Prof. Akiko Iwasaki Profile picture
We study innate and adaptive immunity to #viruses and #cancer. #COVID19 #immunology #vaccines @HHMINEWS @YaleIBIO @YaleMed @YaleEMD @YaleSPH.
Ross Grayson, MPH, CIH Profile picture phyron Profile picture Perry Ismangil Profile picture Peter English #FBPE Profile picture Bob Adler Profile picture 36 added to My Authors
13 Jan
Top 10 most downloaded articles in 2020 includes our review in the @AnnualReviews Virology - “Seasonality of Respiratory Viral Infections” by @MiyuMoriyama et al! It’s free to download: arevie.ws/3aYt32Y

Here let’s highlight other relevant pieces on the same topic (1/n)
Just to recap, seasonal factors that drive respiratory tract viral infections are mainly these three;

1) ⬇️ Temperature
2) ⬇️ Humidity (esp. indoor)
3) ⬇️ Sunlight/Vitamin D

(2/n)
A twitter thread that demonstrates the importance of humidity on antiviral defense through mucociliary clearance measured by @Ericsongg. (3/n)

Read 11 tweets
10 Jan
What is the relevance of viral load in #COVID19 disease severity? A very talented @YaleMSTP student @SilvaJ_C found that saliva viral load to be a better predictor of disease than nasopharyngeal viral load. Here is a thread to explain the findings. (1/n)

medrxiv.org/content/10.110…
I preface by saying that numerous fantastic studies by many have demonstrated nasopharyngeal viral load to correlate with disease severity and mortality, while others do not find such correlation. Here are some of these studies. (2/n)
Being at @yale, the birthplace of #SalivaDirect and everything saliva bc of awesome colleagues like @awyllie13 @NathanGrubaugh @VogelsChantal et al, we had access to both saliva and nasopharyngeal (NP) samples from the same patients to do direct comparisons. (3/n)
Read 13 tweets
1 Jan
My first tweet of 2021 is going to be about 1 dose vs. 2 dose vaccine. I have tweeted in the past of the immunological advantages of a 2 dose vaccine. However, given the enhanced transmission variants on the rise, we need a modified strategy. (1/n)

theatlantic.com/science/archiv…
We typically give vaccines in more than one dose to increase 1) quantity, 2) quality, 3) longevity of antibody responses. This holds true for most vaccines including mRNA vaccines. Here is what I tweeted about this before. (2/n)

However, the 2 dose vaccine with limited number of vaccine means only half the people getting vaccinated at this time. If the virus is spreading slowly, we want to do the right thing and give the most vulnerable 2 doses and others to wait. (3/n)
Read 11 tweets
30 Dec 20
Inspired by this tweet by @TheMenacheryLab, I reached out to the wonderful colleagues at the @serimmune to see if the other mutations found in the B.1.1.7 variant would evade antibody responses generated by the wild type #SARSCOV2. (1/n)
According to this report, B.1.1.7 harbors non-synonymous mutations in the following viral genes, resulting in truncation, deletions and amino acid changes. Would these mutations result in evasion from antibodies generated by wild type virus? (2/n)

virological.org/t/preliminary-…
To probe this possibility, @serimmune used their technology platform based on bacterial display peptide libraries, next generation sequencing & machine learning to reveal antibody reactivity against WT and B.1.1.7 viral antigens. (3/n)

serimmune.com/technology.html
Read 11 tweets
26 Dec 20
What aspects of antibody responses determine the outcome of #COVID19? In this new preprint by @carolilucas @sneakyvirus1 et al., we found that the early timing of antibody response (before 14 days of symptom) in infected person is key to recovery. (1/n)

medrxiv.org/content/10.110…
As others have shown, we found that antibody levels from COVID patients correlated with disease severity.

journals.plos.org/plospathogens/…
wwwnc.cdc.gov/eid/article/26…

However, patients with lethal COVID did not have the highest level of anti-S or anti-RBD antibodies. What’s going on? (2/n)
To understand better the features of antibody responses in patients who died vs. survived, we compared their time course. We found a delay in antibody responses in lethal disease. We also noted patients with very high neutralizing Ab (HN) with very early antiviral Abs. (3/n)
Read 11 tweets
12 Dec 20
New exciting collaboration work with @Aaronmring lab reveals diverse and functional autoantibodies in #COVID patients.

