The SARS-CoV-2 Antibodies, Their Diagnostic Utility, and Their Potential for Vaccine Development.

Antibodies (Abs) are important immune mediators and powerful diagnostic markers in a wide range of infectious diseases. Understanding the humoral immunity or the development of effective antibodies against SARS-CoV-2 is a prerequisite for limiting disease burden in the community and aids in the development of new diagnostic, therapeutic, and vaccination options. Accordingly, the role of antiviral antibodies in the resistance to and diagnosis of SARS-CoV-2 infection was explored. Antibody testing showed the potential in adding important diagnostic value to the routine diagnosis and clinical management of COVID-19. They could also play a critical role in COVID-19 surveillance, allowing for a better understanding of the full scope of the disease. The development of several vaccines and the success of passive immunotherapy suggest that anti-SARS-CoV-2 antibodies have the potential to be used in the treatment and prevention of SARS-CoV-2 infection. In this review, we highlight the role of antibodies in the diagnosis of SARS-CoV-2 infection and provide an update on their protective roles in controlling SARS-CoV-2 infection as well as vaccine development.

Immunomodulatory Effects of Asiaticoside Against Shigella flexneri-Infected Macrophages.

Macrophages provide the first line of defense against Shigella flexneri infection in the gastrointestinal tract by inducing a variety of inflammatory and antimicrobial responses. Secondary metabolites of plants are used as drugs against infections that are resistant to common antibiotics. In this study, the innate effects of asiaticoside on the proinflammatory activity of mouse macrophages infected with S. flexneri were investigated. The viability of the infected mouse macrophages were examined using viability assay, while the pro-inflammatory cytokines productions were determined using the enzyme-linked immunosorbent assay (ELISA) for determination of IL-1ß, IL-12 p40 and TNF-α levels. The production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) protein were determined using the Griess assay and western blot, respectively. Statistical analyses were performed using the Statistical Package of Social Sciences (SPSS) software, version 20. The data obtained from independent experiments (n = 3) were presented as the mean ± standard error of mean (SEM). The results showed that, asiaticoside stimulated the infected macrophages by stimulating increased production of TNF-α, IL-12 p40 and NO as well as increased expression of iNOS in a dose-dependent manner. In contrast the viability of the cells and the production of IL-1ß and were reduced also in a dose-dependent manner when compared to untreated cells. These results indicate that asiaticoside has immunomodulatory effects on the innate immune function of infected macrophages, showing the potential use of this compound to reduce the clinical symptoms of the infections.

Makrofaj bertindak sebagai sistem pertahanan awal terhadap jangkitan Shigella flexneri di dalam saluran gastrousus (saluran pencernaan) dengan mengaktifkan gerak balas inflamatori dan anti-mikrob. Banyak metabolit sekunder daripada tumbuhan digunakan sebagai agen untuk merawat penyakit yang rintang terhadap antibiotik. Dalam kajian ini, kesan gerak balas semulajadi asiatikosid terhadap aktiviti pro-inflamasi makrofaj mencit yang telah dijangkiti S. flexneri telah dikaji. Kedayahidupan makrofaj mencit dianalisis menggunakan asai kedayahidupan, manakala penghasilan sitokin pro-inflamasi IL-1ß, IL-12 p40 dan TNF-α dianalisis menggunakan esei imunoserapan terangkai enzim (ELISA). Penghasilan nitrik oksida (NO) dan pengekspresian protein sintase niktrik oksida teraruh (iNOS) dianalisis menggunakan asai Griess dan analisis pemblotan Western. Analisis statistik dijalankan menggunakan perisian 'Statistical Package of Social Sciences (SPSS)' versi 20. Data yang diperolehi daripada eksperimen tak bersandar (n = 3) dibentangkan sebagai min ± min ralat piawai (SEM). Hasil kajian menunjukkan, asiatikosid merangsang pengaktifan makrofaj mencit yang telah dijangkiti melalui peningkatan penghasilan TNF-α, IL12 p40 dan NO serta meningkatkan penghasilan iNOS bergantung kepada dos asiatikosid yang diberikan. Namun begitu, kedayahidupan sel dan penghasilan IL-1ß menurun seiring dengan dos yang diberikan dalam sel yang dirawat berbanding dengan sel yang tidak dirawat. Hasil kajian ini menunjukkan bahawa asiatikosid mempunyai kesan imunomodulatori terhadap fungsi imun semulajadi makrofaj yang dijangkiti, yang memberi gambaran potensinya untuk digunakan bagi mengurangkan simptom klinikal jangkitan S. flexneri.

