Monica Gandhi MD, MPH Profile picture
Sep 29, 2021 18 tweets 6 min read Read on X
B CELLS ADAPT THEIR ANTIBODIES TO THE VARIANTS: This is article that showed antibodies & T cells durable (x 8 months) from 1-shot J&J but note: [We] "observed expansion of neutralizing antibody breadth against variants over time..." specifically delta
nejm.org/doi/full/10.10…
beta, gamma. "which suggests maturation of B-cell responses even without further boosting". This is not 1st paper that shows this. Natural immunity or vax generates B cells that go into memory and then they produce antibodies directed against variant they see (ADAPTIVE immunity)
So, I know people have asked about "variant specific boosters" or wanting to boost antibodies with original vax repeatedly, but original vax has mRNA or DNA in it that codes for the L ancestral SARS-CoV-2 strain, not the variants. Your immune system adapts if see virus again to
produce antibodies tailored to that variant. What are other papers? Here are some. This one from OHSU showing the memory B cells generated by the vaccines make antibodies directed towards the variant they are exposed to if variant seen
medrxiv.org/content/10.110…
And this paper shows that natural infection allows for ongoing evolution of neutralizing antibodies produced by memory B cells which are adaptive (also looked at hybrid immunity but vax didn't improve adaptation of in-breath antibodies)
biorxiv.org/content/10.110…
And this paper shows memory B cells keep increasing after mRNA vaccination 3 and 6 months after vaccination and they are able to cross-bind to different variants of concerns to produce adaptive antibodies against them (delta, etc.). Pretty cool
biorxiv.org/content/10.110…
The basis for a booster recommendation after 1 shot J&J is not on the immunologic research above but on finding that protection against severe disease (hospitalization) is not as robust (71%) as Pfizer (88%) and Moderna (93%)
cdc.gov/mmwr/volumes/7…
So please remember that it is not that adaptive immunity from B cells doesn't work & that they and T cells aren't there, the reason boosters got discussed for non-65 year olds, non-immunocompromised is due to so much circulating virus
Here is that preprint going on to full publication to show you how B cells adapt their antibodies to variants if they see the virus in the future. Delta? Okay, says B cells, I will make delta-specific antibodies.
science.org/doi/10.1126/sc…
This is not even speaking of T cells which you know are working to protect you against severe disease (and the T cells help these memory B cells produce antibodies) Image
IgA and IgG tweets-Antibodies produced by vaccine or infection. Naturally wane in nose and "mucosa" (respiratory tract) - susceptible to mild respiratory infection if circulating virus around you. T cells protect from severe disease; B cells take 3-5 days to make new antibodies
Hereafter will merge T and B cell threads, but thought you would be excited to see this paper. People have been concerned that B cells and T cells may go to lower levels in blood but that is not where they hang out long-term: go to lymph nodes and other biorxiv.org/content/10.110…
structures (bone marrow, lymphoid tissues, etc.) - "germinal centers". Paper shows memory B cells from vax not only in lymph nodes, but mature into LONG-LIVED memory plasma cells-to produce antibodies in future (memory B cells can activate 9 decades later)
nature.com/articles/natur…
Important article to add to this B cells thread on adapting to variants. Authors took individuals with recovered COVID (different disease severities), looked at B cells: short-lived plasma cells transiently secrete antibodies & die but long-lived B cells
academic.oup.com/jid/advance-ar…
traffic to the bone marrow/lymph nodes & and secrete antibodies (ADAPTED towards variants) for months to years’ post-infection if they see the virus again. Serologic studies like ones Pfizer/Moderna will do against Omicron don't capture that B cells will expand, and differentiate
into a NEW population of antibody secreting cells on repeat infection (with a variant or not). This important study showed that 1) memory B cells specific against the receptor binding protein of SARS-CoV-2 (not different in variants) develop even if initial infection asymptomatic
and doesn't mount antibodies ("seronegative") but diagnosed on PCR test; 2) Memory B cells stable, last to at least 1 year post-infection; 3) In contrast to plasma antibodies, the antibodies these B cells are programmed to secrete recognize ancestral AND variants of concern (RBD)
This is why Dr. Fauci and others not concerned that we will need an Omicron-specific booster because we have ADAPTIVE immunity - that is what the adaptive part means! B cells can adapt to variants
medpagetoday.com/infectiousdise…

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More from @MonicaGandhi9

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
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
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
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
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
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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