Our findings provide clues for why COVID affects many organs, induce range of symptoms that are long lasting.

Thread (1/n)

medrxiv.org/content/10.110…
How do we look for autoantibodies against a wide range of self antigens? The @aaronmring lab developed a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) against 2,770 extracellular and secreted proteins "exoproteome" 💪🏼 (2/n)
A large fraction of #COVID patients had autoantibodies to multiple self antigens. The more severe the disease, more autoantibodies they had.(3/n)
Read 14 tweets
5 Dec 20
Here is a thread to explain the findings of this study, that used computational tools to predict T cell reactive sequences in #SARSCOV2 subunit vaccines.

The bottom line: there is no cause for alarm.

Here is why (1/n)
Our adaptive immune system has 2 types of white blood cells known as lymphocytes. T cells and B cells. These lymphocytes give us protection from wide variety of pathogens. Each lymphocyte has unique receptor that detect specific features of a pathogen. (2/n)
B cells detect pathogens structures through antibodies. T cells cannot detect pathogens on their own. They can only “see” pathogen when tiny pieces of viral proteins (peptides) are presented by molecules called major histocompatibility complex (MHC). (3/n)
Read 12 tweets
7 Nov 20
Do some people have cross-reactive antibodies to #SARSCoV2? If so, who are they? And are these cross-reactive Abs protective against #COVID19? A fascinating study by @KevinWNg et al provides answers. Thread. (1/n)

science.sciencemag.org/content/early/…
Do some people have cross-reactive antibodies? The answer is yes. SARS-CoV-2 Spike-reactive IgG was detected in 5 of 34 SARS-CoV-2-uninfected individuals with RT-qPCR-confirmed HCoV infection, as well as in 1 of 31 individuals without recent HCoV infection. (2/n)
Who has cross-reactive anti-spike antibodies? Mostly children and adolescents. The prevalence of SARS-CoV-2 S-reactive IgG antibodies peaked at 62% between 6 and 16 years of age. This age group is also the one in which antibodies to seasonal coronaviruses peak.(3/n)
Read 8 tweets
30 Oct 20
So happy to see a paper by my graduate student, Daniel Kim, chosen as a spotlight for the @JVirology 👏🏼 Daniel found that HSV-1 genome binds to RUNX1 and represses transcription of viral genes - a possible viral strategy to achieve latent infection. (1/n)

jvi.asm.org/content/94/22/…
Herpesviruses establish latent infection in neurons and leukocytes that express RUNX1 (transcription factor). Curiously, herpesvirus genomes are enriched in RUNX1 binding sites but not other viruses. (2/n)
Overexpression of RUNX1 but not RUNX3 (a related transcription factor that is not expressed in the cell type in which HSV-1 established latency) blunts HSV-1 infection in vitro. (3/n)
Read 5 tweets
25 Oct 20
As we approach the cold winter months in the Northern Hemisphere, I want to share these movies of mucociliary clearance (MCC) in the trachea of mice housed at 10% vs. 50% relative humidity (RH). Captured by @ericsongg (1/n)

This is MCC at 50% RH 👇🏽
And here is MCC of mice kept at 10% RH 👇🏽

For more, please read our original paper.

