Edward Nirenberg

@enirenberg

Views my own, but you can borrow them if you feel so inclined. Anti-disease. Negentropy hunter. Kosmotropophile. Big Nerd Energy. “A homework person.” Fun at parties. Antibody hoarder. “Problematically literate.” he/him

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Edward Nirenberg@enirenberg· Jun 29

Comic. First panel: 2 people and one says I suck. Second panel: other person removes top of the first one’s head like a lid. Third panel: second person pulls out first person’s brain. Final panel: second person holding the perspiring brain and threatening it with a knife saying “stop lying to my friend”

Edward Nirenberg@enirenberg· Jun 15

It turns out it massively broadened the immune response, enabling IIV to generate high antibody levels against 2 strains of H5 influenza (bird flu) that weren't included in the vaccine—something IIV alone was completely incapable of doing. There's another study about that out today: rdcu.be/fosRx

After day 20, mice vaccinated with IIV + mRNA lipid nanoparticles had significant antibody responses to 2 strains of H5 influenza viruses, whereas IIV alone did not induce any meaningful antibody response to these viruses (which are not present in the vaccine).

Edward Nirenberg@enirenberg· Jun 15

are especially potent inducers of TFH cells. They had a low dose IIV, high dose IIV, and IIV + an mRNA encoding GFP (green fluorescent protein) as a control condition, IIV + mRNA encoding IFN-β1, and IIV+ mRNA encoding IL-21 and watched the antibody response over time.

Mice were immunized on day 0 and 21 with IIV and an mRNA-lipid nanoparticle encoding either GFP (negative control), IFN-β1, or IL-21 and their antibody responses were tracked over time. The IL-21 and IFN-β condition had the most durable responses with the highest antibody levels at day 374. The team also measured the ability of the plasma cells in the bone marrow to secrete antibodies to influenza on day 434. The IL-21 and IFN-β mRNA group had the greatest number of these plasma cells, with essentially none detectable from IIV alone by day 434 even under the high dose condition. GFP mRNA appeared to enhance the production of these plasma cells with a low dose of IIV, though it was much smaller than what was seen for IL-21 and IFN-β.

Edward Nirenberg@enirenberg· Jun 15

Both of those cytokines were shown to be major enhancers of the antibody response in the previous set of experiments and were not meaningfully induced by IFN-β, but IL-12 did induce IL-21. However, this is specific to humans. IL-12 does not induce IL-21 in mice. IL-21 and IFN-β were...

The addition of IL-12 to IIV markedly enhances the induction of IL-21, with similar effects at moderate and high doses. In contrast, IFN-β has no meaningful induction of IL-21 and may even suppress it compared with IIV alone. It is proposed that IL-12 helps to generate TFH cells, which are critical for helping B cells make antibodies, and the TFH cells make IL-21.

Edward Nirenberg@enirenberg· Jun 15

They key difference was that the nasal spray vaccine (LAIV) induced a strong type 1 interferon response, whereas the shot (IIV) showed no real ability to trigger it at all. But it turns out that if you add IFN-β, you fix that deficit. LAIV also induced IL-12 and IL-21 more than IIV.

Organ donor spleens were used to create spleen organoids which were then vaccinated with inactivated or live attenuated flu vaccine. Cytokine levels were measured on day 3 and antibody levels were measured on day 7. In examining the cytokine responses between the two vaccines, it was seen that the live attenuated vaccine induced a much better type 1 interferon response than the inactivated. However, adding back interferon beta to the inactivated vaccine essentially reproduced the cytokine response.

Direct measurements of cytokines in donor spleen organoids on day 3 comparing live attenuated vaccine and inactivated vaccine to controls.

Measurements of the 3 types of interferons produced on day 3 in spleen organoids between the inactivated, live, and control conditions. There is similarity in the induction of type 2 interferons between the two vaccines but type 1 and type 3 are markedly higher for the live attenuated.

Edward Nirenberg@enirenberg· Jun 15

Okay, back to the paper. The team wanted to tease apart which of these cytokines was actually causing the high-quality immune responses as opposed to just being a bystander. To do this, they took human tonsil and spleen organoids, gave the flu vaccine and added cytokines at 3 doses.

