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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
Nov 8
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/)

science.org/doi/10.1126/sc…
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/) Image
Read 16 tweets
Prof. Akiko Iwasaki Profile picture
Oct 13
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/) Image
Read 11 tweets
Prof. Akiko Iwasaki Profile picture
Oct 11
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…Image
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/) Image
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/)
Read 8 tweets
Prof. Akiko Iwasaki Profile picture
Oct 4
Keynote talk by @MichaelPelusoMD. “#LongCovid is not a mystery anymore. Working with patients, I have optimism that we can figure this out.” #YaleCIISymposium Image
An excellent framework in thinking about the pathogenesis of #LongCovid
@MichaelPelusoMD Image
Where we need to go @MichaelPelusoMD Image
Read 4 tweets
Prof. Akiko Iwasaki Profile picture
Oct 2
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/)

sciencedirect.com/science/articl…
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/) Image
Read 4 tweets
Prof. Akiko Iwasaki Profile picture
Sep 27
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…
Image
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/) Image
Read 9 tweets

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