We used a validated SARS-CoV-2 pseudovirus neutralisation assay standardised against WHO research standards (the National Institute for Biological Requirements and Control) to calculate NAb titres.13 Our results revealed either undetectable antibodies or low NAb titres in immunodeficient outpatients, with only four (5%) of 80 showing detectable neutralisation of B.1.1.7 and two (3%) showing detectable neutralisation of B.1.351 (appendix). threat to general public health and the effectiveness of these vaccines. As of Jan 11, 2021, in the UK, the interval between the 1st and second dose of vaccination was prolonged to 12 weeks. This extension accomplished the aim of maximising human population protection by immunising the greatest possible number of individuals to prevent disease and hospital admissions. Encouragingly, a growing number of studies possess reported a designated reduction in the number of individuals with moderate-to-severe medical symptoms and a substantial decline in the number of hospitalised individuals with COVID-19 in the UK, underscoring the success of this strategy.2, 3 Many countries, both in the early and advanced phases of their vaccination campaigns, are facing new instances of illness with VOCs that have acquired mutations facilitating increased transmission and evasion of pre-existing immunity. These VOCs might cause improved morbidity and mortality.4, 5, 6 The B.1.1.7 (also known as Alpha) VOC has been reported in more than 114 countries, the B.1.351 (also known as Beta) VOC in more than 68 countries, and the P.1 (also known as Gamma) VOC in more than 37 countries, and new instances continue to be reported worldwide. Additional VOCs, such as EC1454 B.1.617.2, are likely to continue to emerge and threaten our EC1454 ongoing COVID-19 vaccination programmes. Early reports in 2021, suggest that both single-dose and two-dose vaccination regimens are showing gaps in safety.7, 8 In South Africa, a two-dose routine of the ChAdOx1 nCoV-19 vaccine did not show safety against mild-to-moderate COVID-19 after illness with the B.1.351 variant.9 Additionally, a report of individuals immunised with BNT162b2 in Qatar found that vaccine effectiveness was 149% lower against the B.1.351 VOC than the B.1.1.7 VOC, and indicated a notable quantity of breakthrough infections.10 Similar concerns were also noted inside a case-cohort study in Israel, which found disproportionately high infection rates with B.1.351 in fully vaccinated compared with unvaccinated individuals.11 These findings suggest that, despite aggressive immunisation programmes, the presence of circulating VOCs symbolize a serious concern for the emergence of vaccine escape variants that are either more transmissable or virulent, or both, than the vaccine strain or are EC1454 able to escape vaccine-induced neutralising antibodies. Understanding the threshold levels of protecting immunity against VOCs in specific risk organizations and in the general human population during ongoing transmission is important for informing and refocusing immunisation strategies. Providing data within the immune correlates of safety in clinically vulnerable groups is needed to inform the development of effective next-generation, variant-resistant vaccines. The UK has more than 35 million people within the Shielded Patient List, which comprises those who are clinically extremely vulnerable and often prone to prolonged infections, including individuals with malignancy and transplant recipients. Shielding individuals possess a greater risk of morbidity and mortality than the general human population, and those with the inability to clear infections, such as Rabbit polyclonal to OAT immunodeficient individuals, might EC1454 themselves amplify fresh viral variants.12 We did a single-centre, cross-sectional study of immunodeficient outpatients and health-care workers employed at the same tertiary critical care National Health Services (NHS) Trust to understand the spectrum of immunity to the B.1 vaccine strain compared with three major VOCs after vaccination with one dose of either BNT162b2 or ChAdOx1 nCoV-19. To establish the current level of immunity to VOCs in a healthy human population, we compared NAbs induced by either BNT162b2 or ChAdOx1 nCoV-19 in 142 vaccinated health-care workers. In addition, we screened 107 outpatients with a range of immunodeficiencies for the presence of SARS-CoV-2 binding antibodies. This group included individuals with both main and EC1454 secondary immunodeficiencies, such as common variable immunodeficiency syndrome and specific polysaccharide antibody deficiency syndrome. We assessed the ability of serum antibodies from vaccinated health-care workers and immunodeficient outpatients to neutralise the B.1 vaccine strain, as well as the three VOCs, B.1.1.7, B.1.351, and P.1. We used a validated SARS-CoV-2 pseudovirus neutralisation assay standardised against WHO research standards (the National Institute for Biological Requirements and Control) to calculate NAb titres.13 Our results revealed either undetectable antibodies or low NAb titres in immunodeficient outpatients, with only four (5%) of 80 showing detectable neutralisation of B.1.1.7 and two (3%) showing detectable neutralisation of B.1.351 (appendix). Although several vaccinated health-care workers without earlier SARS-CoV-2 exposure showed a range of NAb titres, these titres were markedly lower than in health-care workers with earlier SARS-CoV-2 exposure (appendix). Of the health-care workers without earlier SARS-CoV-2 exposure,.