The team used human spleen and tonsil organoids, vaccinated them with influenza vaccines, then measured how the antibody response was affected by the addition of cytokines at 3 concentrations ( 1 ng/mL, 10 ng/mL, and 100 ng/mL; except for IL-1β (10× lower for each concentration) and IL-18 (10× higher for each concentration)).

Edward Nirenberg@enirenberg· Jun 15

The findings were interesting. 3 cytokines had the strongest effect: IL-18, GROα (CXCL1), and IFN-β. One of the other interesting findings was that the direction of the effect differed for the same cytokine between hi vs lo responders, such as for CD40L and IFN-β. What do these cytokines do?

Fig. 2 | Meta-analysis identified a correlation between pre-VAX serum abundance of cytokines and post-VAX antibody response against the flu vaccine (IIV). We examined the correlation for 66 cytokines across the cohorts included in Table 1. The correlations were performed separately in groups with low or high pre-VAX flu HAI antibody (Ab) titers, as defined in Fig. 1b. log 10 P values of the correlations were provided with the sign denoting the direction of the correlations (positive or negative slopes). FDRs were reported for significant

or borderline significant hits. Random effect meta-analysis was performed to calculate effect sizes and standard errors; z tests were performed, all statistical tests were two-sided, and multiple-comparison adjustment was applied using the Benjamini–Hochberg FDR method. Exact FDR-adjusted P values can be found in Source Data Fig. 2.# P < 0.05, *P < 0.1. Further methodological details are provided in the Supplementary Methods.

Edward Nirenberg@enirenberg· Jun 15

They decided to split the group into those who had high levels of antibody against flu before vaccination as those in the top 50% of the group and those who had low levels as in the bottom 50%. They looked at 66 cytokines in the pre-vaccine samples and asked which ones predicted antibody response.

Study set up: participants donated blood before vaccination with an inactivated flu vaccine, had their antibody levels measured before vaccination, then had them measured afterwards on day 28, and had the fold change measured between day 0 and day 28. The fold change had a general trend of being greatest in those with the lowest pre-vaccine antibody levels, which is expected, but was consistently lower among those 65 and older.

Edward Nirenberg@enirenberg· Jun 15

The team had access to samples from 581 individuals collected across flu seasons and using their samples they were able to get measurements of a lot of immunity parameters, like cytokine levels before and after vaccination, which they then used to see why some people had good vs poor responses.

Table 1 | Summary of influenza vaccine cohorts and sample characteristics

Cohort

Flu vaccine study 15

Flu vaccine study 17

Flu vaccine study 18

Flu vaccine study 28

Total participants

Clinical Trials no.

NCT01827462

NCT03020537

NCT03022396

NCT03088904

Flu seasons

2013

Age

Med (min–max)

70 (22–90+)

70 (8–90+)

44 (2–89)

22 (12–50)

65 (2–90+)

Sex

2009

2010

2014

2015

(female %)

79

45

39

0

n = 581

70

43

82

0

56

7

20

0

48

0

0

25

67

0

0

0

56%

64%

54%

72%

58%

Edward Nirenberg@enirenberg· Jun 8

It turns out that infectious diseases can obey borders. So long as the preventive measures are concentrated on a particular side. Seems like we could just choose to vaccinate across both sides of a border and make it a non-issue for everyone. I prefer that option. @voices4vaccines.bsky.social

Edward Nirenberg@enirenberg· Jun 5

Shoot, I didn't realize.

Members of the American Diabetes Association (ADA) were escorted by police out of the convention center in New Orleans during the organization's annual meeting on Friday as they handed out copies of an editorial criticizing Trump administration changes to U.S. biomedical research.

Among them was Steven Kahn, MBChB, the lead author of the editorial, which published online in late April in the organization's flagship journal, Diabetes Care. Kahn is also the editor in chief of the journal.

Kahn, Aaron Kelly, PhD, past ADA president Desmond Schatz, MD, Justin Ryder, PhD, Irl Hirsch, MD, and at least one other member were handing out printed copies of the editorial outside of a keynote speech given by an NIH official. NIH Director Jay Bhattacharya, MD, PhD, was supposed to give the talk, but pulled out at the last minute, Kahn told MedPage Today.

Kahn said ADA leadership had inserted a statement in the editorial that the organization "had nothing to do with the writing of this manuscript. That is their insert."

The ADA did not return a request for comment from MedPage Today as of press time.

