New study results challenge the idea that vaccine immunity fades quickly

Opposite findings in preprint —

Preprint - The Majority of SARS-CoV-2 Plasma Cells are Excluded from the Bone Marrow Long-Lived Compartment 33 Months after mRNA Vaccination
Doan C Nguyen; Ian T Hentenaar; Andrea Morrison-Porter; David Solano; Natalie S. Haddad; Carlos Castrillon; Pedro A Lamothe; Joel Andrews; Danielle Roberts; Sagar Lonial; Ignacio Sanz; Frances Eun-Hyung Lee

The goal of any vaccine is to induce long-lived plasma cells (LLPC) to provide life-long protection. Natural infection by influenza, measles, or mumps viruses generates bone marrow (BM) LLPC similar to tetanus vaccination which affords safeguards for decades. Although the SARS-CoV-2 mRNA vaccines protect from severe disease, the serologic half-life is short-lived even though SARS-CoV-2-specific plasma cells can be found in the BM.

To better understand this paradox, we enrolled 19 healthy adults at 1.5-33 months after SARS-CoV-2 mRNA vaccine and measured influenza-, tetanus-, or SARS-CoV-2-specific antibody secreting cells (ASC) in LLPC (CD19-) and non-LLPC (CD19+) subsets within the BM.

All individuals had IgG ASC specific for influenza, tetanus, and SARS-CoV-2 in at least one BM ASC compartment. However, only influenza- and tetanus-specific ASC were readily detected in the LLPC whereas SARS-CoV-2 specificities were mostly excluded. The ratios of non-LLPC:LLPC for influenza, tetanus, and SARS-CoV-2 were 0.61, 0.44, and 29.07, respectively. Even in five patients with known PCR-proven history of infection and vaccination, SARS-CoV-2-specific ASC were mostly excluded from the LLPC. These specificities were further validated by using multiplex bead binding assays of secreted antibodies in the supernatants of cultured ASC. Similarly, the IgG ratios of non-LLPC:LLPC for influenza, tetanus, and SARS-CoV-2 were 0.66, 0.44, and 23.26, respectively.

In all, our studies demonstrate that rapid waning of serum antibodies is accounted for by the inability of mRNA vaccines to induce BM LLPC.


Link | PDF (Preprint: MedRxiv) [Open Access]
 
Persistent immune imprinting occurs after vaccination with the COVID-19 XBB1.5 mRNA booster in humans
M. Alejandra Tortoricic; Amin Addetia; Albert J Seo; Jack Brown; Kaiti Sprouse; Jenni Logue; Erica Clark; Nicholas Franko; Helen Chu; David Veesler

Highlights
    • XBB.1.5 COVID-19 mRNA vaccine elicits neutralizing antibodies against current variants
    • Depletion of Wuhan-Hu-1 S-reactive plasma antibodies abrogate XBB.1.5 neutralization
    • XBB.1.5 COVID-19 mRNA vaccine primary recalls Wuhan-Hu-1 S-reactive memory B cells
Summary

Immune imprinting describes how the first exposure to a virus shapes immunological outcomes of subsequent exposures to antigenically related strains. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron breakthrough infections and bivalent COVID-19 vaccination primarily recall cross-reactive memory B cells induced by prior Wuhan-Hu-1 spike mRNA vaccination rather than priming Omicron-specific naive B cells.

These findings indicate that immune imprinting occurs after repeated Wuhan-Hu-1 spike exposures, but whether it can be overcome remains unclear. To understand the persistence of immune imprinting, we investigated memory and plasma antibody responses after administration of the updated XBB.1.5 COVID-19 mRNA vaccine booster. We showed that the XBB.1.5 booster elicited neutralizing antibody responses against current variants that were dominated by recall of pre-existing memory B cells previously induced by the Wuhan-Hu-1 spike. Therefore, immune imprinting persists after multiple exposures to Omicron spikes through vaccination and infection, including post XBB.1.5 booster vaccination, which will need to be considered to guide future vaccination.

Link
 
Persistent immune imprinting occurs after vaccination with the COVID-19 XBB1.5 mRNA booster in humans
M. Alejandra Tortoricic; Amin Addetia; Albert J Seo; Jack Brown; Kaiti Sprouse; Jenni Logue; Erica Clark; Nicholas Franko; Helen Chu; David Veesler

Highlights
    • XBB.1.5 COVID-19 mRNA vaccine elicits neutralizing antibodies against current variants
    • Depletion of Wuhan-Hu-1 S-reactive plasma antibodies abrogate XBB.1.5 neutralization
    • XBB.1.5 COVID-19 mRNA vaccine primary recalls Wuhan-Hu-1 S-reactive memory B cells
Summary

Immune imprinting describes how the first exposure to a virus shapes immunological outcomes of subsequent exposures to antigenically related strains. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron breakthrough infections and bivalent COVID-19 vaccination primarily recall cross-reactive memory B cells induced by prior Wuhan-Hu-1 spike mRNA vaccination rather than priming Omicron-specific naive B cells.

