How do the various mutations within the SARS-CoV-2 variants impact vaccine-induced immunity? The amazing @carolilucas @VogelsChantal @InciYildirim11 led this study with with help from others to tackle this question - using 18 CoV-2 variants. (1/n)…
The study was designed to measure antibody and T cell immunity from people who were previously infected or not infected with SARS-CoV-2, before and after the 1st and 2nd doses of mRNA vaccines. Amazing effort by @InciYildirim11 @SaadOmer3 (2/n)
Antibodies to the ancestral S1 and RBD were induced in both prev. infected and uninfected vaccinees. S/S1/RBD-specific IgG levels in response to vaccination were significantly higher in the previously infected compared to uninfected, as reported by others. (3/n)
Next, neutralization activity of antibodies induced by the mRNA vaccines was measured through 50% plaque-reduction neutralization (PRNT50). Despite faster and higher NAb responses in previously infected, similar NAb levels were achieved after 2nd dose in both groups. (4/n)
Notice that even though every vaccinated person generated anti-Spike IgG responses, 2 individuals failed to induce neutralizing Abs even after the 2 shots. We don’t know the underlying cause yet. (5/n)
Next we examined CD4 and CD8 T cell responses to spike and nucleocapsid proteins. mRNA vaccines induced robust activation of CD4 T cells in both previously infected and uninfected vaccinees against ancestral and P.1 spike. (6/n)
In contrast, we found reduced CD8 T cell responses to the P.1 variant spike antigen compared to ancestral spike. This may be related to the various mutations in P.1 spike protein. Mutations are discussed below. (7/n)
Note that other studies found no reduction in T cell responses to ancestral vs. VOC spike antigens in vaccinated people. Difference may be due to assays or hosts. (8/n)

Ad26 vaccine:…
mRNA vaccines:…
How well do mRNA vaccine-induced antibodies work against variants? This is where having collaborators like @NathanGrubaugh is so powerful & enabling 💪🏼 He and his team have been surveying and studying every CoV2 variant in the community. (9/n)
We’re so lucky to tag team with @VogelsChantal in the Grubaugh lab who identified & provided 16/18 variants studied here. @carolilucas painstakingly propagated these variants and @VogelsChantal sequenced and validated each isolate. Spectacular team work! (10/n)
In addition to the spike, these variants have accumulated a number of mutations in other viral genes - important for viral transmission and immune evasion by the variants. This thread will only focus on the spike because that is what is used in mRNA vaccines. (11/n)
This 🏳️‍🌈 graph depicts the PRNT50 of antibodies induced in mRNA vaccinees against the ancestral vs. the 18 variants using authentic viral neutralization assays. You can see the various amino acid changes in the Spike correlating with reduction in NAb capacity. (12/n)
A linear mixed model by @jessroth95 revealed that 8 of the 11 key S gene mutations had significant negative effects on neutralization, and that L452R and E484K/Q had the greatest individual effects.(13/n)
ΔH69/V70 & E484K combination was synergistic (decreased neutralization more than the added effects; β=-0.182; p=0.005), L452R & P681R was antagonistic (decreased neutralization less than the added effects; β=0.228; p=0.003), and E484K & N501Y was neither (β=0.060; p=0.248). (14/)
Previously infected people had higher neutralization against variants than the uninfected in response to vaccination. Future vaccine boosters may help to overcome such NAb reduction observed for the variants with the L452R (B.1.617.2) or E484K & N501Y combo (P.1 , B.1.351). (15/)
Our study is a result of heroic efforts of many people, led by @carolilucas @VogelsChantal @InciYildirim11. Special thanks to Yale SARS-CoV-2 Genomic Surveillance Initiative, and the HCW volunteers for donating blood. @SaadOmer3 @NathanGrubaugh & I co-supervised this work. (End)
Adding this awesome thread by @NathanGrubaugh to accompany mine above. Much more deeper dive into the viral genetics, mutation comparison, community spread, and implications on vaccination strategies.

• • •

Missing some Tweet in this thread? You can try to force a refresh

Keep Current with Prof. Akiko Iwasaki

Prof. Akiko Iwasaki Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!


Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @VirusesImmunity

10 Jul
This thread is about alpha-gal syndrome (AGS) - meat allergy induced by tick bites. I’ve been living with AGS for >2 yrs. I hope this info will help those who suffer from this illness without knowing the cause. Please help bring awareness to #AGS (1/n)…
I live in New England USA, surrounded by beautiful nature. This nature is rich in wildlife - animals and arthropods including many species of ticks. (2/n)
Ticks are infamous for the many infectious agents they carry that cause diseases such as

Borrelia miyamotoi disease
Lyme disease
Powassan virus disease
Rocky Mountain spotted fever (RMSF)
Tularemia (3/n)…
Read 12 tweets
18 Jun
Latest preprint by @tianyangmao et al shows that a stem-loop RNA RIG-I agonist in mice can

1) Block viral replication and disease when given early after SARS-CoV-2 infection (including VOCs)
2)Eliminate chronic infection in immunodeficient mice

We urgently need antiviral agents that can work against any viral threats. Here, we use a stem-loop RNA developed by @AnnaPyle to trigger interferon to stimulate antiviral state. Work by @MelissaLV14 et al demonstrated robust ISG induction in mice👇🏽 (2/)…
First, we wanted to know if SLR can be used as a post-exposure prophylaxis. Mice infected with lethal dose of SARS-CoV-2 were treated with SLR 4 hours after exposure. SLR-treated mice had no detectable infectious virus 5 days later and most survived. (3/)
Read 11 tweets
14 May
It’s finally happening! I will be giving a talk today at the #AAI2021 with Dr. Fauci and Dr. Saif in the session, COVID-19 and the Science of Pandemics (12-2PM ET).

My talk will be on “Protective vs. harmful immune responses in COVID-19”. See you there!…
Amazing to listen to Dr. Fauci talk about the decades of basic research that led to the success of COVID vaccines. #AAI2021

“Effectiveness of the vaccines in real world setting is stunning - in every single age group.”
Exciting talk by Dr. Saif focuses on all things mucosal immunity! Secretory IgA, tissue-resident memory B cells and T cells are key to confer durable mucosal immunity. #AAI2021

SARS-CoV-2 infects not only respiratory mucosa, but also found in the gut, eyes and oral cavity.
Read 4 tweets
29 Apr
After many months of planning and hard work by so many (incl. @hmkyale @Dianaberrent @wade_schulz @CharleszYaleMed @Aaronmring @DaisySMassey @JeffGehlhausen), today, we are launching our research study to understand how vaccination may help improve #longcovid. 🧵 (1/n)

Pls RT🙏🏼
This study will examine how vaccines might improve the symptoms of #LongCovid. We are recruiting people with long covid (PCR+, Ab+, T-test+, or COVID diagnosed by medical doctor) who live in Connecticut, >18 years old, and have not received vaccines yet but are planning to. (2/n)
To participate in this study, you will be asked to complete 4 online surveys and provide blood and saliva 3 times at sites in New Haven Connecticut. If you are interested in participating, please email (3/n)
Read 10 tweets
10 Apr
New study by @MHitchingsEpi et al shows that an inactivated vaccine CoronaVac is effective against COVID-19 in a setting of epidemic P.1 variant transmission in Brazil 🇧🇷. A thread. (1/n)…
The authors conducted a matched test-negative case-control study to estimate the effectiveness of an
inactivated vaccine, CoronaVac, in healthcare workers in Manaus, where P.1 accounted for ~75% of the circulating virus.(2/n)
Vaccination with at least one dose was associated with an adjusted vaccine effectiveness of 49.6% (95% CI, 11.3 - 71.4) against symptomatic SARSCoV-2 infection >14 days after receiving the first dose. (3/n)
Read 8 tweets
9 Apr
An important thread from @PutrinoLab about why we should not be excluding PCR/Ab negative #LongCovid from analysis. So proud of @PutrinoLab for refusing to succumb to reviewers’ demand -which would have resulted in exclusion of data from underrepresented minorities. (1/)
I wish to highlight the importance of their study in this short thread and why I think it should be published ASAP. 84 people with long covid were examined for various symptoms in a retrospective cross-sectional observational study.(2/)…
First, look at the demographic data of those with #LongCovid. Compared to acute severe COVID (in older adults, male>female), long haulers appear more skewed towards women of younger age. (3/)
Read 7 tweets

Did Thread Reader help you today?

Support us! We are indie developers!

This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Too expensive? Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal Become our Patreon

Thank you for your support!

Follow Us on Twitter!