Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity.

Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.

Virtual insulin pump initiation is safe effective in children adolescents with type 1 diabetes.

Objective: There is no head-to-head comparison of the safety and efficacy of virtual versus in-office insulin pump initiation for youth with type 1 diabetes in the US. The study's aim was to determine the safety and efficacy of virtual versus in-office pump initiation in pediatric type 1 diabetes. Research design and methods: A longitudinal retrospective study of 112 subjects: 65% (n=73), ages 11.2 ± 3.8 years(y), received in-office training; and 35% (n=39), ages 12.0 ± 4.0y, received virtual training. The number of White subjects was 40 (55%) in the in-office group, and 25 (66%) in the remote group; while Black subjects were 11 (15%) in the in-office group and 4 (10%) in the virtual group. Data were collected at pump initiation, 3 and 6 months. Results: There were no significant differences in sex, race, height, weight, BMI, and the duration of diabetes between the groups at baseline. There was no significant difference in A1c between the groups at 0, 3, and 6 months. A1c correlated significantly with the glucose management indicator at 0, 3, and 6 months: baseline: r=0.49, p<0.0001; 3 months: r=0.77, p<0.0001; and 6 months: r=0.71, p<0.0001. There was no relationship between A1c or TIR and pubertal status, BMI, sex, or race. A1c was significantly elevated in the non-White individuals at 6 months only: 57.9 mmol/mol (50.8-69.4) versus 51.9 mmol/mol (46.5-59.6)], p=0.007. Conclusion: Virtual insulin pump initiation is safe and effective in children with type 1 diabetes. This approach could accelerate the adoption of the use of diabetes technology in minority populations in the US.

Repertoires of SARS-CoV-2 epitopes targeted by antibodies vary according to severity of COVID-19.

Antibodies to SARS-CoV-2 are central to recovery and immunity from COVID-19. However, the relationship between disease severity and the repertoire of antibodies against specific SARS-CoV-2 epitopes an individual develops following exposure remains incompletely understood. Here, we studied seroprevalence of antibodies to specific SARS-CoV-2 and other betacoronavirus antigens in a well-annotated, community sample of convalescent and never-infected individuals obtained in August 2020. One hundred and twenty-four participants were classified into five groups: previously exposed but without evidence of infection, having no known exposure or evidence of infection, seroconverted without symptoms, previously diagnosed with symptomatic COVID-19, and recovered after hospitalization with COVID-19. Prevalence of IgGs specific to the following antigens was compared between the five groups: recombinant SARS-CoV-2 and betacoronavirus spike and nucleocapsid protein domains, peptides from a tiled array of 22-mers corresponding to the entire spike and nucleocapsid proteins, and peptides corresponding to predicted immunogenic regions from other proteins of SARS-CoV-2. Antibody abundance generally correlated positively with severity of prior illness. A number of specific immunogenic peptides and some that may be associated with milder illness or protection from symptomatic infection were identified. No convincing association was observed between antibodies to Receptor Binding Domain(s) (RBDs) of less pathogenic betacoronaviruses HKU1 or OC43 and COVID-19 severity. However, apparent cross-reaction with SARS-CoV RBD was evident and some predominantly asymptomatic individuals had antibodies to both MERS-CoV and SARS-CoV RBDs. Findings from this pilot study may inform development of diagnostics, vaccines, and therapeutic antibodies, and provide insight into viral pathogenic mechanisms.

Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity.

Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Crossneutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.