A video taken by MedPage Today shows Kelly, a pediatric obesity expert from Minnesota, being shoved by an officer wearing a badge of a local Constable's office, with Louisiana State Police following close behind. A plainclothes security agent rips the editorials from Kahn's hands.

Kahn is then asked to step outside with the officers and security detail.

In a separate video provided to MedPage Today, Kahn and Ryder were shown outside of the convention center talking with police after they were escorted outside. Kelly, who was also outside taking the video, said they were "threatened to be arrested for handing out the editorial."

"They physically grabbed us, forced us out of the conference center, and now are telling us we can no longer attend this meeting. They're taking our lanyards," Kelly said.

"It really has come to this in America. Censorship is real," said Kelly. "Ameri…

Edward Nirenberg@enirenberg· Jun 2

E.g., this case. A patient in a trial for an antidepressant and presented to the emergency department with what looked like shock after taking 29 of the pills in a suicide attempt. Then it turned out he was in the placebo group. He was fine 15 minutes later. www.sciencedirect.com/science/arti...

Mr. A was pale and diaphoretic with a blood pressure of 80/40 and heart rate of 110. He was tremulous, and respirations were rapid. Examination was otherwise unremarkable. An intravenous line was inserted, blood drawn and infusion of normal saline begun. Acetaminophen and salicylate levels were zero, urine drug screen was negative and other laboratory studies were within normal limits. After receiving 2 L of normal saline, blood pressure rose but again dropped when the infusion was slowed. Over 4 h, he was given approximately 6 L of fluid. He remained lethargic with a blood pressure of 100/62 and heart rate of 106. At this point, a physician from the clinical trial arrived and determined that Mr. A had taken placebos. When informed of this, the patient expressed surprise then almost tearful relief. Within 15 min, he was fully alert, blood pressure was 126/80, heart rate was 80.

Edward Nirenberg@enirenberg· Jun 2

When I first started reading this I thought it could be attempting to suggest that [at least some of] long COVID reflects a functional neurological disorder-type condition (which I think would be worth exploring) and the more I read on the more I just... no. This part in particular was... yikes.

Believing patients, all patients, means that mind-body therapies may work in some cases of long Covid, even severe ones. (Dismissing those therapies as the “placebo effect” is, ironically, to reaffirm their effectiveness: The placebo effect is just a pejorative term for the power of the mind to produce symptom improvements.)

Edward Nirenberg@enirenberg· May 25

Currently working between several projects and these are my emotional support tabs

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Edward Nirenberg@enirenberg· May 23

We absolutely should have hantavirus vaccines (at the very least to offer to people at high exposure risk) and ideally pan-hantavirus vaccines. But this is entirely being done to curry political favor. Kennedy transferred funding for mRNA technologies directly to the pet project of Matthew Memoli...

Secretary Kennedy

@SecKennedy
Today, I signed a targeted PREP Act declaration to support the development and deployment of medical countermeasures related to Andes virus, which can cause the deadly respiratory illness Hantavirus Pulmonary Syndrome.

This action helps remove barriers to research and response efforts while we continue monitoring the recent outbreak linked to the South Atlantic cruise ship. HHS is taking this situation seriously and will continue working to protect public health and support the safe development of potential treatments and countermeasures.

Edward Nirenberg@enirenberg· May 22

Or this one. "Custom metabolism test," which measures cortisol, DHEA-S, homocysteine, thyroid function, B12, folate, glucose, and hemoglobin A1c. All for the low, low price of ~$500.

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Edward Nirenberg@enirenberg· May 22

This is just ridiculous. Serum leptin tests have very few indications and it isn't just a matter of having greater hunger and difficulty losing weight. The main context this matters for is lipodystrophy and severe (potentially monogenic) obesity.

