ABSTRACT
Background: SARS-CoV-2 vaccines capable of inducing broad and cross-reactive humoral and T cell responses help to fight against emerging variants. In this study we compared the immunogenicity and efficacy of modified vaccinia Ankara (MVA) based SARS-CoV-2 vaccine expressing furin-cleavage site inactivated stabilized spike (SdFCS) and nucleocapsid (N) delivered via intramuscular (IM), buccal or sublingual (SL) routes in rhesus macaques (RMs). Methods: Three groups (n=5/group) of RMs were immunized with MVA/SdFCS-N vaccine on weeks 0 and 4, via IM, buccal, or SL route. An additional group (control) received non-recombinant MVA via IM. IM vaccinations were delivered using needle and SL and buccal vaccinations were delivered using a needle-free injection device. All RMs were challenged with B.1.617.2 strain (Delta) of SARS-CoV-2 at week 8 via intratracheal and intranasal routes simultaneously. Various humoral and cellular immune parameters were determined post vaccination and challenge. SARS-CoV-2 subgenomic RNA (sgRNA) was measured to monitor virus replication in the upper (nose) and lower (lung) respiratory tract. Results: IM vaccination induced strong RBD-specific IgG antibody in serum, nose, throat, lung, and rectum. The serum antibody showed strong live virus neutralizing activity against WA-1/2020 (median of 415) and B.1.617.2 strains (median of 317). Serum from IM vaccinated animals also demonstrated strong non-neutralizing effector functions such as ADCD, ADCP and ADNKA. In addition, IM vaccination induced strong CD4 and CD8 T cell response in the blood that was directed against both S and N. In contrast, the SL and buccal vaccination-induced antibody showed lower neutralization titer against WA-1/2020 (143 and 302, respectively), and showed 4.5-fold lower cross reactivity neutralization titer against B.1.617.2 compared to WA-1/2020. Following challenge with B.1.617.2, the IM group RMs showed superior protection with 3 of the 5 animals being negative in upper and lower respiratory airways at Day 2. In contrast, no significant protection was observed in the SL group. Vaccine induced neutralizing and non-neutralizing antibody effector functions showed direct association with protection. Conclusion: Our findings showed that IM vaccination with improved MVA-based SARS-CoV-2 vaccine elicits cross-reactive antibody and T cell responses and protect against heterologous SARS-CoV-2 Delta challenge in RMs. They also showed IM vaccinations are superior to oral vaccinations.
ABSTRACT
Objective: Our study is aimed at defining the epidemiological characteristics and length of stay in the hospitalized SARS-CoV-2 PCR positive patients at UMMC that have Acute Encephalopathy (AE) and related diagnostic synonyms. Background: COVID-19 is a viral illness that is caused by Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2). This was first reported in December 2019, but has spread to many countries affecting nearly 39 million people, causing more than 1 million deaths so far globally. The pandemic has affected more than 100,000 people in Mississippi leading to over 6000 hospitalizations to date. Though the disease has primarily affected the respiratory system, its neurological implications are being increasingly reported. Encephalopathy is the most commonly reported neurological manifestation. Design/Methods: In hospitalized patients who had a positive SARS-CoV-2 PCR test, we used diagnostic codes G93.40 (encephalopathy unspecified), G93.41 (metabolic encephalopathy), G92 (toxic encephalopathy), R41.82 (altered mental status) and R41.0 (delirium/disorientation) to obtain patient data for the study. We have obtained de-identified patient data from EPIC using Patient Cohort Explorer at UMMC till September 30, 2020. Multiple variables were compared. Results: We had a total 1016 patients that were admitted with SARS-CoV-2 PCR test positive and 94 patients had AE and 922 patients did not have AE. The mean age of patients with AE was 64 years (Standard Deviation (SD) of 16) and without AE was 40 years (SD of 23) (p value <0.001). Males had more AE compared to females (53% vs 47%, p value 0.018). AE was more prevalent in Caucasians than African Americans (p value < 0.001). Length of stay was significantly higher in patients with AE (mean of 15 days with SD of 13) compared to 2 days (SD of 5) in non-AE patients (p value <0.001). Conclusions: Length of stay is significantly higher in COVID-19 positive patients with Acute Encephalopathy.