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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
May 16
Published today! Victoria Bastos, @KerrieGreene_ et al found two distinct immunotypes of ME/CFS based on the cerebrospinal fluid analysis. Great collaboration with @MBVanElzakker @microbeminded2 and the Bragée clinic in Sweden. (1/)
academic.oup.com/jimmunol/artic…
This is perfect timing as Victoria will present these data at the @polybioRF symposium today. (2/)

polybio.org/spring-2025-sy…Image
Based on cerebrospinal fluid cytokines, we identified two clusters of ME/CFS patients. Cluster 1 had elevated matrix metalloproteinases & many cytokines compared to cluster 2. Other than older age (Cluster 1), clinical presentation of these clusters was similar. (3/) Image
Read 5 tweets
Prof. Akiko Iwasaki Profile picture
May 13
Published today📣
Our nasal booster in the "Prime & Spike" vaccine works without adjuvants (which are needed to induce adaptive immunity but also cause inflammation). @Kwon_Dongil @tianyangmao @BenIsraelow et al. asked how this is possible. (1/)
nature.com/articles/s4159…
Prime & Spike is a vaccine strategy that leverages preexisting immunity primed by conventional vaccines to elicit mucosal IgA and T cell responses that prevent COVID infection and transmission in rodents. The nasal booster is simply the spike protein (2/) science.org/doi/10.1126/sc…
Our new study shows that the nasal spike protein booster converts lymph node memory B cells into IgA-secreting cells in the lung with the help of memory CD4 T cells. Ag-specific CD4 T cells replace all the necessary functions of adjuvants without nonspecific inflammation! (3/)
Read 5 tweets
Prof. Akiko Iwasaki Profile picture
May 10
This prospective observational study led by @connorbgrady @bornali_27 @SilvaJ_C @hmkyale examined the impact of the primary COVID-19 vaccination on the symptoms and immune signatures of 16 people with #longCOVID. Here is what we found 👇🏼 (1/)

nature.com/articles/s4385…
This study asked: Does COVID vaccination improve symptoms of long COVID? If so, is the improvement due to robust T and B cell responses leading to the clearance of the viral reservoir? If not, is there an immune feature that predicts worsening of LC? (2/)
The self-reported impact of vaccination was variable. Of the 16 long COVID patients, 10 felt better, 3 had no change, and 3 had worse health (1 hospitalized) 12 weeks after vaccination. Both physical and social effects of symptom burden appeared to decrease after vaccination. (3/)Image
Read 6 tweets
Prof. Akiko Iwasaki Profile picture
Feb 20
Our preprint on post-vaccination syndrome is out. We studied immune signatures and examined spike protein in the blood of people who have developed chronic illnesses after COVID-19 vaccination. (1/) medrxiv.org/content/10.110…
Vaccines have saved countless lives and inspired me to become an immunologist. While generally safe, some people experience adverse effects, including Post-Vaccination Syndrome (PVS). Studying PVS is crucial for improving patient care and enhancing vaccine safety & acceptance. (2/) pubmed.ncbi.nlm.nih.gov/37986769/
To explain the study and results, @MalloryLocklear wrote this excellent summary. (3/)
news.yale.edu/2025/02/19/imm…
Read 6 tweets
Prof. Akiko Iwasaki Profile picture
Nov 8, 2024
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, 2024
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

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