These findings indicate that immune imprinting occurs after repeated Wuhan-Hu-1 spike exposures, but whether it can be overcome remains unclear. To understand the persistence of immune imprinting, we investigated memory and plasma antibody responses after administration of the updated XBB.1.5 COVID-19 mRNA vaccine booster. We showed that the XBB.1.5 booster elicited neutralizing antibody responses against current variants that were dominated by recall of pre-existing memory B cells previously induced by the Wuhan-Hu-1 spike. Therefore, immune imprinting persists after multiple exposures to Omicron spikes through vaccination and infection, including post XBB.1.5 booster vaccination, which will need to be considered to guide future vaccination.

Link

Could someone explain the implications of this please? Am struggling even to read. What is " immune imprinting?" And how should it guide " future vaccination."
 
Sars-CoV-2 vaccine-elicited immunity after B cell depletion in Multiple Sclerosis.
"Noravax homologous boosting induced a significantly more robust serological response than mRNA boosting"

Abstract
The impact of B cell deficiency on the humoral and cellular responses to SARS-CoV2 mRNA vaccination remains a challenging and significant clinical management question. We evaluated vaccine-elicited serological and cellular responses in 1) healthy individuals who were pre-exposed to SARS-CoV-2 (n = 21), 2) healthy individuals who received a homologous booster (mRNA, n = 19; or Novavax, n = 19), and 3) persons with multiple sclerosis on B cell depletion therapy (MS-αCD20) receiving mRNA homologous boosting (n = 36). Pre-exposure increased humoral and CD4 T cellular responses in immunocompetent individuals. Novavax homologous boosting induced a significantly more robust serological response than mRNA boosting. MS-α CD20 had an intact IgA mucosal response and an enhanced CD8 T cell response to mRNA boosting compared with immunocompetent individuals. This enhanced cellular response was characterized by the expansion of only effector, not memory, T cells. The enhancement of CD8 T cells in the setting of B cell depletion suggests a regulatory mechanism between B and CD8 T cell vaccine responses.

https://journals.aai.org/immunohori...-CoV-2-Vaccine-Elicited-Immunity-after-B-Cell
 
https://www.imperial.ac.uk/news/232396/immune-imprinting-causes-varied-patterns-protection/

Immune imprinting causes varied patterns of protection against COVID-19 variants
by Emily Head03 December 2021

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"Research shows that the first SARS-CoV-2 spike protein a person encounters, be it by vaccination or infection, shapes their subsequent immune response

That is, it imparts different properties that have an impact on the immune system’s ability to protect against current and future variants, and also affects the rate of decay of protection.

The study is published today in Science by a team from Imperial College London and Queen Mary University of London. It is funded by UKRI."
 
SARS-CoV-2 spike protein found in the acrosyringium and eccrine gland of repetitive miliaria-like lesions in a woman following mRNA vaccination
Shigetoshi Sano; Mayuko Yamamoto; Reiko Kamijima; Hozumi Sano

Letter —

A 53-year-old woman presented with asymptomatic small vesicles and reddish papules in her extremities, which lasted for 15 months after the 3rd dose of mRNA vaccine (Pfizer/BioNTech). The lesions appeared repeatedly one after another and some developed small ulcers but were self-limiting, leaving brownish discoloration on the skin. Histopathology revealed intracorneal and contiguous intraepidermal sweat ducts. [...] Surprisingly, the SARS-Cov-2 SP was detected immunohistochemically in the cornified and spinous layers, where the sweat ducts were located. Further, SP staining in the cornified layer was mostly co-stained with carcinoembryonic antigen (CEA), which is a marker for the eccrine gland and duct. This confirmed that SARS-Cov-2 SP was expressed in the sweat ducts and, seemingly, the sweat retained in the affected lesion.

This case provides us with many puzzling issues about PVD [post-mRNA vaccine dermatoses]. First, the mRNA vaccine unexpectedly remained for a long period of time (over 1 year) after the last dose, although it was designed to be degradated shortly after administration. Similar to the present study, we previously reported two PVD cases with varicella or erythema multiforme-like dermatitis lasting for 3 months in which the SP was observed in either the blood vessels or eccrine glands. [...] this patient also complained of continuous headache, brain fog, fatiguability, and slight fever after the last dose

Link | PDF (The Journal of Dermatology)
 
Previous reports from this group —

Persistent varicella zoster virus infection following mRNA COVID-19 vaccination was associated with the presence of encoded spike protein in the lesion
Mayuko Yamamoto; Misaki Kase; Hozumi Sano; Reiko Kamijima; Shigetoshi Sano

BACKGROUND
Since the campaign of vaccination against COVID-19 was started, a wide variety of cutaneous adverse effects after vaccination has been documented worldwide. Varicella zoster virus (VZV) reactivation was reportedly the most frequent cutaneous reaction in men after administration of mRNA COVID-19 vaccines, especially BNT162b2.