Toxicological studies and bioactivity-guided identification of antimicrobially active compounds from crude aqueous stem bark extract of Boswellia dalzielii.

OBJECTIVE: The main objective of this study is to isolate, identify, and quantify the active antimicrobial compounds present in the crude aqueous stem bark extract of B. dalzielii using some common pathogenic microorganisms as well as toxicological profile. MATERIAL AND METHODS: Crude aqueous stem bark extract of Boswellia dalzielii (CASEB) was partitioned by preparative thin layer chromatography (PTLC) using chloroform-methanol-water, 8:2:1 (v/v). The resulting bands were extracted using chloroform-methanol (50:50). The extract of each band was evaluated for antimicrobial activity on Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Klebsiella pneumonia, Pseudomonas aeruginosa, Proteus mirabilis, Salmonella typhi, and Candida albicans by disc diffusion. Compounds in the most antimicrobially bioactive fraction (MAAF) were identified by high performance liquid chromatography (HPLC), Fourier transform infrared spectrophotometry (FT-IR), and gas chromatography-mass spectrometry (GC-MS). Toxicological profile of the CASEB was evaluated by studying its effect in albino Wister rats. RESULTS: PTLC produced five bands/fractions of which the MAAF was identified as RF2-fraction being active against all the isolates except E. coli and K. pneumoniae. HPLC of the MAAF revealed seven components; FT-IR revealed 17 functional groups; GC-MS revealed five compounds of which 93.18% are Oleic acid (44.88%), Squalene (34.16%), and n-Hexadecanoic acid (14.14%). The acute toxicity showed LD50 > 3,000 mg/kg. Sub-chronic toxicity showed that higher doses of the CASEB caused significant changes in liver function indices and a fatty change with lymphocytic infiltration (sign of acute hepatitis) in the liver tissues, but none of these changes were observed in the kidneys. CONCLUSION: The antimicrobially active compounds in CASEB were Oleic acid, Squalene, and n-Hexadecanoic acid. These can be further purified and used as precursors of new antimicrobial agents for treating infections especially those due to fungi and Pseudomonas spp. that are known to resist wide array of antimicrobial agents. The LD50 of CASEB is >3,000 mg/kg in rats. However, long-term consumption of CASEB is associated with significant liver damage.

The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum.

INTRODUCTION: An earlier constructed recombinant BCG expressing the MSP-1C of Plasmodium falciparum, induced inflammatory responses leading to significant production of nitric oxide (NO) alongside higher expression of the enzyme inducible nitric oxide synthase (iNOS) and significant production of the regulatory cytokine, IL-10, indicating significant immunomodulatory effects of the construct. The mechanism of these responses had not been established but is thought to involve toll-like receptor 4 (TLR-4). METHODOLOGY: The present study was carried out to determine the role of TLR-4 on eliciting the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum leading to the production of NO and IL-10, as well as the expression of iNOS. Six groups of mice (n = 6 per group) were immunised thrice, three weeks apart with intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242, given one hour prior to each immunisation. Peritoneal macrophages were harvested from the mice and cultured for the determination of NO, iNOS and IL-10 via Griess assay, ELISA and Western blot respectively. RESULTS: The results showed significant inhibition of the production of NO and IL-10 and the expression of iNOS in all groups of mice in the presence of TAK-242. CONCLUSIONS: These results presented evidence of the role of TLR-4/rBCG attachment mechanism in modulating the production of NO and IL-10 and the expression of iNOS in response to our rBCG-based malaria vaccine candidate expressing MSP-1C of P. falciparum.