True, but I found FAR more concerning and noticeable THIS statement:
I have noted that one of the primary ingredients of the Lipid Nanoparticle delivery system is “ALC 1035” (two attachments, parts highlighted) in the Pfizer shots. The fourth attachment is the toxicity report on ALC-1035, which comprises between 30-50% of the total ingredients. 3 The Safety Data Sheet, (attached as Exhibit B) for this primary ingredient states that it is Category 2 under the OSHA HCS regulations (21 CFR 1910) and includes several concerning warnings, including but not limited to:
- Seek medical attention if it comes into contact with your skin;
- If inhaled and If breathing is difficult, give cardiopulmonary resuscitation
- Evacuate if there is an environmental spill
- the chemical, physical, and toxicological properties have not been completely investigated
- Caution: Product has not been fully validated for medical applications. For research use only
25. Other journals and scientific papers also denote that this particular ingredient has never been used in humans before...
Now I WISH this copy of her statement included her ATTACHMENTS_--because "if" this "ALC-1035" IS PEG (Polyethylene Glycol) and IF it is the SAME Polyethylene Glycol used in laxatives--then
WHY would there be a "TOXICITY REPORT" on "ALC-1035" and WHY would this "TOXIC" substance "comprise between 30-50% of the total ingredients"? If "ALC-1035" IS "Polyethylene Glycol" then WHY is it listed as a Category 2 substance under OSHA regulations, necessitating the above warnings?
OBVIOUSLY, "ALC-1035" MUST be something QUITE DIFFERENT from normal "Polyethylene Glycol".
I've been trying to do a search on "ALC 1035"---came up dry, so tried "ALC 1035 Pfizer" and so far have found "some" concerning things---but all of them seem to indicate that ALC-1035" either IS polyethylene glycol, OR---that there's some missing piece to this puzzle I'm not getting yet. The use of PEG in laxatives and the WARNINGS about it which she cites above don't match---
and this is MORE than just her confusing "Polyethylene Glycol" with "Ethylene Glycol"---look again at her statement:
one of the primary ingredients of the Lipid Nanoparticle delivery system is “ALC 1035” (two attachments, parts highlighted) in the Pfizer shots.
AND
The fourth attachment is the toxicity report on ALC-1035,
For further review, I did find ONE tiny study done in Singpore, about anaphylactic reactions to the Polyethylene Glycol in the Pfizer shots. This is a PDF (link below) and I do note it mentions the "1035" figure as being something related to the Immunoglobulin G (IgG) which is (per Wikipedia) "IgG is the
main type of antibody found in blood and extracellular fluid, allowing it to control infection of body tissues. By binding many kinds of pathogens such as viruses, bacteria, and fungi, IgG protects the body from infection."
I copied only the Introduction, Description, and Conclusions of the study (it's 7 pages total if you go to the link)
Pseudo-Anaphylactic Reactions to Pfizer BNT162b2 Vaccine
https://www.mdpi.com › pdf
Case Report
Pseudo-Anaphylactic Reactions to Pfizer BNT162b2 Vaccine:
Report of 3 Cases of Anaphylaxis Post Pfizer
BNT162b2 Vaccination
Xin Rong Lim 1,* , Bernard Pui Leung 1,2, Carol Yee Leng Ng 3, Justina Wei Lynn Tan 1, Grace Yin Lai Chan 1,
Chien Mei Loh 3, Gwendolyn Li Xuan Tan 3, Valerie Hui Hian Goh 3, Lok To Wong 3, Chong Rui Chua 3,
Sze Chin Tan 1, Samuel Shang Ming Lee 1, Hwee Siew Howe 1, Bernard Yu Hor Thong 1 and Khai Pang Leong 1,3
Citation: Lim, X.R.; Leung, B.P.; Ng,
C.Y.L.; Tan, J.W.L.; Chan, G.Y.L.; Loh,
C.M.; Tan, G.L.X.; Goh, V.H.H.; Wong,
L.T.; Chua, C.R.; et al. Pseudo-
Anaphylactic Reactions to Pfizer
BNT162b2 Vaccine: Report of 3 Cases
of Anaphylaxis Post Pfizer BNT162b2
Vaccination. Vaccines 2021, 9, 974.
vaccines9090974
Academic Editor: Stefano D’Errico
Received: 5 July 2021
Accepted: 27 August 2021
Published: 31 August 2021
Copyright: © 2021 by the authors.
