Human Antibodies Targeting Influenza B Virus Neuraminidase Active Site Are Broadly Protective.

Influenza B virus (IBV) infections can cause severe disease in children and the elderly. Commonly used antivirals have lower clinical effectiveness against IBV compared to influenza A viruses (IAV). Neuraminidase (NA), the second major surface protein on the influenza virus, is emerging as a target of broadly protective antibodies that recognize the NA active site of IAVs. However, similarly broadly protective antibodies against IBV NA have not been identified. Here, we isolated and characterized human monoclonal antibodies (mAbs) that target IBV NA from an IBV-infected patient. Two mAbs displayed broad and potent capacity to inhibit IBV NA enzymatic activity, neutralize the virus in vitro, and protect against lethal IBV infection in mice in prophylactic and therapeutic settings. These mAbs inserted long CDR-H3 loops into the NA active site, engaging residues highly conserved among IBV NAs. These mAbs provide a blueprint for the development of improved vaccines and therapeutics against IBVs.

Human germinal centres engage memory and naive B cells after influenza vaccination.

Influenza viruses remain a major public health threat. Seasonal influenza vaccination in humans primarily stimulates pre-existing memory B cells, which differentiate into a transient wave of circulating antibody-secreting plasmablasts1-3. This recall response contributes to 'original antigenic sin'-the selective increase of antibody species elicited by previous exposures to influenza virus antigens4. It remains unclear whether such vaccination can also induce germinal centre reactions in the draining lymph nodes, where diversification and maturation of recruited B cells can occur5. Here we used ultrasound-guided fine needle aspiration to serially sample the draining lymph nodes and investigate the dynamics and specificity of germinal centre B cell responses after influenza vaccination in humans. Germinal centre B cells that bind to influenza vaccine could be detected as early as one week after vaccination. In three out of eight participants, we detected vaccine-binding germinal centre B cells up to nine weeks after vaccination. Between 12% and 88% of the responding germinal centre B cell clones overlapped with B cells detected among early circulating plasmablasts. These shared B cell clones had high frequencies of somatic hypermutation and encoded broadly cross-reactive monoclonal antibodies. By contrast, vaccine-induced B cell clones detected only in the germinal centre compartment exhibited significantly lower frequencies of somatic hypermutation and predominantly encoded strain-specific monoclonal antibodies, which suggests a naive B cell origin. Some of these strain-specific monoclonal antibodies recognized epitopes that were not targeted by the early plasmablast response. Thus, influenza virus vaccination in humans can elicit a germinal centre reaction that recruits B cell clones that can target new epitopes, thereby broadening the spectrum of vaccine-induced protective antibodies.

Solitary metastasis to the head of the pancreas from lung adenocarcinoma mimicking pancreatic ductal adenocarcinoma: A case report.

Solitary pancreatic metastasis is a rare cause of pancreatic neoplasm. Pancreatic ductal adenocarcinoma is the primary differential consideration when a solitary pancreatic mass is diagnosed, as it is the most common solitary solid pancreatic neoplasm. A majority of pancreatic ductal adenocarcinomas arise in the region of the head of the pancreas; however, specific neoplastic and non-neoplastic lesions can occur at or adjacent to the pancreatic head, which can mimic a pancreatic ductal adenocarcinoma. Therefore, a histopathological diagnosis is essential for confirming pancreatic ductal adenocarcinoma. Isolated solitary metastasis from primary lung adenocarcinoma is a rare cause of a solitary pancreatic head mass. We report a case in which imaging and pathology were integral to the diagnosis of a solitary lung adenocarcinoma metastasis to the head of the pancreas, which ultimately guided appropriate patient management.

SARS-CoV-2 anti-N antibodies among healthcare personnel without previous known COVID-19.

Objective: To measure SARS-CoV-2 anti-nucleocapsid (anti-N) antibody seropositivity among healthcare personnel (HCP) without a history of COVID-19 and to identify HCP characteristics associated with seropositivity. Design: Prospective cohort study from September 22, 2020, to March 3, 2022. Setting: A tertiary care academic medical center. Participants: 727 HCP without prior positive SARS-CoV-2 PCR testing were enrolled; 559 HCP successfully completed follow-up. Methods: At enrollment and follow-up 1-6 months later, HCP underwent SARS-CoV-2 anti-N testing and were surveyed on demographics, employment information, vaccination status, and COVID-19 symptoms and exposures. Results: Of 727 HCP enrolled, 27 (3.7%) had a positive SARS-CoV-2 anti-N test at enrollment. Seropositive HCPs were more likely to have a household exposure to COVID-19 in the past 30 days (OR 7.92, 95% CI 2.44-25.73), to have had an illness thought to be COVID-19 (4.31, 1.94-9.57), or to work with COVID-19 patients more than half the time (2.09, 0.94-4.77). Among 559 HCP who followed-up, 52 (9.3%) had a positive SARS-CoV-2 anti-N antibody test result. Seropositivity at follow-up was associated with community/household exposures to COVID-19 within the past 30 days (9.50, 5.02-17.96; 2.90, 1.31-6.44), having an illness thought to be COVID-19 (8.24, 4.44-15.29), and working with COVID-19 patients more than half the time (1.50, 0.80-2.78). Conclusions: Among HCP without prior positive SARS-CoV-2 testing, SARS-CoV-2 anti-N seropositivity was comparable to that of the general population and was associated with COVID-19 symptomatology and both occupational and non-occupational exposures to COVID-19.

Association between SARS-CoV-2 Symptoms, Ct Values, and Serological Response in Vaccinated and Unvaccinated Healthcare Personnel.

BACKGROUND: SARS-CoV-2 vaccines are effective at reducing symptomatic and asymptomatic COVID-19. Limited studies have compared symptoms, threshold cycle (Ct) values from reverse transcription (RT)-PCR testing, and serological testing results between previously vaccinated vs unvaccinated populations with SARS-CoV-2 infection. METHODS: Healthcare personnel (HCP) with a positive SARS-CoV-2 RT-PCR test within the previous 14 to 28 days completed surveys including questions about demographics, medical conditions, social factors, and symptoms of COVID-19. Ct values were observed, and serological testing was performed for anti-nucleocapsid (anti-N) and anti-Spike (anti-S) antibodies at enrollment and 40 to 90 days later. Serological results were compared to HCP with no known SARS-CoV-2 infection and negative anti-N testing. RESULTS: There were 104 unvaccinated/not fully vaccinated and 77 vaccinated HCP with 2 doses of an mRNA vaccine at time of infection. No differences in type or duration of symptoms were reported (P = 0.45). The median (interquartile range [IQR]) Ct was 21.4 (17.6-24.6) and 21.5 (18.1-24.6) for the unvaccinated and vaccinated HCP, respectively. Higher anti-N IgG was observed in unvaccinated HCP (5.08 S/CO, 3.08-6.92) than vaccinated (3.61 signal to cutoff ratio [S/CO], 2.16-5.05). Anti-S IgG was highest among vaccinated HCP with infection (34 285 aribitrary units [AU]/mL, 17 672-61 775), followed by vaccinated HCP with no prior infection (1452 AU/mL, 791-2943), then unvaccinated HCP with infection (829 AU/mL, 290-1555). Anti-S IgG decreased 1.56% (0.9%-1.79%) per day in unvaccinated and 0.38% (0.03%-0.94%) in vaccinated HCP. CONCLUSIONS: Vaccinated HCP infected with SARS-CoV-2 reported comparable symptoms and had similar Ct values relative to unvaccinated. However, vaccinated HCP had increased and prolonged anti-S and decreased anti-N response relative to unvaccinated.