

The scale of the pandemic and error-prone virus replication is leading to the appearance of mutant viruses leading to one of the biggest questions in the pandemic, can these new viruses escape from antibody responses? This paper examines the ability of B.1.1.7, commonly known as the Kent variant, to evade antibody responses elicited by natural SARS-CoV-2 infection or vaccination. Analysis of the variant revealed that B.1.1.7 is harder to neutralize than parental virus, compromising neutralization by a class of public antibodies. However, widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed.

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


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

Both natural infection with SARS-CoV-2 and immunization with a number of vaccines induce protective immunity. However, the ability of such immune responses to recognize and therefore protect against emerging variants is a matter of increasing importance. Such variants of concern (VOC) include isolates of lineage B1.1.7, first identified in the UK, and B1.351, first identified in South Africa. Our data confirm that VOC, particularly those with substitutions at residues 484 and 417 escape neutralization by antibodies directed to the ACE2-binding Class 1 and the adjacent Class 2 epitopes but are susceptible to neutralization by the generally less potent antibodies directed to Class 3 and 4 epitopes on the flanks RBD. To address this potential threat, we sampled a SARS-CoV-2 uninfected UK cohort recently vaccinated with BNT162b2 (Pfizer-BioNTech, two doses delivered 18-28 days apart), alongside a cohort naturally infected in the first wave of the epidemic in Spring 2020...(cont)

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


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

A major issue in identification of protective T cell responses against SARS-CoV-2 lies in distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity generated by exposure to other coronaviruses. We characterised SARS-CoV-2 T cell immune responses in 168 PCR-confirmed SARS-CoV-2 infected subjects and 118 seronegative subjects without known SARS-CoV-2 exposure using a range of T cell assays that differentially capture immune cell function. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) were found in those who had been infected by SARS-CoV-2 but were rare in pre-pandemic and unexposed seronegative subjects. However, seronegative doctors with high occupational exposure and recent COVID-19 compatible illness showed patterns of T cell responses characteristic of infection, indicating that these readouts are highly sensitive. By contrast, over 90% of convalescent or unexposed people showed proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations...(cont)

View full article: https://www.medrxiv.org/content/10.1101/2020.09.28.20202929v1


Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses...(cont)

View full article: https://www.nature.com/articles/s41590-020-0782-6