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To investigate serological correlates of protection against SARS-CoV-2 B.1.617.2 (Delta) infection after two vaccinations. We performed a case-control study, where cases were Delta infections after the second vaccine dose and controls were vaccinated, never infected participants, matched by age, gender and region. Sera were tested for anti-SARS-CoV-2 Spike antibody levels (anti-S) and neutralising antibody titres (nAbT), using live virus microneutralisation against Ancestral, Delta and Omicron (BA.1, B.1.1.529). We modelled the decay of anti-S and nAbT for both groups, inferring levels at matched calendar times since the second vaccination. We assessed differences in inferred antibody titres between groups and used conditional logistic regression to explore the relationship between titres and odds of infection. In total, 130 sequence-confirmed Delta cases and 318 controls were included. Anti-S and Ancestral nAbT decayed similarly between groups, but faster in cases for Delta nAbT (p = 0.02) and Omicron nAbT (p = 0.002). At seven days before infection, controls had higher anti-S levels (p < 0.0001) and nAbT (p < 0.0001; all variants) at matched calendar time. A two-fold increase in anti-S levels was associated with a 29% ([95% CI 14–42%]; p = 0.001) reduction in odds of Delta infection. Delta nAbT>40 were associated with reduced odds of Delta infection (89%, [69–96%]; p < 0.0001), with additional benefits for titres >100 (p = 0.009) and >400 (p = 0.007). We have identified correlates of protection against SARS-CoV-2 Delta, with potential implications for vaccine deployment, development, and public health response. • Identifying post-vaccination SARS-CoV-2 correlates of protection remains critical. • Neutralising antibody titres decay faster in Delta infection cases than controls. • Delta neutralising antibody titres above 40 reduce the odds of infection by 89%. • Neutralising antibodies correlate more accurately with protection than anti-S. [ABSTRACT FROM AUTHOR]

Objectives: To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection.Methods: We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models.Results: We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001-0·31) and LV-N Alpha (OR 0·07, CI 0·009-0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03-0·64) and Alpha (0·06, CI 0·008-0·40).Conclusions: Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect.Trial Registration Number: ISRCTN11041050. [ABSTRACT FROM AUTHOR]

Influenza infection imparts an age-related increase in mortality and morbidity. The most effective countermeasure is vaccination; however, vaccines offer modest protection in older adults. To investigate how aging impacts the memory B cell response, we track hemagglutinin-specific B cells by indexed flow sorting and single-cell RNA sequencing (scRNA-seq) in 20 healthy adults that were administered the trivalent influenza vaccine. We demonstrate age-related skewing in the memory B cell compartment 6 weeks after vaccination, with younger adults developing hemagglutinin-specific memory B cells with an FcRL5 + "atypical" phenotype, showing evidence of somatic hypermutation and positive selection, which happened to a lesser extent in older persons. We use publicly available scRNA-seq from paired human lymph node and blood samples to corroborate that FcRL5 + atypical memory B cells can derive from germinal center (GC) precursors. Together, this study shows that the aged human GC reaction and memory B cell response following vaccination is defective. [Display omitted] • Heterogeneous HA-specific memory B cells expand post influenza vaccination • Older people have reduced expansion of HA+FcRL5+ B cells post immunization • HA+FcRL5+ B cells show evidence of germinal center selection • Positive selection of HA+FcRL5+ B cells is reduced in older individuals Immune responses to vaccination wane with age. Burton et al. used single-cell RNA sequencing and flow cytometry of influenza-vaccine-specific B cells to delineate changes in B cell memory generation, antibody mutation, and their subsequent selection in older persons. [ABSTRACT FROM AUTHOR]

Wu et al. report that patients with hematologic malignancies have reduced immunity against SARS-CoV-2 Omicron subvariants and Sotrovimab retains neutralizing capacity against all tested Omicron subvariants. [ABSTRACT FROM AUTHOR]