AIMS
A patient, who had persistent skin lesions after BNT162b2 vaccination for such a long duration over 3 months, was investigated for VZV virus and any involvement of vaccine-derived spike protein.

MATERIALS & METHODS
Immunohistochemistry for detection of VZV virus and the spike protein encoded by mRNA COVID-19 vaccine. PCR analysis for VZV virus.

RESULTS
The diagnosis of VZV infection was made for these lesions using PCR analyses and immunohistochemistry. Strikingly, the vaccine-encoded spike protein of the COVID-19 virus was expressed in the vesicular keratinocytes and endothelial cells in the dermis.

DISCUSSION
mRNA COVID-19 vaccination might induce persistent VZV reactivation through perturbing the immune system, although it remained elusive whether the expressed spike protein played a pathogenic role.

CONCLUSIONS
We presented a case of persistent VZV infection following mRNA COVID-19 vaccination and the presence of spike protein in the affected skin. Further vigilance of the vaccine side effect and investigation for the role of SP is warranted.

Link | PDF (Journal of Cutaneous Immunology and Allergy) [Open Access]


A case of persistent, confluent maculopapular erythema following a COVID-19 mRNA vaccination is possibly associated with the intralesional spike protein expressed by vascular endothelial cells and eccrine glands in the deep dermis
Hozumi Sano; Misaki Kase; Yukiko Aoyama; Shigetoshi Sano

Here, we report an 86-year-old Japanese woman presenting with confluent maculopapular erythema, which developed following the second dose of COVID-19 Messenger RNA (mRNA) vaccine (BNT162b2).

Link | PDF (The Journal of Dermatology)
 
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Could someone explain the implications of this please? Am struggling even to read. What is " immune imprinting?" And how should it guide " future vaccination."

When immunising with a whole-antigen such as a whole spike protein, and the immune system has previously developed an adaptive response to this antigen, specifically along with dormant B-cell germinal centres in the lymph, exposure to a new antigen doesn't develop the same level of immune response to the new antigen because the rate of clearance of that new antigen is affected by the pre-existing adaptive immune response.

If the researchers were smart they'd know an obvious solution - don't use whole protein, just immunise against the key neutralising regions such as the RBD and a few other regions that researchers have identified as conserved regions of the spike protein for which antobodies also cause neutralisation (prevents the virus from actually infecting cells). In the case of the RBD, if the pre-existing antibody responses are poor at binding the new RBD variant then there will be more antigen available to be presented to B-cells over time in the germinal centres for them to develop more specific responses.
 
Merged thread

NHS rolls out new variant Covid vaccine as virus continues to kill 100 a week


People aged 75 years and older, residents in care homes for older people, and those aged six months and over with a weakened immune system will be offered a dose of COVID-19 vaccine

The NHS has begun administering booster jabs of the Covid vaccine as the virus continues to claim 100 lives a week in England.

The jab will be offered to those aged 75 and above, residents in care homes for the elderly, and individuals aged six months and over with compromised immune systems. Appointments will be scheduled between now and June, prioritising those at highest risk. If you're turning 75 between April and June, there's no need to wait until your birthday - you can get vaccinated when called upon.


You may receive an offer for the vaccine from your GP, or you can book through the NHS app on Apple or Android devices. You can also locate your nearest walk-in vaccination site via the NHS website. Those receiving the jab will be given a booster dose of a vaccine produced by Pfizer or Moderna and approved in the UK. These vaccines have been updated from their original versions to target different COVID-19 variants.

NHS rolls out new variant Covid vaccine as virus continues to kill 100 a week - Mirror Online
 
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Yes, I've just booked the next instalment. It's crazy they're not making it more widely available, given that sort of death rate. :arghh:

I read a report from Zoe last week saying they had removed their figures. They were reporting higher levels ( can't remember number) and realised that more people were reporting pos than neg results which would distort the figures. The Zoe study likes both pos and neg results if a covid test is taken.

I have been offered next vac but won't be taking it, not advisable after last experience.
Was at hospital yesterday for four hours and we were the only ones wearing masks apart from receptionist who wore it below her nose.None of clinical staff in treatment room, about 8/9, wore masks. They still had soap dispensers everywhere.

edit: last sentence of para 1 added for clarity
 
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