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Prof. Akiko Iwasaki Profile picture
@VirusesImmunity
Dec 30, 2021 • 11 tweets • 5 min read • Read on X
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CoronaVac is an inactivated SARS-CoV-2 vaccine approved for use in 48 countries. In collaboration with the Ministry of Health in Dominican Republic, we tested whether CoronaVac (2x) + Pfizer booster induces neutralizing Abs to Delta and Omicron. (1/)

medrxiv.org/content/10.110…
We analyzed plasma samples from 101 participants in Dominican Republic (DR) who received the BNT162b2 booster >4 weeks after the 2x of CoronaVac. We compared them to samples from people at Yale who received 2x of BNT162b2.
⬆️ ⬆️ Ab induced by heterologous prime & boost.(2/)
Next, @carolilucas & @ValterVSM analyzed NAb against ancestral vs. Delta variant. CoronaVac 2x followed by Pfizer mRNA vax booster robustly elevated NAb against both virus types, level similar to 2x Pfizer vaccine. (3/)
Just focusing on Pfizer 2x, omicron had the highest escape from neutralization compared to other VOCs (using authentic virus isolates), reducing the NAb PRNT50 levels by 11.9x compared to ancestral virus. Similar data have already been reported by others. (4/)
In CoronaVac fully vaccinated (2x) people, there was NO detectable neutralization against the infectious Omicron virus. Antibodies were assayed at mean days from second Coronavac shot of 113 days (with SD 33 days). (5/)
However, after the Pfizer mRNA booster, CoronaVac recipients elicited detectable levels of neutralization against omicron. Note that PRNT50 is reduced by 7.3x against Omicron compared to the ancestral virus. (6/)
How does prior infection modify neutralization against Omicron? In the mRNA vaccine recipients (28 days after second dose), prior infection provided advantages in cross protection against VOCs, including Omicron. (7/)
Unfortunately, in the CoronaVac 2x recipients boosted with Pfizer mRNA vax, prior infection made no difference to the neutralization capacity against Omicron. (8/)
Immunologically, this difference is interesting. Prior infection only synergies with the mRNA vax to elevate broadly neutralizing Ab but not with inactivated vax. This may relate to the persistent GC responses in mRNA vax reported by @TheBcellArtist. (9/)
nature.com/articles/s4158…
In terms of public health, CoronaVac 2x is insufficient to neutralize Omicron. Even with CoronaVac 2x plus Pfizer booster, NAb is only 1.4x higher than 2x mRNA alone. Thus, CoronaVac recipients may need 2 additional booster doses to reach levels needed against Omicron. (10/)
Lots of amazing folks from Dominican Republic and Yale contributed to this work. Special thank you to @SVermund for orchestrating this collaboration, and Drs. Eddy Perez-Then and Marija Miric for their leadership in DR. Always fantastic @carolilucas @ValterVSM 👏🏼 👏🏼 (end)

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More from @VirusesImmunity

Prof. Akiko Iwasaki Profile picture
Jun 19
Sharing our new study by @keylas3, @SilvaJ_C, Rafael Bayarri Olmos et al (with T. Horvath & @PutrinoLab) showing that a passive transfer of IgG from patients with #longCOVID into mice recapitulates ⬆️ pain and other symptoms 🧵 (1/)

medrxiv.org/content/10.110…
Long COVID disease pathogenesis includes persistent SARS-CoV-2 virus, dysbiosis, herpesvirus reactivation, autoimmunity, and others. In this study, we focus on the role of autoantibodies. (2/) Image
Among the original Mount Sinai-Yale Long COVID study participants 👇🏼 (with @PutrinoLab), we focused on patients with high neurological symptom burden (n=55), and compared antibodies with convalescent controls (n=42) or uninfected controls (n=39). (3/)
nature.com/articles/s4158…
Read 20 tweets
Prof. Akiko Iwasaki Profile picture
Jun 19
What determines whether someone gets infected or not after exposure to SARS-CoV-2? A new study by Lindeboom et al examined this question with COVID-19 human challenge study. @BenIsraelow and I summarize their key findings in this News & Views 🧵 (1/)
nature.com/articles/d4158…
The study: 16 healthy young volunteers with no prior infection or vaccination were inoculated nasally with a low dose of pre-Alpha SARS-CoV-2 strain. Interestingly, only 6 had sustained infection, 3 had transient, and 7 had abortive infection at this dose. (2/) nature.com/articles/s4158…Image
The three infection outcomes allowed investigation of key features associated with susceptibility vs. resistance. Higher baseline expression of HLA-QA2 mRNA was associated with COVID resistance. Early nasal interferon I response was seen in those with transient infection. (3/) Image
Read 10 tweets
Prof. Akiko Iwasaki Profile picture
Apr 22
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/) Image
Read 11 tweets
Prof. Akiko Iwasaki Profile picture
Mar 3
Delighted to share our latest work on #longCOVID - sex differences in symptoms and immune signatures. Led by @SilvaJ_C @taka_takehiro @wood_jamie_1 et al. with @LeyingGuan & @PutrinoLab. We find a striking inverse correlation btw testosterone levels and symptom burden👇🏼 (1/)

medrxiv.org/content/10.110…
This work leverages data from our recent Mount Sinai-Yale long COVID "MY-LC" study with the @PutrinoLab. This time, we asked the question, "Are there differences in symptoms and immune signatures of ♀️ vs. ♂️ with LC"? (2/)

nature.com/articles/s4158…
Image
While some symptoms were equally frequent in females and males, many were more frequent in females (e.g., swelling, headaches, muscle pain, cramps) than males. The top distinguishing symptoms of LC status by sex were hair loss in females and sexual dysfunction in males. (3/) Image
Read 16 tweets
Prof. Akiko Iwasaki Profile picture
Jan 13
In this prospective observational study, we examined changes in symptoms & immune phenotypes in vaccine-naïve people with #LongCovid after COVID-19 vaccination. Due to the timing of the initiation of this study, we were only able to recruit 16 people. However, the insights we gained are intriguing. Led by @connorbgrady, @bornali_27, @silva_JC, @hmkyale et al. (1/)
medrxiv.org/content/10.110…Image
This study was initiated in collaboration with @Survivor_Corps @dianaberrent based on their Facebook poll showing that 40% of respondents with self-reported Long COVID had mild to full symptom resolution after vaccination while 14% reported worsening of their symptoms. (2/)
doi.org/10.1101/2021.0…
In addition, evidence from other patient advocate groups, including @patientled and @longCovidSOS, and from @DanielGriffinMD, was emerging at the time on the impact of COVID vaccines in people with long COVID. (3/)
Read 19 tweets
Prof. Akiko Iwasaki Profile picture
Sep 25, 2023
So pleased to report that our Mount Sinai-Yale long COVID (MY-LC) paper with @putrinolab & others is now published!! Proud of the hard work of all who contributed. We found biological signatures that can distinguish people with vs. without #longCOVID (1/) nature.com/articles/s4158…
Question being asked: are there circulating cells & immune factors that are distinct in people with #longCOVID (LC) vs. those who recovered from COVID (convalescent control; CC) or those who never had COVID (healthy control; HC)? We studied 268 participants to address this. (2/) Image
Most participants were infected during the first wave in 2020, and studied on average about a year after the infection. Most were not hospitalized at acute phase and ~2/3 were female. We examined plasma factors, blood leukocytes & antibodies to SARS2, other viruses & self (3/) Image
Read 11 tweets

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