Excited to share our work by @BenIsraelow et al published today. We asked what are the roles of antibodies vs. T cells in controlling primary infection, reinfection, and vaccine-mediated protection? (1/n)

science.org/doi/10.1126/sc…
First, we asked if B cells are needed to control primary infection. We used muMT mice (devoid of B cells) transduced with AAV-hACE2. These mice had only a slight delay in viral clearance. Thus B cells are not necessary for controlling primary SARS-CoV-2 infection. (2/n)
However, in mice that have neither T cells nor B cells (RAG-/-), SARS-CoV-2 persisted with no sign of clearance. Thus, innate immunity is insufficient, and adaptive immunity is required to control primary infection. (3/n)
These findings have important implications in the persistent SARS-CoV-2 infection we see in immunocompromised patients, and imply that defects in T and B cell immunity predispose people for chronic COVID infection. (4/n)
Next, we wanted to know if CD4 vs. CD8 T cells are required for clearance of primary SARS-CoV-2 infection. Depletion of CD4 or CD8 had moderate effects on loss of viral control. However, depletion of both CD4 and CD8 T cells resulted enhanced viral replication. (5/n)
What is the role of CD4 T cells in primary SARS-CoV-2 clearance? It turns out that the role of CD4 T cells is mainly to support antibody production (panel D), because in the absence of B cells (panel C), CD4 depletion had little impact on viral control. (6/n)
Are T cells or Ab sufficient to control primary infection with SARS-CoV-2? @BenIsraelow collected either sera (Ab) or T cells from infected mice at 14 days, and transfer to RAG-/- host, which were challenged with virus. Turns out that Ab > T cells in controlling virus. (7/n)
Next, we asked whether mRNA vax or natural SARS-CoV-2 infection establishes lung-resident CD8 T cells. While both induced comparable circulating CD8 T cells (IV+), natural infection >> vax in establishing tissue-resident CD8 T cells (IV-). #mucosalimmunity (8/n)
How well does the mRNA vax or primary infection protect against VOC, and how much of that depends on CD8 T cells? Great news is that the mRNA vax or prior infection protected 100% of mice, even after CD8 T depletion at the time of challenge. (9/n)
In the lungs of these mice, we found that both mRNA vax mice and convalescent mice were completely protected from disease with original strain (WA1) and the B.1.351 virus. Even without CD8 T, all vax & convalescent mice eliminated infectious virus (G).(10/n)
Further, by immunizing with varying doses of the mRNA vax, @BenIsraelow found a strong correlation between anti-spike IgG levels, neutralizing Ab and protection against COVID-19 disease. (11/n)
In conclusion, while T cells were sufficient for the clearance of primary infection, they were not required for protection against reinfection or vaccine-mediated protection. (12/n)
We did not test the sufficiency of T cells in vaccine-mediated protection. However, a very nice study by @Masopust_Vezys shows the promise of adding T cell antigens to vaccines. (13/n)

pubmed.ncbi.nlm.nih.gov/34193597/
While we did not test the Delta variant, with its high viral load and transmission capacity, vaccines that induce mucosal immunity (TRM, IgA) may become important to better prevent infection and transmission. (14/n)

news.yale.edu/2021/09/02/imm…
As usual, this project was enabled by a great team work. Led by the amazing @BenIsraelow @YaleIDFellows with key collaborators @tianyangmao @sneakyvirus1 @ericsongg @biobridget & @SaadOmer3 🙏🏼 (end)

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More from @VirusesImmunity

6 Sep
I am very proud of @marioph13, @peowenlu and @ValterVSM for participating in #scicomm. They explained viral plaque assay, flow cytometry and ELISA to news reporter from WAPA TV 🇵🇷 via @dacolon

Me: Cloro no, vacuna sí! (1/)

wapa.tv/programas/cuar…
Here is @Marioph13 explaining viral plaque assay en español 🤩 (too bad his excellent explanation did not make it into the video clip) (2/)
Here, @ValterVSM explains ELISA, how it can detect levels of antibodies in a person, and what antibody levels mean for protection against SARS-CoV-2 VOCs 💪🏼 (3/)
Read 6 tweets
10 Aug
In this new Neuroview in @NeuroCellPress, I discuss "How COVID-19 has transformed my science”. Recounting my personal journey of how I responded to the pandemic, and how the pandemic has transformed the way I do science. Some lessons learned. (1/n)

cell.com/neuron/fulltex…
Glad to highlight my amazing colleagues who made team science possible. The Yale IMPACT team, Albert Ko, @SaadOmer3 @NathanGrubaugh @ShelFarFar @CharleszYaleMed @EllenFoxman Allison Nelson & many others. @wade_schulz opened my 👀 to the power of data science (2/)
Yale IMPACT team made quite a contribution on our understanding of viral transmission, detection, disease and immunology behind COVID-19. @EricTopol says it best👇🏽 (3/)

Read 11 tweets
19 Jul
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)

medrxiv.org/content/10.110…
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)
Read 17 tweets
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)

resident360.nejm.org/clinical-pearl…
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

Anaplasmosis
Babesiosis
Borrelia miyamotoi disease
Ehrlichiosis
Lyme disease
Powassan virus disease
Rocky Mountain spotted fever (RMSF)
Tularemia (3/n)

portal.ct.gov/DPH/Epidemiolo…
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

🧵(1/)
biorxiv.org/content/10.110…
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/)

advances.sciencemag.org/content/4/2/e1…
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!

immunology2021.org/scientific-pro…
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

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