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Prof. Akiko Iwasaki Profile picture
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1 Jan, 11 tweets, 5 min read
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)
Unfortunately, the vaccine roll-out is much slower than we had expected. This means that even the vulnerable have to wait for months to get their 2 shot vaccines. (4/n)

statnews.com/2020/12/29/pub…
In the meantime, the virus is mutating and spreading faster. A mutant virus with 50% ⬆️ in transmission kills a lot more people than a mutant with 50% ⬆️ in lethality. A must read thread from @AdamJKucharski 👇🏽 (5/n)

So how effective is a single dose vaccine? We do not know for sure, but for at least a month or more, a single shot mRNA vaccines should provide ~90% protection (>14 d post vaccination). This is from the Moderna VRBPAC Briefing Document. (6/n)
Whether a single dose vaccine provide protection from severe COVID is not clear due to small sample size and short follow up duration. (7/n)
I am still a proponent of 2 dose vaccine but given the urgency, we can delay the 2nd dose until more vaccines become available. I know many others have been saying this all along, but it was the B.1.1.7 variant transmission rate that did it for me. (8/n)

The good thing about the mRNA vaccine is that if you prime with it, you can boost with other types of vaccines (viral vectored, DNA, mRNA…etc). In the future, a mixed prime boost vaccine strategies can be tested to provide long term protective immunity. (9/n)
So how long can we safely wait in between 1st and 2nd doses? If you look at the childhood vaccine schedules, some boosters are given months to years apart. For COVID vaccine, booster after a few months might be okay. (10/n)

cdc.gov/mmwr/preview/m…
Well I guess things are already moving along faster than I can type (but @EricTopol types faster than the news) in both UK and US. Posting my thread now before it is completely obsolete (end).

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More from @VirusesImmunity

Prof. Akiko Iwasaki Profile picture
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
Prof. Akiko Iwasaki Profile picture
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
Prof. Akiko Iwasaki Profile picture
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
Prof. Akiko Iwasaki Profile picture
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
Prof. Akiko Iwasaki Profile picture
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
Prof. Akiko Iwasaki Profile picture
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

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