Preventing infection is the best way to avoid diseases like #PAIS. A new study from our team @tianyangmao, Jooyoung Kim, @marioph13 et al shows that a generic antibiotic neomycin acts on the host immune system in the👃🏽to trigger antiviral resistance. (1/)🧵 pnas.org/doi/10.1073/pn…
This work is inspired by @SmitaGopinath et al who showed that an antibiotic class called aminoglycosides has an unusual antiviral property. Aminoglycosides including neomycin trigger interferon-stimulated genes through a TLR3-dependent mechanism. (2/) ncbi.nlm.nih.gov/pmc/articles/P…
In our current study, we showed that nasal application of neomycin in mice one day before infection reduces viral load and disease burden after the SARS-COV-2 challenge. @tianyangmao (3/)
Intranasal application of neomycin also protected mice against highly virulent influenza virus infection. @MiyuMoriyama (4/)
We could also treat mice already infected with SARS-CoV-2 with nasal application of neomycin 4 hours later, in a dose-dependent manner. This led to viral load reduction and increased survival. @tianyangmao (5/)
What about transmission? Hamsters trx 1 day earlier with neomycin were protected from catching the virus from an infected hamster in the same cage. Even if they did, their viral load was ⬇️. Thus, neomycin applied in the nose can shield the host from COVID transmission. @marioph13 (6/)
OK, but does this work in humans? Collaborating with @CDelaCruzMed, we ran a small randomized, double-blind, placebo-controlled trial involving healthy human volunteers, who applied OTC Neosporin (containing neomycin) (n=12) or placebo (vaseline) (n=7) twice daily into their noses with cotton swabs. (7/)
More than half of the human volunteers who applied Neosporin into their noses showed robust antiviral gene expression (interferon-stimulated genes) measured by nasal brush, compared to placebo controls. We believe we can ⬆️ efficacy with higher neomycin doses. (8/)
We acknowledge the limitations of the study and propose future improvements we can make. (9/)
In a nutshell, we showed that over-the-counter cheap generic antibiotic neomycin can be repurposed in nasal formulation to prevent & treat infection, block transmission, and reduce disease burden against a wide array of viruses. Since this is a host-directed strategy and virus-agnostic, it holds promise as a prophylactic strategy against any viral threat. (10/)
Here are the amazing people who made this study possible, and we are grateful for all the human volunteers who participated in the pilot trial. We are grateful to the @gatesfoundation for the encouragement and support of this research 🙏🏽 (end)
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Our preprint on post-vaccination syndrome is out. We studied immune signatures and examined spike protein in the blood of people who have developed chronic illnesses after COVID-19 vaccination. (1/) medrxiv.org/content/10.110…
Vaccines have saved countless lives and inspired me to become an immunologist. While generally safe, some people experience adverse effects, including Post-Vaccination Syndrome (PVS). Studying PVS is crucial for improving patient care and enhancing vaccine safety & acceptance. (2/) pubmed.ncbi.nlm.nih.gov/37986769/
Happy to share our latest work by @YYexin et al. on antibody-mediated control of endogenous retroviruses in mice. In the process, we found “natural antibodies” with broad reactivity against enveloped viruses. Here is how “panviral” antibodies work 🧵(1/)
Endogenous retroviruses (ERV) are remnants of genetic invaders that have integrated into our ancestors' genomes over millions of years. ERVs occupy ~8% of the human genome and are under constant host immune surveillance. (2/) nature.com/articles/nrg31… nature.com/articles/nrmic…
This work started over 7 years ago when @YYexin and @rebecca_treger began to examine why ERVs reactivate in certain mouse strains. Through many genetic crosses, we figured out that secreted IgM recruits complement to suppress infectious ERV from emerging. (3/)
This time, we developed a nasal booster vaccine for influenza viruses. In this preprint, @MiyuMoriyama et al. show that nasal boosters with unadjuvanted hemagglutinin protein induce sterilizing immunity in mice against flu. (1/) biorxiv.org/content/10.110…
This work builds on the Prime and Spike vaccine strategy by @tianyangmao @BenIsraelow et al. against COVID where mRNA vaccine followed by nasal booster with recombinant spike protein established local immunity, ⬇️ infection & transmission in rodents. (2/) science.org/doi/10.1126/sc…
For Prime and HA against flu, @MiyuMoriyama tested several different mRNA IM prime and nasal HA booster doses, followed by a homologous influenza virus challenge. Like Prime and Spike, no adjuvant is needed for the nasal booster due to preexisting immunity from Prime. (3/)
Much-needed data on the genetics of #longCOVID in a new preprint by @23andMeResearch - GWAS of #LongCOVID identified 3 loci pointing to immune and thrombo-inflammatory mechanisms 🔥 @ninaadsc 1) HLA-DQA1–HLA-DQB 2) ABO 3) BPTF–KPAN2–C17orf58
(1/) medrxiv.org/content/10.110…
Among research participants who reported acute SARS-CoV2 infection, 64,384 participants reported to have experienced Long COVID and 178,537 participants did not. Their analytical cohort consisted of 54,390 cases and 124,777 controls 👇🏼 (2/)
The top locus was in the HLA-DQA1–HLA-DQB intergenic region. Further analysis showed that HLA alleles HLA-DRB1*11:04, HLA-C*07:01, HLA-B*08:01, and HLA-DQA1*03:01 were significantly associated with #LongCOVID. In other words, crucial genes for T cell target detection! (3/)
Keynote talk by @MichaelPelusoMD. “#LongCovid is not a mystery anymore. Working with patients, I have optimism that we can figure this out.” #YaleCIISymposium
An excellent framework in thinking about the pathogenesis of #LongCovid
@MichaelPelusoMD
Sharing this scoping review on "Post-Acute sequelae of COVID-19 in pediatric patients within the United States" by @ChrisMillerDO - an amazing @YalePediatrics infectious diseases fellow focused on research and treatment of #longcovidkids (1/)
Key findings:
- Most pediatric LC patients were adolescents.
- ♀>♂️
- 80% of pediatric LC patients started with a mild initial infection.
- Asthma, atopy, allergic rhinitis (type 2 immune diseases), and obesity were frequently reported pre-existing conditions. (2/)
The most frequently reported symptoms in #longcovidkids are listed here (3/)