1 Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng,
Singapore 308433, Singapore;
bernard.p.leung@gmail.com (B.P.L.);
justina_tan@ttsh.com.sg (J.W.L.T.);
grace_yl_chan@ttsh.com.sg (G.Y.L.C.);
sze_chin_tan@ttsh.com.sg (S.C.T.);
samuel_lee@ttsh.com.sg (S.S.M.L.);
Howe_hwee_siew@ttsh.com.sg (H.S.H.);
bernard_thong@ttsh.com.sg (B.Y.H.T.);
khai_pang_leong@ttsh.com.sg (K.P.L.)
2 Health and Social Sciences, Singapore Institute of Technology, Singapore 138683, Singapore
3 Clinical Immunology Laboratory, Tan Tock Seng Hospital, Singapore 308433, Singapore;
carol_ng@ttsh.com.sg (C.Y.L.N.);
chien_mei_loh@ttsh.com.sg (C.M.L.);
Gwendolyn_TAN@ttsh.com.sg (G.L.X.T.);
Hui_Hian_Valerie_GOH@ttsh.com.sg (V.H.H.G.);
Lok_To_WONG@ttsh.com.sg (L.T.W.);
Chong_Rui_CHUA@ttsh.com.sg (C.R.C.)
* Correspondence:
xin_rong_lim@ttsh.com.sg; Tel.: +(65)-6357-7822; Fax: +(65)-6357-2686
Abstract: Anaphylactic reactions were observed after Singapore’s national coronavirus disease 2019 (COVID-19) vaccination programme started in December 2020. We report the clinical and laboratory features of three patients in our institution who developed anaphylactic reactions after receiving the Pifzer BNT162b2 vaccine. IgM and IgG antibodies, but not IgE antibodies to the Pfizer BNT162b2 vaccine, were detected in all subjects. Similarly, mild to high elevated levels of anti-polyethylene glycol (PEG) IgG (1035–19709 U/mL, vs. vaccine-naive < 265 U/mL, vaccine-tolerant < 785 U/mL) and IgM (1682–5310 U/mL, vs. vaccine-naive < 1011 U/mL, vaccine-tolerant < 1007 U/mL) were detected in two out of three patients via commercial ELISA. High levels of serum anaphylatoxin C3a
(79.0 6.3 g/mL, mean SD, vs. normal < 10 g/mL) were observed in all three patients during
the acute phase of the reaction, while tryptase levels, a marker of mast cell activation, were not
elevated. Finally, one patient with the highest levels of anti-PEG IgG, IgM, and anti-Pfizer BNT162b2
IgG and IgM exhibited an enhanced Th2
cytokine serum profile during an acute reaction, with high
levels of IL-4 (45.7 pg/mL, vs. vaccine-naive/tolerant < 2.30 pg/mL), IL-33 (86.4 pg/mL, vs. vaccinenaive/
tolerant < 5.51 pg/mL) and IL-10 (22.9 pg/mL, vs. vaccine-naive/tolerant < 12.49 pg/mL)
diminishing over time following corticosteroid treatment. Taken together, we propose these cases
of anaphylaxis described are driven by a complement activation-related pseudoallergy (CAPRA),
rather than classical IgE-mediated mechanisms.
Keywords: COVID-19; vaccine; anaphylaxis; antibodies; cytokines
1. Introduction
The United States (US) Food and Drug Administration (FDA) granted emergency
use authorization of the Pfizer BNT162b2 vaccine on 11 December 2020. On 6 January
2021, the US Centers for Disease Control (CDC) announced that there had been 21 cases of
anaphylaxis resulting from the Pfizer BNT162b2 vaccine in the period 14–23 December [1].
