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Monica Gandhi MD, MPH Profile picture
@MonicaGandhi9
Apr 2, 2022 • 26 tweets • 11 min read • Read on X
Great article Science on cellular immunity, may help US on booster strategy "much focus in.. immunity surveillance has been on role of neutralizing antibodies..less emphasis on understanding role of T cells, memory B cells and non-neutralizing antibodies"
science.org/doi/10.1126/sc…
"Mounting evidence (I would argue we have known about T cells for long time!) suggests T-cell contributions to the host immune response are required for early, broad, and durable protection from SARS-CoV-2, especially in the setting of new variants of concern"; T cells provide
durable protection Want T cells across whole virus? Give whole virus vaccine. "Because Covaxin shows immune system the entire virus, the vaccine elicits a broad immunologic response not only against spike, but also against the receptor-binding domain, the
medpagetoday.com/opinion/second…
nucleocapsid protein of SARS-CoV-2, other parts of the virus. The vaccine also elicits strong cellular T-cell mediated immune responses, vital for long-term protection". Excellent tweet @profshanecrotty -multiple layers of protection in immune system
Cell paper focuses on durability of memory B cells: NO evidence of decay >9 months post vaccination. Boost will reactivate B cells to make antibodies, not needed if you already have high antibodies (eg 4th dose); breakthrough- same increase in Abs as boost
cell.com/cell/fulltext/…
As US debates 4th shot, ? comes up whether even 3rd shot makes B cells longer lasting; above paper did not show that. Below paper on T cells >80: 3rd shot increases antibodies but "CD4 T-cell frequencies reached similar levels after two and three doses "
thelancet.com/journals/lanin…
Important article that shows that every vaccination or exposure to COVID-19 expands and diversifies T cells
nature.com/articles/s4159…
Recent article about Omicron (>=32 mutations in spike) in vax'd: "despite mutations in spike protein, Omicron recognized by cellular component of immune system.. reasonable to assume protection from hospitalization and severe disease will be maintained"
jamanetwork.com/journals/jaman…
Please remember cellular immunity is not just T cells but also B cells- they produce antibodies if virus seen again aided by T cells but the antibodies are adapted to the variant they see in front of them
Question on whether variant-specific booster needed in future; study in above thread in macaques showed 3rd shot with "old" vaccine stimulated B cells & protected macaques to same extent as getting Omicron-specific booster due to B cells. New paper here:
nature.com/articles/s4158…
3rd shot (boost) increases frequency of Omicron-receptor binding domain (RBD) binding memory B cells, a site on spike protein that is more conserved across variants (part that sticks to cell). So, 3rd shot stimulates B cells that work across parts of virus same in all variants
Epidemiologically, we saw 3rd shot of great benefit to older individuals in terms of protection against severe disease during Omicron in this large VA study
This is why 4th shot likely will be needed for older individuals (and immunocompromised) in late summer to prepare for seasonal fall/winter respiratory pathogen season to protect these populations against severe disease
washingtonpost.com/outlook/2022/0…
If you read these long threads on cellular immunity, the ability of vaccines to prevent severe disease with COVID will become more clear; which is a HUGE benefit of vaccines
Amazing paper @SetteLab Cell today comparing cohorts Pfizer, Moderna, AztraZeneca, Novavax
1) 100% mRNA/Novavax vaccinees made CD4 cells
2) mRNA/AZ vaccinees similar % CD8 cells
3) Infection or AZ inc memory B cells
4) Antibodies wane; B/T cells stable
cell.com/cell/fulltext/…
CD4 and CD8 are T cells against SARS-CoV-2 and memory B cells being stimulated help produce more antibodies. Antibodies waning (or not working as well against variants) happening but preservation of B/T cells generated by vaccination very heartening
leaps.org/how-long-do-co…
Saw article yesterday -those with previous infection didn't have T cell response broadened by Omicron?Sample size tiny (6 prior Wuhan Hu-1 infection). Doesn't negate huge body of research on cellular immunity above. New test for cellular immunity below!
nature.com/articles/s4158…
The profound decoupling between cases & severe disease at this stage of the pandemic is mainly due to cellular immunity (for instance, Chicago has had zero COVID deaths June 6-10: chicago.gov/city/en/sites/…; Marin none since March) - B cells
T cells here:
Nice review why T cells so important to combat variants: "As we adapt to coexist with SARS-CoV-2"..need T cell assays. 1 large study (n=3000) w/ T-SPOT Discovery SARS-CoV-2 assay shows SARS-CoV-2–reactive T cells protect from COVID & last long time
science.org/doi/10.1126/sc…
This article explains why - even with BA4/BA5- rates of severe disease staying lower than any time since March '20 across much of the world due to cellular immunity @Medscape
medscape.com/viewarticle/97…
Although above cellular immunity thread has good papers, this review @profshanecrotty great (see figure). 1) Hybrid immunity strongest of all (if haven't had covid, hopefully #covaxin whole virus vax coming; 2) T/B cells last long from infection or vax
onlinelibrary.wiley.com/doi/10.1111/im…
TIMING OF BOOSTERS MATTER if you want to train B cell responses - wouldn't get until 6 months after last infection or booster; it is the presence of immune memory & cellular immunity that leads to uncoupling of cases & hospitalizations
time.com/6211075/covid-…
SPACING MATTERS: Another article showing us that hybrid immunity expands B cells to respond to all variants but that spacing matters for booster- extending interval expands B cells more (B cells adapt antibodies to variant they see)
journals.plos.org/plospathogens/…
One way to explain is that T cells expand with each booster/infection & that they protect you against severe disease; cover variants (even with mutations across the spike protein) as they have such an in-breadth, blanket response across the spike Image
Beyond the amazing vaccines for COVID, important to know about monoclonal antibodies, antiviral medications, and the other COVID vaccine candidates:
A simple primer I hope that explains how cellular immunity I wrote for @Medscape here
Exposure expands T cells: nature.com/articles/s4159…
Exposure expands potency & breadth of B cells:
nature.com/articles/s4158…
medscape.com/viewarticle/98…