pnas.org/content/116/22…
(2/n)
MCC is a key mechanism of removal of inhaled particles, including viruses and bacteria. It is a primary defense mechanism of the respiratory tract. The dry air dehydrates the mucus and periciliary layer, impairing MCC. (3/n)

annualreviews.org/doi/abs/10.114…
Read 4 tweets
16 Oct 20
In this new Commentary, @SaadOmer3 and I discuss the birth & evolution of vaccine science, how vaccinations have changed our world, the current state of vaccines, remaining challenges & future outlook. #VaccinesSaveLives (1/n)

cell.com/cell/fulltext/…
Live attenuated vaccines worked well by themselves. But, immunization using toxoid alone induced poor immunity. #GastonRamon found that toxoid injected with ‘stuff’ incl. tapioca, lecithin, agar, starch oil, saponin or breadcrumbs improved immunity. (2/n)

tandfonline.com/doi/full/10.10…
While Alum became the adjuvant used in vaccines for past 100 years, there is a recent expansion in new adjuvants with potent capacity to boost immunity to vaccines. Discovery of pattern recognition receptors and their ligands laid foundation for this👇🏽 @YaleIBIO (3/n)
Read 6 tweets
30 Sep 20
Are you confused about the role of type I interferons (IFN) in #SARS_CoV_2 infection?

Here is my speculation on what makes IFN-I helpful vs. harmful in #COVID19 patients - it comes down to timing and dose. A short thread.

All figures made by @BioRender & @annsea_park (1/n)
In the best case scenario, a rapid and robust induction of IFN-I should result in viral control and mild disease. This may happen in young people, or with low viral exposure settings. For a discussion we wrote, please read this.
(2/n)
cell.com/cell-host-micr…
In older adults or after high dose viral exposure, impaired IFN response early during infection results in enhanced viral replication, and prolonged levels of IFN-I and IFN-III responses that could result in pathological consequences and severe disease. (3/n)
Read 9 tweets
13 Sep 20
I am the luckiest person in the world to have such wonderful trainees who organized the most amazing #IwasakiLabReunion/birthday zoom party yesterday. I am still in awe of how incredibly inspiring it was. Here are a few highlights I want to share with you. (1/) ImageImage
The event started with a delicious lunch delivered to my door for me and my family, to be followed later by my favorite dinner 🍣and 🎂 🍾 🎁 in the evening 😋 They really know how to spoil me! The entire day was packed with amazing talks, trivia sessions and Prince songs 💜(2/)
So 🙏🏼 to everyone who organized this incredible reunion and thoughtful presents - @maria_tokuyama @MelissaLV14 Kris Sepanek @jofrank1088 @JeffGehlhausen @Myoungjoo @peowenlu @carolilucas @aliceluculligan @tianyangmao @annsea_park @marioph13 @taka_takehiro @YYexin Pat Wong (3/)
Read 15 tweets
11 Sep 20
I cannot believe this is happening - we are celebrating our 20th anniversary of the Iwasaki Lab (and my 50th birthday) tomorrow 🎉

With presentations from my former and current trainees from all around the 🌎 I am suuuuper excited 😁 (1/) Image
The speaker list is just amazing 🤩 including @EllenFoxman @JennyLund15 @YosukeKumamoto @ImmunoFever Xinyan Zhao @weizmano @HShin_Lab @ericsongg Norifumi Iijima (2/)
All of this is hard to believe. The fact that my lab survived for 20 years, I was blessed with incredible trainees, such diverse people and science that supported the lab, and the next generation of scientists it fostered. Grateful does not begin to describe how I feel. (3/)
Read 5 tweets
7 Sep 20
An excellent new study by @BrodinPetter’s team on the differences between MIS-C and Kawasaki disease. This is incredibly timely and informative. Here are a couple of highlights. (1/)

cell.com/cell/fulltext/…
While there are some common features, MIS-C and Kawasaki disease differ in important areas. Non-overlapping symptoms and organ involvement, as well as the age group affected. Age in months in this study of MIS-C patients, 106 (71.1 - 165.4), and Kawasaki 24.5 (15.8 - 41.8). (2/)
Kawasaki disease patients have much higher levels of cytokines, IL-6, IL-17A and chemokine CXCL10, than either COVID-19 or MIS-C patients. (3/)
Read 6 tweets
28 Aug 20
A 25 yr old patient in Nevada has a confirmed case of #COVID19 reinfection (48 days apart between 1st and 2nd PCR).