In this period, 1,893,360 first doses of the vaccine were administered, with a reaction rate
of 11.1 cases per million doses. Most of the reactions (71%) occurred within 15 min of
vaccination. A total of 17 of the 21 people had a documented history of allergies or allergic
reactions and seven had a history of anaphylaxis.
Singapore’s Health Sciences Authority (HSA) granted interim authorisation for the
Pfizer BNT162b2 vaccine under the Pandemic Special Access Route (PSAR) on 14 December
2020 [2] and the Moderna mRNA-1273 vaccine on 3 February 2021 [3]. As of 18 April
2021, amongst 2,213,888 doses of vaccine administered, there were 20 cases of anaphylaxis
reported with the Pfizer BNT162b2 and Moderna mRNA-1273 vaccines [4]. This is similar
to the incidence rates reported overseas of around 0.5 to 2 per 100,000 doses administered.
Our institution commenced Pfizer BNT162b2 vaccination on 30 December 2020. Within the
first 2 months of vaccine inoculation, there were five cases of anaphylaxis among healthcare
workers in our hospital, with three who consented to our study and fulfilled the Brighton
Collaboration Anaphylaxis Working Group’s case definition [5] (Table 1).
3. Case Presentation and Results
Patient 1, a 42-year-old male, developed flushing, periorbital edema, globus sensation,
and wheezing 30 min after the second dose of the Pfizer BNT162b2 vaccine (Table 1). He
has a history of poorly controlled asthma and urticaria to etoricoxib. He had developed
periorbital edema 3 days after the first dose of the Pfizer BNT162b2 vaccine and assumed
it was an unrelated event. Patient 1 was managed with two doses of intramuscular (IM)
adrenaline and monitored in the high dependency unit. He was hospitalized for 4 days
and received 9 days (2 days intravenous (IV), 7 days oral) of moderate-to-high dose
corticosteriods in total.
Patient 2, a 32-year-old female, developed erythema, flushing, breathlessness, globus
sensation, and wheezing 30 min after the first dose of the Pfizer BNT162b2 vaccine. She
has a history of well controlled asthma and mild, intermittent allergic rhinitis. After the
initial treatment (Table 1), the symptoms recurred at 8 and 27 h post-vaccination, requiring
repeated doses of IM adrenaline. She was hospitalized for 4 days in total and received
regular IV hydrocortisone and diphenhydramine throughout the admission.
Patient 3, a 40-year-old female, developed generalised urticaria, periorbital edema,
globus sensation, and breathlessness 20 min after receiving the second dose of the Pfizer
BNT162b2 vaccine. She has a history of mild, intermittent chronic rhinosinusitis, without
asthma or a history of non-steroidal anti-inflammatory drug hypersensitivity. She reported
numbness of her left forearm 20 min after the first dose of the Pfizer BNT162b2 vaccine
which resolved after 2 days. After initial treatment with IV hydrocortisone and diphenhydramine,
she was discharged after 2 days but returned the same evening complaining of
the recurrence of periorbital edema and globus sensation. She was admitted for another
2 days and required 7 days of moderate-to-high-dose corticosteriods.
4. Discussion
The Pfizer-BioNTech COVID-19 vaccine (BNT162b2) contains modified RNA encoding
the coronavirus spike protein encased by a polymer consisting of (4-hydroxybutyl)azanediyl)-
bis(hexane-6,1-diyl)bis (ALC-3015), (2-hexyldecanoate),2-[(polyethylene glycol)-2000]-N,Nditetradecylacetamide (ALC-0159), 1,2-distearoyl-snglycero-3-phosphocholine (DPSC), and
cholesterol. This vaccine contains several excipients and lipids, and currently PEG-2000 is
one of the excipients with recognised allergenic potential [7]. Clinical immunologists and
allergists have postulated that such reactions could be due to IgE-mediated mechanisms
via anti-PEG IgE or related to pre-existing PEG allergy via anti-PEG IgM or anti-PEG
IgG antibodies resulting in a complement activation-related pseudoallergy (CAPRA) [8,9].