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More from @MonicaGandhi9

Monica Gandhi MD, MPH Profile picture
Aug 30, 2023
HOW LONG DOES IMMUNITY LAST? To COVID vaccines or infection? We do not really know but there have been some really nice papers lately that give us more information. Please remember immunity divided into antibodies (which can come down & not work as well against variants)
IgA is one in the nose & mouth ("mucosa") that is raised by shots (vaccines) to certain extent but rise higher after natural infection; IgG is the one that is "humoral" or in the bloodstream. Many threads on here about cellular-mediated immunity: B & T cells cover all variants
This recent preprint is really important and summarized by @florian_krammer below in depth. Main take-aways: Breakthrough infections induce IgA (we knew) but protection from vaccine long-lasting even against former variants to severe disease/mortality
Read 8 tweets
Monica Gandhi MD, MPH Profile picture
May 3, 2023
RSV VACCINE FOR OLDER ADULTS: Respiratory syncytial virus (RSV) respiratory virus (most common after flu pre-COVID). 2 subtypes, A&B (1 dominates/season). Droplet; Recurrent infections. Most severe in neonates & adults >65; FDA approves 1st RSV vax today
msn.com/en-us/news/us/…
RSV vaccine 3 trials of new RSV vaccine, all published in the @NEJM recently so just to keep them straight- here is the vaccine which just got approved May 3 by the FDA for older adults. Remember our T/B cells so protection against severe disease higher!
nejm.org/doi/full/10.10…
A single dose of the RSVPreF3 OA vaccine had an acceptable safety profile and prevented RSV-related severe respiratory illness by 94% in adults>=60 years (71% against RSV infection, likely to fall with time as antibodies fall but severe disease protection will remain)
Read 4 tweets
Monica Gandhi MD, MPH Profile picture
Mar 21, 2023
NASAL VACCINES: To explain nasal vaccines, we have to explain the immune system first.
IgA is an antibody that helps attack the pathogen and exists in mucosal surfaces (like nose/mouth)
IgG is an antibody that is in the bloodstream
bbc.com/news/world-asi…
Cellular immunity is fantastic, redundant (so even if one cell line down in immunocompromised, have other), generated by either vaccine or infection; Comprised of
T cells- so in breadth from vax - works even across spike protein with its mutations
And the 2nd type of cell produced by vaccines or infection -B cell- amazing thing about B cells is that - if see omicron or one of its subvariants in future- they make antibodies adapted to that variant or subvariant (aided by T cells); adaptive immunity
Read 15 tweets
Monica Gandhi MD, MPH Profile picture
Mar 15, 2023
PUBLIC HEALTH POLICY: Seem to be at reckoning phase of COVID response- what worked, what didn't. Which interventions will be used in future pandemic responses? Interventions asked of public need good medical evidence for them (e.g. RCTs preferably, systematic reviews) to impose
In our field, Cochrane reviews represent best way to sum up the medical evidence to date by performing meta-analyses or systemic reviews of currently-available data; here is Cochrane on masks & other interventions for respiratory viruses including COVID
cochranelibrary.com/cdsr/doi/10.10…
Many asked past 3 years how CDC developed policies on masks (& age to mask), distancing (feet), ventilation, schools-> all non-pharmaceutical interventions. Originally theory-based. Now 3 years in, have data (RCTs highest level) to form policies from both US and other countries
Read 4 tweets
Monica Gandhi MD, MPH Profile picture
Mar 6, 2023
VACCINE DISCRIMINATION: We need to stop vaccine requirements for US entry like almost every other country. Am finishing COVID chapter for our ID "bible" & vaccines prevented transmission early on with alpha, but not enough now with current variants to justify such discrimination
Moreover, shame, stigma, blame (remember COVIDiots?), coercion, discrimination not good public health tools. When used for HIV, public health & ID physicians decried them but tactics used a lot in COVID. This book tries to explore & correct that for future
barnesandnoble.com/w/endemic-moni…
Concept of #harmreduction in pandemic responses means watching carefully if vulnerable people (like students, older people, low-income populations, migrants, sex workers, prisoners, those with disabilities, refugees, minorities) harmed more by response
nature.com/articles/s4146…
Read 4 tweets
Monica Gandhi MD, MPH Profile picture
Feb 8, 2023
FEAR: Some media & public health officials concerned Americans aren't fearful of COVID now. But the vaccines & therapeutics DO WORK. If we can't celebrate biomedical advances & imbibe their effectiveness (we have better tools for COVID than flu), what is point of developing?
In HIV medicine, when therapies came out, we didn't say to people- stay fearful; make this the controlling principle of your life. The book #Endemic I wrote (coming out July 11, 2023) hails these biomedical advances & the age we are in to fight pandemics to reassure the world
This is a rather brilliant summary of the issue from @benryanwriter
Read 4 tweets

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