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Edward Nirenberg@enirenberg· May 21

Me looking at rhythm strips for ventricular quadrigeminy vs ventricular parasystole:

The Devil Wears Prada screenshot of Andrea saying "You know, it's just that both those belts look exactly the same to me"

Edward Nirenberg@enirenberg· May 20

My entire day: Several group chats with disjoint membership: I think you have impostor syndrome. phone call with a colleague: I think you have impostor syndrome. Made me think of this:

keuhkopussirotta Follow
My life has been so much better ever since I traded my impostor syndrome to brilliant conman
-syndrome. Do I deserve anything in life? Fuck no!
Will I grasp it anyway? Fuck yes!
My art has never been worth shit, but watch me bullshit my way into art school! I am a horrid goblin, but watch me make these people like me! Am I qualified to do this task? Well I sure have the certificates that say that I am! And how did I get those? Who knows! Not me! I am so good at cheating, I don't have to break a single rule to do it!
I am brilliant, fast, and absolutely drunk with power!
drpathetique Follow
Finally a concise, accurate description of what l've been doing the past ten years

Edward Nirenberg@enirenberg· May 19

plausibly affect to help ensure that matching of vaccinees and non-vaccinees was fair). But... there was still a slightly lower risk of these in vaccinees compared with non-vaccinees. One of the other findings was a lower risk of cancer mortality. No way that could be real, right?

Outcome
wHR
Traumatic injury
All
0.94 (0.94 - 0.95)
Unintentional injury
All
0.91 (0.90 - 0.92)

Table 3. RI of Short-Term Mortality, All Causes, by Cancer, External Causes, Circulatory Diseases, and COVID-
19, Within 6 Months Following Vaccination, Using Adapted SCCS Models?
Table 3. RI of Short-Term Mortality, All Causes, by Cancer, External Causes, Circulatory Diseases, and COVID-19, Within 6 Months Following Vaccination, Using Adapted SCCS Models*
Abbreviations: RI, relative incidence; SCCS, self-controlled case series. a The few events occurring on the day of vaccination were considered separately.
• When the RI of the first vaccine dose is estimated, second doses (should they occur) are suppressed, but counts of deaths that occur during such second-dose exposure periods are adjusted to account for the fact that second doses were suppressed. To estimate the vaccination effect (RI), a pseudo-likelihood approach is implemented in R. This is done by replacing the event count n with n/RI2, where RI2 is the RI of the second dose. Second doses are suppressed when Ris of the first dose are estimated because the presence and timing of such second doses may be affected by the event occurring after the first dose. 34

Edward Nirenberg@enirenberg· May 19

Anyway, while we let the statistics sort itself out, I think it's worth asking a question. The basic origin of trained immunity is the induction of transcription factors that durably (i.e., multigenerationally) alter chromatin structure by microbial components. www.cell.com/immunity/abs...

Early experiments characterized trained immunity in monocytes and macrophages. They demonstrated that primary
exposure to microbial components, such as β-glucan or Bacillus
Calmette-Gue´rin (BCG), induces durable changes in cytokine
production and antimicrobial activity.7–9 These functional shifts
are accompanied by coordinated alterations in chromatin accessibility, histone modifications, transcription factor (TF) activity,
and metabolism.7–10 Although not antigen specific, such
changes form a stable state that improves the cell’s intrinsic
responsiveness to subsequent, often unrelated, challenges.
More recent work has expanded the concept of trained immunity to include other non-adaptive cell types. It is now appreciated that transient exposures to microbial ligands, vaccines, or
inflammatory cues can also induce long-lasting changes in the
molecular properties of monocytes, tissue-resident macrophages (TRMs), and hematopoietic stem and progenitor cells
(HSPCs), leading to enhanced inflammatory responses to
many different secondary stimuli

Edward Nirenberg@enirenberg· May 19

that nonspecific effects of vaccines are clinically meaningful for 24 of those. The 1 trial that didn't is within the expected rate of false positives. Moreover, it appears that adjustments for multiple comparisons (to avoid false positives) were not done correctly. They also selectively reported...

Table 1
Scoring of papers by Christine Stabell Benn and Peter Aaby reporting results for
trials on non-specific effects (NSE) of BCG and measles vaccines after correction
for multiple testing with Holm-Bonferroni method. A result reported in a paper is
considered to support a finding if it achieved statistical significance after
correction.
Criteria Description Count
(Yes/total)
Proportion
Yes
1 Main outcome of paper is primary
outcome of trial?
12/26 46 %
2a If Yes to criteria 1: Primary outcome
supports finding of an NSE?
1/12 8 %
2b If No to criteria 1: Main outcome of paper
supports finding of an NSE after HB(*)
correction?
0/14 0 %
3 Secondary outcomes of paper supports
finding of an NSE after HB(*) correction?
(**)
1/25 4 %
4 Authors interpret finding for main
outcome of paper as support for NSE?
7/26 27 %
5 Authors interpret finding for secondary
outcomes of paper as support for NSE?
(**)
23/25 92 %
(*) HB refers to Holm-Bonferroni correction - see text for details.
(**) This omits the one paper significant on the primary outcome

