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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes a tremendous threat to global health. Although vaccines against the virus are under development, the antigen epitopes on the virus and their immunogenicity are poorly understood. Here, we simulated the three-dimensional structures of SARS-CoV-2 proteins with high performance computer, predicted the B cell epitopes on spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches, and then validated the epitope immunogenicity by immunizing mice. Almost all 33 predicted epitopes effectively induced antibody production, six of which were immunodominant epitopes in patients identified via the binding of epitopes with the sera from domestic and imported COVID-19 patients, and 23 were conserved within SARS-CoV-2, SARS-CoV and bat coronavirus RaTG13. We also found that the immunodominant epitopes of domestic SARS-CoV-2 were different from that of the imported, which may be caused by the mutations on S (G614D) and N proteins. Importantly, we validated that eight epitopes on S protein elicited neutralizing antibodies that blocked the cell entry of both D614 and G614 pseudo-virus of SARS-CoV-2, three and nine epitopes induced D614 or G614 neutralizing antibodies, respectively. Our present study shed light on the immunodominance, neutralization, and conserved epitopes on SARS-CoV-2 which are potently used for the diagnosis, virus classification and the vaccine design tackling inefficiency, virus mutation and different species of coronaviruses.
RESUMO
<p><b>BACKGROUND</b>Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is the most frequent type of non-Hodgkin's lymphoma (NHL) that primarily involves the lungs. It represents a rare entity accounting for less than 1% of all NHLs and the clinical features have yet to be clearly elucidated.</p><p><b>METHODS</b>The clinicopathological features and radiological data of 23 patients with pulmonary MALT lymphoma confirmed by biopsy in Peking Union Medical College Hospital from January 2001 to December 2010 were retrospectively analyzed.</p><p><b>RESULTS</b>At diagnosis, there were 15 women and 8 men. The median age was 55.1 years (range, 37 - 73 years). One patient had a history of primary Sjoren's syndrome, another patient had a history of systemic lupus erythematosus (SLE) and secondary Sjoren's syndrome. One patient had a history of previous hematological malignancy (lymphomatoid papulosis in complete remission). In addition, one patient had simultaneous gastric and pulmonary involvement and one patient had simultaneous parotid gland and pulmonary involvement. The other 21 patients had disease localized within the lungs at the initial diagnosis. Among them, 10 patients were asymptomatic while two had non-specific pulmonary symptoms. There were six patients with fever, four patients had low grade fever and two patients had moderate-high fever. The most common manifestations were cough (n = 10), expectoration (n = 8), exertional dyspnea (n = 8), fatigue (n = 7), body weight loss (n = 6) and crackles (n = 6). Blood tests showed low to moderate anemia in six cases, elevated erythrocyte semimentation rate (ESR) in 10 cases and only one patient had elevated lactate dehydrogenase (LDH). High resolution computed tomography (HRCT) of the chest revealed bilateral disease in 13 patients, air space consolidation with or without air bronchogram in 15 patients, lung nodules in 15 patients, patchy opacities in eight patients, lung mass in three patients and pleural effusion in five patients. Flexible fiberoptic bronchoscopy showed multiple nodules in five patients and almost normal morphology in 18 patients. Pathological diagnosis was obtained by bronchial biopsies in three cases, by CT-guided percutaneous lung biopsies in 11 cases and by surgical biopsies in nine cases. Of the 23 patients, one remained untreated, while 22 received various combinations of treatment (surgery alone in three patients, surgery plus chemotherapy in six patients, and chemotherapy alone in 13 patients). Twenty-one patients remained alive during the median follow-up of 23 (0.25 - 84) months, while one patient died from unknown causes, one patient died from lung infection.</p><p><b>CONCLUSIONS</b>Pulmonary MALT lymphoma tends to occur in old-aged females and to be limited to the lungs on the initial diagnosis and LDH's level was normal in most patients. Lung nodules, patchy opacities and air space consolidation were the main HRCT manifestations. Association with immunohistochemical studies, CT-guided percutaneous lung biopsies and surgical biopsies were helpful to the diagnosis. Prognosis for this lymphoma tends to be indolent.</p>
