BacMam virus-based surface display for HCV E2 glycoprotein induces strong cross-neutralizing antibodies and cellular immune responses in vaccinated mice.

BACKGROUND: Despite recent advancements, limitations in the treatment and control of hepatitis C virus (HCV) infection reprioritized the studies for invention of an efficient HCV vaccine to elicit strong neutralizing antibodies (NAbs) and cellular responses. METHODS: Herein, we report molecular construction of a BacMam virus-based surface display for a subtype-1a HCV gpE2 (Bac-CMV-E2-gp64; Bac) that both expressed and displayed gpE2 in mammalian cells and bacouloviral envelope, respectively. RESULTS: Assessments by western blotting, Immunofluorescence and Immunogold-electron microscopy indicated the proper expression and incorporation in insect cell and baculovirus envelope, respectively. Mice immunized in three different prime-boost immunization groups of: Bac/Bac, Bac/Pro (bacoulovirus-derived gpE2) and Bac/DNA (plasmid DNA (pCDNA)-encoding gpE2) developed high levels of IgG and IFN-γ (highest for Bac/Bac group) indicating the induction of both humeral and cellular immune responses. Calculation of the IgG2a/IgG1 and IFN-γ/IL-4 ratios indicated a Th1 polarization of immune responses in the Bac/Bac and Bac/DNA groups but a balanced Th1-Th2 phenotype in the Bac/Pro group. Sera of the mice in the Bac/Bac group provided the highest percentage of cross-NAbs against a subtype-2a HCVcc (JFH1) compared to Bac/Pro and Bac/DNA groups (62% versus 41% and 6%). CONCLUSIONS: Results indicated that BacMam virus-based surface display for gpE2 might act as both subunit and DNA vaccine and offers a promising strategy for development of HCV vaccine for concurrent induction of strong humoral and cellular immune responses.

Neutrophil to lymphocyte ratio and C-reactive protein level as prognostic markers in mild versus severe COVID-19 patients.

AIM: This research aimed to investigate neutrophil-to-lymphocyte ratio (NLR) with C-reactive protein to identify potential clinical predictors and analyze differences among severe and non-severe COVID-19 patients. BACKGROUND: NLR and CRP are established markers that reflect systemic inflammatory, and these parameters alter in patients with novel coronavirus (SARS-CoV-2) pneumonia (COVID-19). METHODS: A population of patients with COVID-19 referred to Loghman Hospital in Tehran was analyzed. The baseline data of laboratory examinations, including NLR and CRP levels, was collected. Pearson analysis was used to assess the independent relationship between the NLR with disease severity and CRP levels. RESULTS: COVID-19 cases comprised 14 (20%) patients with severe disease and 56 (80%) with non-severe infection. The mean values of WBC, NEU, LYM, and NLR of the severe patients were significantly higher than those of the non-severe patients. Forty-six patients (65.7%) had NLR >1, and the remaining patients had NLR <1. Plasma CRP levels were higher in severe cases than in non-severe cases, and this difference was significant. The results showed that NLR was positively correlated with CRP levels (R=0.23) and negatively correlated with WBC (R=-0.38). CRP (AUC = 0.97, 95% CI: 0.95-0.99) and NLR (AUC = 0.87, 95% CI: 0.81-0.93) had very good accuracy in predicting the severity of COVID-19 disease. CONCLUSION: The findings of this study indicated that the integration of NLR and CRP may lead to improved predictions and is recommended as a valuable early marker to assess prognosis and evaluate the severity of clinical symptoms in COVID-19 patients.