Preexisting anti-PEG IgG/IgM triggers complement activation upon exposure to PEGylated
liposomes, resulting in the generation of anaphylatoxins C3a and C5a which activates
allergic effector cells such as macrophages, basophils, and mast cells [9]. These allergic
effector cells release a variety of inflammatory mediators that cause vascular leakage,
resulting in the clinical presentation of a pseudoallergy. PEGylated lipid nanoparticles
can also directly bind to these allergic effector cells via surface receptors and trigger the
secretory response of these cells [10]. While IgE independent pseudoanaphylaxis has been
demonstrated in animal models, it is still not clearly demonstrable in human pathology [11].
We observe that the clinical course of these three patients is protracted in nature,
lacks hypotension as a feature, has proclivity for symptom recurrence, and requires at
least 4–7 days of moderate-to-high-dose corticosteriods. All patients had elevated C3a
levels which decreased over time, while tryptase levels remained normal, supporting
pseudoallergic reactions as potential mechanisms via a complement activation-related
pseudoallergy (CAPRA). The presence of high IgG to PEG and the Pfizer BNT162b2
vaccine in Patient 2 and high IgG/IgM to PEG and the Pfizer BNT162b2 vaccine in Patient
3, and the lack of IgE antibodies suggest that the reactions could be induced by pre-existing
anti-PEG antibodies. Patient 1’s reaction could be induced directly by the vaccine lipid
nanoparticle activating the complement system, as both antibodies to PEG and the Pfizer
BNT162b2 vaccine are low. Anti-BNT162b2 IgG did not rise in all three patients 4 to 5 weeks
post-anaphylaxis, and we postulate that this might be related to the corticosteroids that
were given as treatment.
Our novel ELISA assay to detect antibodies to the Pfizer BNT162b2 vaccine involves
the coating of the Pfizer BNT162b2 vaccine on ELISA plates to allow the binding of antibodies
in serum samples against all potential immunogenic epitopes of the vaccine. Further
work is required to determine the precise immunogenic epitope of these antibodies directed
against the COVID-19 vaccine, whether it is to the PEG component or pegylated
lipid nanoparticle of the vaccine. The lack of anti-BNT162b2 IgE and trypase response
is intriguing, suggesting a potential mast cell and type 1 hypersensitivity independent
event. This was confirmed by employing two different anti-human IgE antibodies in our
assays (BD Pharmingen (San Diego, CA, USA) and Sigma-Aldrich (Merck KGaA, Germany)),
and additional IgG depletion assays to rule out competitive binding, with all
samples < 2.5 standard deviations of optical density from the blank.
Studies have shown that the prevalence of anti-PEG antibodies in healthy populations
ranges from 20 to 44% [12]. Population studies are required to determine the prevalance of
anti-PEG or anti-BNT162b2 antibodies and to determine a cut-off value that could serve
as a diagnostic test to distinguish the at-risk population who will develop anaphylaxis to
mRNA COVID-19 vaccines.
5. Conclusions
To date, the cause of anaphylaxis post mRNA COVID-19 vaccination remains unclear.
Many authors postulate that PEG could be a potential allergen via IgE- and non-IgEmediated
mechanisms [8–10]. Further studies are required to dissect the immunological
mechanisms of anaphylaxis post COVID-19 mRNA vaccination, with larger cohorts for
the prevalance of anti-PEG and/or anti-BNT162b2 antibodies, and to establish a potential
cut-off value for COVID-19 mRNA vaccine-related anaphylaxis.
