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A safe, effective, and scalable vaccine is urgently needed to halt the ongoing SARS-CoV-2 pandemic. Here, we describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 copies of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) in a highly immunogenic array and induce neutralizing antibody titers roughly ten-fold higher than the prefusion-stabilized S ectodomain trimer despite a more than five-fold lower dose. Antibodies elicited by the nanoparticle immunogens target multiple distinct epitopes on the RBD, suggesting that they may not be easily susceptible to escape mutations, and exhibit a significantly lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the protein components and assembled nanoparticles, especially compared to the SARS-CoV-2 prefusion-stabilized S trimer, suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms for inducing potent neutralizing antibody responses and have launched cGMP manufacturing efforts to advance the lead RBD nanoparticle vaccine into the clinic.
RESUMO
The recently emerged SARS-CoV-2 virus is currently causing a global pandemic and cases continue to rise. The majority of infected individuals experience mildly symptomatic coronavirus disease 2019 (COVID-19), but it is unknown whether this can induce persistent immune memory that might contribute to herd immunity. Thus, we performed a longitudinal assessment of individuals recovered from mildly symptomatic COVID-19 to determine if they develop and sustain immunological memory against the virus. We found that recovered individuals developed SARS-CoV-2-specific IgG antibody and neutralizing plasma, as well as virus-specific memory B and T cells that not only persisted, but in some cases increased numerically over three months following symptom onset. Furthermore, the SARS-CoV-2-specific memory lymphocytes exhibited characteristics associated with potent antiviral immunity: memory T cells secreted IFN-{gamma} and expanded upon antigen re-encounter, while memory B cells expressed receptors capable of neutralizing virus when expressed as antibodies. These findings demonstrate that mild COVID-19 elicits memory lymphocytes that persist and display functional hallmarks associated with antiviral protective immunity.
RESUMO
BACKGROUND: Liver biopsy is gold standard for fibrosis assessment in hepatitis C virus (HCV) infection but its limitations led to the identification of non-invasive biomarkers. This study assesses the reliability of five biomarkers in estimating the stage of liver fibrosis/cirrhosis in chronic HCV patients versus METAVIR scoring. METHODS: One hundred HCV monoinfected patients who underwent liver biopsy and blood sampling were included. Liver fibrosis was staged (F0-4) and required laboratory tests were performed. AAR, API, APRI, FIB-4 and Pohl score were calculated and their receiver operating curves (ROCs), sensitivities, specificities, predictive values and accuracies were evaluated. RESULTS: There were 27, 44, and 29 patients at F0-F1, F2-F3, and F4 groups. Significant statistical differences were found regarding AST, vireamia, platelet count, prothrombin time and all biomarkers. From ROCs only Pohl score predicted significant fibrosis and cirrhosis but with low accuracy. AAR, API and APRI showed moderate performance at low cut-offs, but had limited predictive values or accuracies at higher cut-offs. FIB-4 was the least accurate test. The diagnostic reliability of these biomarkers was limited to patients with suspected insignificant fibrosis. CONCLUSIONS: This study verified the limited reliability for AAR, API, APRI, FIB-4 and Pohl score in estimating the stage of hepatic fibrosis in HCV infected patients opposed to METAVIR scoring.