Edward Nirenberg@enirenberg· May 15

Also this is... extremely suspicious

Journal Metrics
Acceptance rate69%
Time to Desk Decision2 days
Submission to first decision21 days
Submission to final decision35-42 days
Acceptance to publication7 days
Article Downloads25369
Article Views100369

Edward Nirenberg@enirenberg· May 12

"Calm-mongering" is a new one for me (h/t @kmpanthagani.bsky.social) Anyway, I've never seen panic accomplish anything useful, so...

cnn
47m
It's true that Hantavirus is no Covid. Still, some health experts say that at points, the messaging has been too willing to dismiss the possibility of a threat. Statements meant to quell anxiety instead risk undermining trust if they later turn out not to be true.

HANTAVIRUS IS NOT COVID-19, BUT
'CALM-MONGERING' RISKS
TRIGGERING POST-COVID ANXIETY

Edward Nirenberg@enirenberg· May 12

I know some people are still really worried about how Andes virus (hantavirus) spreads. I thought a more thorough explanation of what we do/don't know could be useful for addressing that. open.substack.com/pub/deplatfo...

People are panicking over how hantavirus spreads. They seem to be missing a few key points.
Airborne or not airborne isn't the whole story.

Deplatform Disease

deplatformdisease.substack.com

Edward Nirenberg@enirenberg· May 11

See also: syphilis (which is obviously not a virus but the same idea) pmc.ncbi.nlm.nih.gov/articles/PMC...

From the very beginning, syphilis has been a stigmatized, disgraceful disease; each country whose population was affected by the infection blamed the neighboring (and sometimes enemy) countries for the outbreak. So, the inhabitants of today’s Italy, Germany and United Kingdom named syphilis ‘the French disease’, the French named it ‘the Neapolitan disease’, the Russians assigned the name of ‘Polish disease’, the Polish called it ‘the German disease’, The Danish, the Portuguese and the inhabitants of Northern Africa named it ‘the Spanish/Castilian disease’ and the Turks coined the term ‘Christian disease’. Moreover, in Northern India, the Muslims blamed the Hindu for the outbreak of the affliction. However, the Hindu blamed the Muslims and in the end everyone blamed the Europeans [4-6].

Edward Nirenberg@enirenberg· May 11

Anyone, know what a "mildly positive" PCR result means? I'm guessing they mean that the Ct value is high, but who knows?

See new posts
Conversation
HHS
@HHSGov
HHS through
@ASPRgov
and
@CDCgov
is supporting
@StateDept
in the repatriation of 17 American citizens from the MV Hondius cruise ship affected by the Andes variant of hantavirus.

All 17 are currently en route via
@StateDept
airlift to the United States, with two of the passengers travelling in the plane's biocontainment units out of an abundance of caution. One passenger currently has mild symptoms and another passenger tested mildly PCR positive for the Andes virus.

As of now, the airlift will transport passengers to the ASPR Regional Emerging Special Pathogen Treatment Center (RESPTC) at the University of Nebraska Medical Center/Nebraska Medicine in Omaha, Nebraska before taking the passenger with mild symptoms to a second RESPTC at its final destination.

Upon arrival at each facility, each individual will undergo clinical assessment and receive appropriate care and support based on their condition.
10:00 PM · May 10, 2026
·
24.3K
Views

Edward Nirenberg@enirenberg· May 9

“So it’s basically like a bowl of cheetococci” - @druvbhagavan.bsky.social

White round bowl with silver spoon containing jalapeño cheddar protein puffs shaped as small spheres

Edward Nirenberg@enirenberg· May 7

And... there it is.

Mary Talley Bowden MD
@MaryBowdenMD
Follow
I'll be selling ivermectin for Texans only, no prescription needed....
- 12mg, 100 count, $85
- 18mg, 100 count, $110
Made in the USA. Stay tuned.

Edward Nirenberg@enirenberg· May 7

I wanted to give a bit of an update on the whole Hantavirus situation given the amount of concern I'm seeing about it: open.substack.com/pub/deplatfo...