Gabriela Alvarado
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Hepatitis Viruses Studies and Epidemiology
- Respiratory viral infections research
- SARS-CoV-2 detection and testing
- Viral Infections and Immunology Research
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- COVID-19 Clinical Research Studies
- Bacteriophages and microbial interactions
- Genetic and Kidney Cyst Diseases
- Cardiovascular Health and Disease Prevention
- Barrier Structure and Function Studies
- Ocular Diseases and Behçet’s Syndrome
- Cytomegalovirus and herpesvirus research
- Cystic Fibrosis Research Advances
- Retinal Imaging and Analysis
- Inflammatory Bowel Disease
- Pneumonia and Respiratory Infections
- Cellular transport and secretion
- Cerebrovascular and Carotid Artery Diseases
- RNA and protein synthesis mechanisms
- Microtubule and mitosis dynamics
- Intensive Care Unit Cognitive Disorders
Centro Universitario de Occidente
2022-2024
Vanderbilt University Medical Center
2016-2022
National Institutes of Health
2020-2021
National Institute of Allergy and Infectious Diseases
2020-2021
Vanderbilt University
2015-2018
University of Miami
2009-2014
Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important evaluate nonhuman primates. Nonhuman primates received 10 or 100 μg mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein SARS-CoV-2, no vaccine. Antibody T-cell responses were assessed before upper- lower-airway challenge with SARS-CoV-2. Active genomes...
Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no or doses ranging from 0.3 to 100 μg the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced bronchoalveolar lavages nasal swabs after SARS-CoV-2 challenge vaccinated animals most strongly...
A look at variant-specific boosters The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants concern (VOCs) has raised the question whether current COVID-19 vaccines protect against VOCs and if a variant specific vaccine may be needed. Of currently identified VOCs, Delta is believed to most transmissible, whereas Beta appears resistant. Corbett et al . looked effect boosting using either original WA-1 strain or variant–specific booster. Around 6 months after...
Abstract Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model SARS-CoV-2 infection replicates key features human and may to define immune following vaccination. Here, NHP received either no or doses ranging from 0.3 – 100 μg mRNA-1273, a mRNA encoding the prefusion-stabilized spike (S-2P) protein encapsulated in lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating mucosal antibody responses dose-dependent...
Abstract The rational development of norovirus vaccine candidates requires a deep understanding the antigenic diversity and mechanisms neutralization virus. Here, we isolate characterize panel broadly cross-reactive naturally occurring human monoclonal IgMs, IgAs IgGs reactive with (HuNoV) genogroup I or II (GI GII). We note three binding patterns identify antibodies (mAbs) that neutralize at least one GI GII HuNoV strain when using histo-blood group antigen (HBGA) blocking assay. HBGA assay...
Rab11a is a key component of the apical recycling endosome that aids in trafficking proteins to luminal surface polarized epithelial cells. Utilizing conditional intestinal cell-specific knockout mice and human colonic CaCo2-BBE cells with stable knockdown, we examined molecular pathological impact deficiency on establishment cell polarity microvillus morphogenesis. We demonstrate loss induced alterations enterocyte polarity, shortened microvillar length formation microvilli along lateral...
Human noroviruses (HuNoVs) cause sporadic and epidemic gastroenteritis worldwide. They are classified into two major genogroups (GI GII), with each genogroup further divided multiple genotypes. Susceptibility to these viruses is influenced by genetically determined histo-blood group antigen (HBGA) expression. HBGAs function as cell attachment factors binding a surface-exposed region in the protruding (P) domain of capsid protein. Sequence variations this that result differential HBGA...
Significance Respiratory syncytial virus is a highly contagious human pathogen, infecting the majority of infants before age 2 y, and leading cause viral bronchiolitis pneumonia in children. An approved prophylactic humanized mouse monoclonal antibody, palivizumab, currently standard-of-care treatment for immunocompromised individuals, competition with palivizumab has been proposed as basis measuring effective immune responses vaccine trials. Using combination X-ray crystallography,...
Respiratory syncytial virus (RSV) is a major human pathogen that infects the majority of children by two years age. The RSV fusion (F) protein primary target antibodies, and it has several antigenic regions capable inducing neutralizing antibodies. Antigenic site IV preserved in both pre-fusion post-fusion conformations F. Antibodies to have been described bind neutralize metapneumovirus (hMPV). To explore diversity binding modes at IV, we generated panel four new monoclonal antibodies...
Mutation in the tubby gene causes adult-onset obesity, progressive retinal, and cochlear degeneration with unknown mechanism. In contrast, mutations tubby-like protein 1 (Tulp1), whose C-terminus is highly homologous to tubby, only lead retinal degeneration. We speculate that their diverse N-terminus may define distinct disease profile. To elucidate binding partners of we used (tubby-N) as bait identify proteins open-reading-frame (ORF) phage display. T7 display was engineered three...
Noroviruses (NoV) are the most common cause of non-bacterial acute gastroenteritis and local outbreaks illness, especially in confined situations. Despite being identified four decades ago, correlates protection against norovirus still elucidated. Recent studies have shown an association with NoV-specific serum histo-blood group antigen-blocking antibody IgA patients vaccinated NoV VLPs. Here, we describe isolation characterization human monoclonal IgG antibodies a GI.I NoV, Norwalk virus...
Human noroviruses are the major viral cause of acute gastroenteritis around world. Although norovirus symptoms in most cases mild and self-limited, severe prolonged can occur elderly immunocompromised individuals. Thus, there is a great need for development specific therapeutics that help mitigate infection. In this study, we sought to characterize panel human monoclonal antibodies (mAbs; NORO-123, -115, -273A, -263, -315B, -250B) showed carbohydrate blocking activity against current...
Abstract Intestinal epithelial cells form a physical barrier that is tightly regulated to control intestinal permeability. Proinflammatory cytokines, such as TNF-α, increase permeability through disruption of junctions. The regulation the in inflammatory gastrointestinal disease remains be fully characterized. In this article, we show human bowel genetic susceptibility gene C1ORF106 plays key role regulating gut directly interacts with cytohesins maintain functional cell C1orf106-deficient...
Vaccine efficacy against the B.1.351 variant following mRNA-1273 vaccination in humans has not been determined. Nonhuman primates (NHP) are a useful model for demonstrating whether mediates protection B.1.351. received 30 or 100 µg of as prime-boost vaccine at 0 and 4 weeks, single immunization week 0, no vaccine. Antibody T cell responses were assessed blood, bronchioalveolar lavages (BAL), nasal washes. Viral replication BAL swabs determined by qRT-PCR sgRNA, histopathology viral antigen...
Neutralizing antibody responses gradually wane after vaccination with mRNA-1273 against several variants of concern (VOC), and additional boost vaccinations may be required to sustain immunity protection. Here, we evaluated the immune in nonhuman primates that received 100 µg vaccine at 0 4 weeks were boosted week 29 (homologous) or mRNA-1273.β (heterologous), which encompasses spike sequence B.1.351 (beta β) variant. Reciprocal ID 50 pseudovirus neutralizing geometric mean titers (GMT) live...