References
1. CDC COVID-19 Response Team; Food and Drug Administration. Allergic Reactions Including Anaphylaxis after Receipt of the
First Dose of Pfizer-BioNTech COVID-19 Vaccine - United States, December 14–23, 2020. MMWR Morb. Mortal. Wkly. Rep. 2021,
70, 46–51. [CrossRef] [PubMed]
2. Health Sciences Authority, Singapore. Interim Authorisation of Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) for Active Immunisation
to Prevent COVID-19 Disease in Singapore. Available online:
https://www.hsa.gov.sg/announcements/dear-healthcareprofessional-
letter/interim-authorisation-of-pfizer-biontech-covid-19-vaccine-(bnt162b2)-for-active-immunisation-toprevent-
covid-19-disease-in-singapore (accessed on 14 December 2020).
3. Health Sciences Authority, Singapore. HSA Grants Interim Authorisation for Moderna COVID-19 Vaccine in Singapore. Available
online:
https://www.hsa.gov.sg/announcement...ts-interim-authorisation-for-moderna-covid-19
-vaccine-in-singapore (accessed on 3 February 2021).
4. Health Sciences Authority, Singapore. MicrosoftWord—HSAs Safety Update on the COVID-19 Vaccines (18 April 2021)_Final
(cwp.sg). Available online:
https://www-hsa-gov-sg-admin.cwp.sg/docs/default-source/hprg-vcb/safety-update-on-covid1
9-vaccines/safety-update-no-1-on-covid-19-vaccines-(18-apr-2021) (accessed on 10 August 2021).
5. Rüggeberg, J.U.; Gold, M.S.; Bayas, J.M.; Blum, M.D.; Bonhoeffer, J.; Friedlander, S.; de Souza Brito, G.; Heininger, U.; Imoukhuede,
B.; Khamesipour, A.; et al. Brighton Collaboration Anaphylaxis Working Group. Anaphylaxis: Case definition and guidelines for
data collection, analysis, and presentation of immunization safety data. Vaccine 2007, 25, 5675–5684. [CrossRef]
6. Stone, S.F.; Cotterell, C.; Isbister, G.K.; Holdgate, A.; Brown, S.G. Emergency Department Anaphylaxis Investigators. Elevated
serum cytokines during human anaphylaxis: Identification of potential mediators of acute allergic reactions. J. Allergy Clin.
Immunol. 2009, 124, 786–792. [CrossRef] [PubMed]
7. Klimek, L.; Novak, N.; Cabanillas, B.; Jutel, M.; Bousquet, J.; Akdis, C.A. Allergenic components of the mRNA-1273 vaccine
for COVID-19: Possible involvement of polyethylene glycol and IgG-mediated complement activation. Allergy 2021.
[CrossRef] [PubMed]
8. Banerji, A.; Wickner, P.G.; Saff, R.; Stone, C.A., Jr.; Robinson, L.B.; Long, A.A.; Wolfson, A.R.; Williams, P.; Khan, D.A.;
Phillips, E.; et al. mRNA Vaccines to Prevent COVID-19 Disease and Reported Allergic Reactions: Current Evidence and
Suggested Approach. J. Allergy Clin. Immunol. Pract. 2021, 9, 1423–1437. [CrossRef] [PubMed]
9. Risma, K.A.; Edwards, K.M.; Hummell, D.S.; Little, F.F.; Norton, A.E.; Stallings, A.;Wood, R.A.; Milner, J.D. Potential Mechanisms
of Anaphylaxis to COVID-19 mRNA Vaccines. J. Allergy Clin. Immunol. 2021, 147, 2075–2082. [CrossRef] [PubMed]
10. Mohamed, M.; Abu Lila, A.S.; Shimizu, T.; Alaaeldin, E.; Hussein, A.; Sarhan, H.A.; Szebeni, J.; Ishida, T. PEGylated liposomes:
Immunological responses. Sci. Technol. Adv. Mater. 2019, 20, 710–724. [CrossRef] [PubMed]
11. Finkelman, F.D.; Khodoun, M.V.; Strait, R. Human IgE-independent systemic anaphylaxis. J. Allergy Clin. Immunol. 2016, 137,
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12. Hong, L.;Wang, Z.;Wei, X.; Shi, J.; Li, C. Antibodies against polyethylene
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