SARS-CoV-2 and its variants continue to infect hundreds of thousands every day despite the rollout of effective vaccines. Therefore, it is essential to understand the levels of protection that these vaccines provide in the face of emerging variants. Here, we report two demographically balanced cohorts of BNT162b2 vaccine recipients and COVID-19 patients, from which we evaluate neutralizing antibody titers against SARS-CoV-2 as well as the B.1.1.7 (alpha) and B.1.351 (beta) variants. We show that both B.1.1.7 and B.1.351 are less well neutralized by serum from vaccinated individuals, and that B.1.351, but not B.1.1.7, is less well neutralized by convalescent serum. We also find that the levels of variant-specific anti-spike antibodies are proportional to neutralizing activities. Together, our results demonstrate the escape of the emerging SARS-CoV-2 variants from neutralization by serum antibodies, which may lead to reduced protection from re-infection or increased risk of vaccine breakthrough.

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In the State of Oregon, patients with NTM respiratory isolates have high mortality, regardless of whether they meet ATS/IDSA criteria for pulmonary NTM disease. Most patients die as a result of causes other than NTM infection.

In bronchiectasis, due to diseases other than cystic fibrosis, idiopathic, genetic and environmental factors alter the airway landscape and immune responses, rendering the patients susceptible to infection, with the Gram-negative bacterium (GNB) Pseudomonas aeruginosa as a major contributor to mortality [1, 2]. The high prevalence of P. aeruginosa in bronchiectasis patients cannot be explained by a single genetic or environmental influence, and immunological permissiveness of bronchiectasis airways to this colonisation remains unexplained [2]. A similar predisposition to this pathogen is characteristic of cystic fibrosis patients, in whom a single genetic mutation (CFTR) shapes the abnormal lung environment. In cystic fibrosis, where P. aeruginosa colonises the airways of up to 80% of patients, we and others have proposed that the inability of the innate immune system to combat P. aeruginosa infection is related, in part, to an autoimmune antibody response to bactericidal/permeability-increasing protein (BPI), a neutrophil antimicrobial protein [3]. Through high-affinity binding of lipopolysaccharides (LPS) on the bacterial outer envelope, BPI mediates extracellular bactericidal and LPS neutralising functions [4]. Autoantibodies to BPI were first reported in European cystic fibrosis cohorts and confirmed by us in a US cohort of adult cystic fibrosis patients [5, 6]. Notably, autoreactivity to BPI was associated with diminished lung function while in vitro functional studies demonstrated that anti-BPI IgG inhibits its biological activities [7-9]. In this research letter, we ask two critical questions regarding the immunological interactions that shape the bronchiectatic airway permissiveness to P. aeruginosa infection. 1) Do bronchiectasis patients develop autoimmunity to BPI? 2) What is the relationship between autoreactivity to BPI and chronic infection by P. aeruginosa? To address these questions, autoantibodies to BPI in patient sera were measured by ELISA in two bronchiectasis cohorts from the USA: one from Dartmouth Hitchcock Medical Center (DHMC) in Lebanon, NH (n=16), and the other from Oregon Health and Science University (OHSU) in Portland, OR (n=42). Immunoblotting of sera negative by ELISA yielded a low frequency of additional seropositivity (∼10%). BPI autoreactivity was identified at nearly identical frequencies in the DHMC (56%) and OHSU (52%) cohorts (figure 1a and b). We and others have reported an association between autoreactivity to BPI and the presence of P. aeruginosa in sputum culture of cystic fibrosis patients [5, 6]. Given these findings, we evaluated the relationship between anti-BPI autoimmunity and chronic P. aeruginosa infection in bronchiectasis by measuring anti-P. aeruginosa IgG titres in patient sera as a serological marker of chronic infection. Healthy control sera exhibited little or no reactivity against PA14 extract (figure 1b). Autoreactivity to BPI in the DHMC bronchiectasis cohort was strongly associated with the existence of an antibody response to P. aeruginosa (n=16, p=0...

We tested human sera from large, demographically balanced cohorts of BNT162b2 vaccine recipients (n=51) and COVID-19 patients (n=44) for neutralizing antibodies against SARS-CoV-2 variants B.1.1.7 and B.1.351. Although the effect is more pronounced in the vaccine cohort, both B.1.1.7 and B.1.351 show significantly reduced levels of neutralization by vaccinated and convalescent sera. Age is negatively correlated with neutralization in vaccinee, and levels of variant-specific RBD antibodies are proportional to neutralizing activities.