There is an urgent need to generate effective vaccine against #SARSCoV2. This is such an important topic, and many agencies/labs/companies are working on it. I want to open up this discussion here. Let's unite towards this goal.
Pls RT, chime in with your insights/thoughts.
1/n
Learning from previous #CoV studies, what is likely to be the correlate of protection? What vaccine approaches generate best neutralizing antibody (Ab)? How quickly does #CoV generally mutate away from Ab-mediated recognition?
2/n
What would be a good preclinical model to test vaccine efficacy against #CoV? How well do antibodies to previous #CoVs cross-react against other members including #SARSCoV1, #MERSCoV and #SARSCoV2?
3/n
BTW, if you are interested in doing research on #SARSCoV2 vaccines, pathogenesis and related topics, @NIAIDFunding released this last week 👇🏽
@NIAIDFunding I just read this timely and useful summary of various companies and academic labs developing #COVID19 vaccines in @BioCentury. Adding this to my thread.
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/)
An important study by F. Eun-Hyung Lee's team shows that long lived plasma cells (the source of long-term circulating antibodies) fail to establish after mRNA vaccination (even combined with SARS-CoV-2 infection). 🧵 (1/) nature.com/articles/s4159…
The longevity of antibody-mediated protection against infectious diseases rely on whether or not the vaccines can establish long lived plasma cells (LLPC) in the bone marrow. They are the source of circulating antibodies for years to decades. (2/) nature.com/articles/s4159…
The study by Nguyen et al examined the long lived and short lived plasma cells in the bone marrow in people who received COVID mRNA vaccines, tetanus and flu vaccines at various time points . They found no LLPC (PopD) specific to COVID but found PopD against tetanus and flu. (3/)