This time, unlike the case in Hong Kong, the immune system did not protect this person from reinfection or disease. (1/n)

papers.ssrn.com/sol3/papers.cf…
During the 1st infection in April, patient recovered after about a month in isolation, testing negative for viral RNA in 2 subsequent tests. Patient was well until end of May, became ill and tested positive 2nd time. This time needing hospitalization & oxygen support. (2/n)
Viral genome of 1st and 2nd isolates differed significantly, indicating that reinfection occurred. (3/n)
Read 4 tweets
26 Aug 20
Men are at higher risk of developing more severe #COVID than women. Our paper out today by @taka_takehiro @Muhellingson Pat Wong @BenIsraelow @carolilucas @sneakyvirus1 Julio Silva @tianyangmao et al examines sex differences in immune response 👇🏽 (1/n)

nature.com/articles/s4158…
Here is a link to an accessible article. (2/n)

rdcu.be/b6tiP
Here is an earlier thread I wrote about this study.

We find that men decline in T cell responses as they age, and this correlates with worsening of #COVID disease. Women, even in old age, were able to stimulate T cell immunity. (3/n)

Read 7 tweets
24 Aug 20
A first case of #COVID19 reinfection from HKU, with distinct virus genome sequences in 1st and 2nd infection (142 days apart). Kudos to the scientists for this study.

This is no cause for alarm - this is a textbook example of how immunity should work.

(1/n)
1) Second infection was asymptomatic. While immunity was not enough to block reinfection, it protected the person from disease. (2/n)
2) Patient had no detectable antibody at the time of reinfection but developed detectable antibody after reinfection. This is encouraging. (3/n)
Read 5 tweets
18 Aug 20
Short🧵 on study by @BenIsraelow, @ericsongg et al on “Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling”.

Take home points
1) This is a quick and versatile model of #COVID19 that can be used on any genetic bgd 🐁

rupress.org/jem/article/21… Image
Mice are first transduced with AAV encoding human ACE2 to allow expression of viral receptor. This makes them susceptible to infection by #SARSCoV2. (red=virus; green=epithelia; blue=nuclei) Image
2) In this model, type I IFN signaling does not appear to contribute to viral control. In other words, #SARSCoV2 effectively evades innate immune control by endogenous IFN signaling. Image
Read 7 tweets
27 Jul 20
Very excited to share this work by the heroic team - @carolilucas Pat Wong @sneakyvirus @tiago21bio et al on “Longitudinal analyses reveal immunological misfiring in severe COVID-19”. A thread on our findings. #COVID19 #Pathogenesis (1/n)

nature.com/articles/s4158…
In this study, we enrolled COVID+ patients and analyzed their immune responses and viral load over the course of their hospital stay. We also compared samples from COVID- healthy health care workers (HCWs) as comparison. (2/n)
As reported by others, we found that COVID patients with severe disease have low T cell numbers and increased monocytes and neutrophils. We also found eosinophils come up in patients. This is bizarre 🧐 (3/n)
Read 16 tweets
22 Jul 20
How does the immune system work? Will there be #COVID19 vaccines? @BioRender & I put together ‘immunology 101 tweetorial for non-immunologists’. @jerryguartist, @shizaoki, @JungHeeSciViz also made this accompanying video. Please share widely! (1/n)

The immune system protects the host from invading pathogens through 2 layers: the innate and adaptive immunity. Innate immunity acts within minutes to remove the pathogen. Adaptive immunity takes days/wks but is specific & long lived, and is the basis for #vaccines. (2/n)
Innate immunity starts by triggering sensors that detect unusual molecules or activities, known as pattern recognition. Once microbial patterns are detected by these sensors (#PRR), they trigger immediate alarm through secretion of #cytokines and #interferons. (3/n)
Read 13 tweets