Biology subjects

Gazi, M.

Publications and source records attributed to Gazi, M..

7 recordsLinked to original sources

bioRxiv2025

Single dose alum adjuvanted RBD protein vaccine provides protection against homologous challenge with SARS-CoV-2 Washington strain and heterologous rechallenge with Delta and Omicron BA.5 variants in K18 hACE2 mouse model

Most COVID-19 vaccination strategies require at least two doses-a primary vaccine followed by a booster dose with the updated variant-specific vaccine. However, vaccine and booster dose hesitancy make it challenging to administer multiple doses of vaccines in the unvaccinated and vaccinated populations, respectively. Thus, it is important to determine if vaccinated individuals exposed to SARS-CoV-2 infection develop immune responses that may protect them against emerging variants of concern (VoCs). We have developed mouse models to understand the protective efficacy of an RBD-based vaccine against challenge and rechallenge with SARS-CoV-2 VoCs. Mice were vaccinated with RBD protein vaccine formulated in 2% Alhydrogel (alum) adjuvant by subcutaneous route. To determine the efficacy of RBD vaccine, mice were challenged approximately 4 weeks post-vaccination with SARS-CoV-2 variants by intranasal route. To determine the efficacy of RBD vaccine against SARS-CoV-2 rechallenge, mice were rechallenged with SARS-CoV-2 Delta and Omicron BA.5 variants at day 14 post SARS-CoV-2 Washington (WA) strain challenge. Our data suggest that single dose alum adjuvanted RBD protein from Wuhan strain provides protection against homologous challenge with SARS-CoV-2 WA strain but failed to provide protection against heterologous challenge with Delta and Omicron BA.5 variants. Interestingly, vaccinated mice that survived homologous challenge with the WA strain showed protection against heterologous rechallenge with Delta and omicron BA.5 variants. Furthermore, infectious viral loads of Delta and Omicron BA.5 were not detected in the lung tissues collected from the rechallenged mice at 3 days post-rechallenge. The data suggest that a single dose RBD vaccine from the ancestral Wuhan strain together with survival from WA strain challenge induces protective immune responses against Delta and Omicron BA.5 variants rechallenge. These mouse models will be useful to determine the immune responses that correlate with protection against challenge and rechallenge with SARS-CoV-2 VoCs.

microbiology↗

bioRxiv2025

Potent neutralization of Marburg virus by a vaccine-elicited monoclonal antibody

Marburg virus (MARV) is a filovirus that causes a severe and often lethal hemorrhagic fever. Despite the increasing frequency of MARV outbreaks, no vaccines or therapeutics are licensed for use in humans. Here, we designed mutations that improve the expression and thermostability of the prefusion MARV glycoprotein (GP) ectodomain trimer, which is the sole target of neutralizing antibodies and vaccines in development. We discovered a fully human monoclonal antibody, MARV16, that broadly neutralizes all MARV isolates as well as Ravn virus and Dehong virus with 40 to 100-fold increased potency relative to previously described antibodies. We determined a cryo-electron microscopy structure of MARV16-bound MARV GP showing that MARV16 recognizes a prefusion-specific epitope spanning GP1 and GP2, blocking receptor binding and preventing conformational changes required for viral entry. We further reveal the architecture of the MARV GP glycan cap, which shields the receptor binding site (RBS), underscoring architectural similarities with distantly related filovirus GPs. MARV16 and previously identified RBS-directed antibodies can bind MARV GP simultaneously, paving the way for a MARV therapeutic antibody cocktail. MARV GP stabilization along with the discovery of a potent neutralizing antibody will advance treatment and prevention options for MARV.

immunology↗

bioRxiv2022

Development of a Well-Characterized Cynomolgus Macaque Model of Sudan Virus Disease for Support of Product Development

The primary objective of this study was to characterize the disease course in cynomolgus macaques exposed to Sudan virus (SUDV), to determine if infection in this species is an appropriate model for the evaluation of filovirus countermeasures under the FDA Animal Rule. Sudan virus causes Sudan virus disease (SVD), with an average case fatality rate of approximately 50%, and while research is ongoing, presently there are no approved SUDV vaccines or therapies. Well characterized animal models are crucial for further developing and evaluating countermeasures for SUDV. Twenty (20) cynomolgus macaques were exposed intramuscularly to either SUDV or sterile phosphate buffered saline; 10 SUDV-exposed animals were euthanized on schedule to characterize pathology at defined durations post-exposure and 8 SUDV-exposed animals were not part of the scheduled euthanasia cohort. Survival was assessed, along with clinical observations, body weights, body temperatures, hematology, clinical chemistry, coagulation, viral load (serum and tissues), macroscopic observations, and histopathology. There were statistically significant differences between SUDV-exposed animals and mock-exposed animals for 26 parameters, including telemetry body temperature, clinical chemistry parameters, hematology parameters, activated partial thromboplastin time, serum viremia, and biomarkers that characterize the disease course of SUDV in cynomolgus macaques.

microbiology↗

bioRxiv2020

Dynamics of the COVID -19 Related Publications

BackgroundThis study aims to analyze the dynamics of the published articles and preprints of Covid-19 related literature from different scientific databases and sharing platforms. MethodsThe PubMed, Elsevier, and Research Gate (RG) databases were under consideration in this study over a specific time. Analyses were carried out on the number of publications as (a) function of time (day), (b) journals and (c) authors. Doubling time of the number of publications was analyzed for PubMed "all articles" and Elsevier published articles. Analyzed databases were (1A) PubMed "all articles" (01/12/2019-12/06/2020) (1B) PubMed Review articles (01/12/2019-2/5/2020) and (1C) PubMed Clinical Trials (01/01/2020-30/06/2020) (2) Elsevier all publications (01/12/2019-25/05/2020) (3) RG (Article, Pre Print, Technical Report) (15/04/2020-30/4/2020). FindingsTotal publications in the observation period for PubMed, Elsevier, and RG were 23000, 5898 and 5393 respectively. The average number of publications/day for PubMed, Elsevier and RG were 70.0 {+/-}128.6, 77.6{+/-}125.3 and 255.6{+/-}205.8 respectively. PubMed shows an avalanche in the number of publication around May 10, number of publications jumped from 6.0{+/-}8.4/day to 282.5{+/-}110.3/day. The average doubling time for PubMed, Elsevier, and RG was 10.3{+/-}4 days, 20.6 days, and 2.3{+/-}2.0 days respectively. In PubMed average articles/journal was 5.2{+/-}10.3 and top 20 authors representing 935 articles are of Chinese descent. The average number of publications per author for PubMed, Elsevier, and RG was 1.2{+/-}1.4, 1.3{+/-}0.9, and 1.1{+/-}0.4 respectively. Subgroup analysis, PubMed review articles mean and median review time for each article were <0|17{+/-}17|77> and 13.9 days respectively; and reducing at a rate of-0.21 days (count)/day. InterpretationAlthough the disease has been known for around 6 months, the number of publications related to the Covid-19 until now is huge and growing very fast with time. It is essential to rationalize the publications scientifically by the researchers, authors, reviewers, and publishing houses. FundingNone

scientific communication and education↗

bioRxiv2020

REGN-COV2 antibody cocktail prevents and treats SARS-CoV-2 infection in rhesus macaques and hamsters

An urgent global quest for effective therapies to prevent and treat COVID-19 disease is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987+REGN10933) targeting non-overlapping epitopes on the SARS-CoV-2 spike protein. In this report, we evaluate the in vivo efficacy of this antibody cocktail in both rhesus macaques and golden hamsters and demonstrate that REGN-COV-2 can greatly reduce virus load in lower and upper airway and decrease virus induced pathological sequalae when administered prophylactically or therapeutically. Our results provide evidence of the therapeutic potential of this antibody cocktail.

microbiology↗

bioRxiv2020

Lethality of SARS-CoV-2 infection in K18 human angiotensin converting enzyme 2 transgenic mice

ABSTRACTVaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease currently lacks a validated small animal model. Here, we show that transgenic mice expressing human angiotensin converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2-transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2-transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 4. K18 hACE2-transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.

microbiology↗

bioRxiv2020

SARS-CoV-2 infection leads to acute infection with dynamic cellular and inflammatory flux in the lung that varies across nonhuman primate species

There are no known cures or vaccines for COVID-19, the defining pandemic of this era. Animal models are essential to fast track new interventions and nonhuman primate (NHP) models of other infectious diseases have proven extremely valuable. Here we compare SARS-CoV-2 infection in three species of experimentally infected NHPs (rhesus macaques, baboons, and marmosets). During the first 3 days, macaques developed clinical signatures of viral infection and systemic inflammation, coupled with early evidence of viral replication and mild-to-moderate interstitial and alveolar pneumonitis, as well as extra-pulmonary pathologies. Cone-beam CT scans showed evidence of moderate pneumonia, which progressed over 3 days. Longitudinal studies showed that while both young and old macaques developed early signs of COVID-19, both groups recovered within a two-week period. Recovery was characterized by low-levels of viral persistence in the lung, suggesting mechanisms by which individuals with compromised immune systems may be susceptible to prolonged and progressive COVID-19. The lung compartment contained a complex early inflammatory milieu with an influx of innate and adaptive immune cells, particularly interstitial macrophages, neutrophils and plasmacytoid dendritic cells, and a prominent Type I-interferon response. While macaques developed moderate disease, baboons exhibited prolonged shedding of virus and extensive pathology following infection; and marmosets demonstrated a milder form of infection. These results showcase in critical detail, the robust early cellular immune responses to SARS-CoV-2 infection, which are not sterilizing and likely impact development of antibody responses. Thus, various NHP genera recapitulate heterogeneous progression of COVID-19. Rhesus macaques and baboons develop different, quantifiable disease attributes making them immediately available essential models to test new vaccines and therapies.

immunology↗