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Publications

Summary of the Public Assessment Report for COVID-19 Vaccine Pfizer/BioNTech – GOV.UK

The absence of reproductive toxicity data is a reflection of the speed of development to first identify and select COVID-19 mRNA Vaccine BNT162b2 for clinical testing and its rapid development to meet the ongoing urgent health need. In principle, a decision on licensing a vaccine could be taken in these circumstances without data from reproductive toxicity studies animals, but there are studies ongoing and these will be provided when available. In the context of supply under Regulation 174, it is considered that sufficient reassurance of safe use of the vaccine in pregnant women cannot be provided at the present time: however, use in women of childbearing potential could be supported provided healthcare professionals are advised to rule out known or suspected pregnancy prior to vaccination. Women who are breastfeeding should also not be vaccinated. These judgements reflect the absence of data at the present time and do not reflect a specific finding of concern. Adequate advice with regard to women of childbearing potential, pregnant women and breastfeeding women has been provided in both the Information for UK Healthcare Professionals and the Information for UK recipients.

https://www.gov.uk/government/publications/regulatory-approval-of-pfizer-biontech-vaccine-for-covid-19/summary-public-assessment-report-for-pfizerbiontech-covid-19-vaccine

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Publications

4th Dose COVID mRNA Vaccines’ Immunogenicity & Efficacy Against Omicron VOC – medRxiv

RESULTS Of 1050 eligible HCW, 154 and 120 were enrolled to receive BNT162b2 and mRNA1273, respectively, and compared to 426 age-matched controls. Recipients of both vaccine types had a ∼9-10-fold increase in IgG and neutralizing titers within 2 weeks of vaccination and an 8-fold increase in live Omicron VOC neutralization, restoring titers to those measured after the third vaccine dose. Breakthrough infections were common, mostly very mild, yet, with high viral loads. Vaccine efficacy against infection was 30% (95%CI:-9% to 55%) and 11% (95%CI:-43% to +43%) for BNT162b2 and mRNA1273, respectively. Local and systemic adverse reactions were reported in 80% and 40%, respectively.

CONCLUSIONS The fourth COVID-19 mRNA dose restores antibody titers to peak post-third dose titers. Low efficacy in preventing mild or asymptomatic Omicron infections and the infectious potential of breakthrough cases raise the urgency of next generation vaccine development.

https://www.medrxiv.org/content/10.1101/2022.02.15.22270948v1.full-text

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Publications

Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021 – JAMA

Question  What is the risk of myocarditis after mRNA-based COVID-19 vaccination in the US?

Findings  In this descriptive study of 1626 cases of myocarditis in a national passive reporting system, the crude reporting rates within 7 days after vaccination exceeded the expected rates across multiple age and sex strata. The rates of myocarditis cases were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively).

Meaning  Based on passive surveillance reporting in the US, the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata and was highest after the second vaccination dose in adolescent males and young men.

http://archive.today/2022.08.24-225032/https://jamanetwork.com/journals/jama/fullarticle/2788346

Categories
Publications

Report provides references indicating that HEK293 cells were derived from an aborted fetus – The Niche

The following recent report provides references indicating that HEK293 cells were derived from an aborted fetus:

Sander Lee, T., Feeney, M.B., Schmainda, K. M., Sherley, J. L., and Prentice, D. A. (2020) “Human Fetal Tissue from Elective Abortions in Research and Medicine: Science, Ethics, and Law.” Issues in Law & Med 35, 3-61.

Footnote 81 in the article provides the following link:

https://wayback.archive-it.org/7993/20170404095417/https:/www.fda.gov/ohrms/
dockets/ac/01/transcripts/3750t1_01.pdf

This link provides a 2001 US-FDA Meeting Transcript of the FDA-CBER Vaccines and Related Biological Products Advisory Committee. It contains the testimony of scientist Alex J. van der Eb, Ph.D., who participated in the development of HEK293 cells. On page 81 of the transcript, when describing the derivation of HEK293 cells, which were a focus of the committee meeting, Dr. van der Eb states:

“So the kidney material, the fetal kidney material was as follows. The kidney of the fetus was, with an unknown family history, was obtained in 1972 probably. The precise date is not known anymore. The fetus, as far as I can remember was completely normal. Nothing was wrong. The reasons for the abortion were unknown to me. I probably knew it at that time, but it got lost, all this information.”

https://archive.ph/Ho1vV#comment-44067

https://wayback.archive-it.org/7993/20170404095417/https:/www.fda.gov/ohrms/dockets/ac/01/transcripts/3750t1_01.pdf

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Publications

Explainer on 293 or HEK cells and their use in COVID vaccines – The Niche

What’s the deal with 293 cells and COVID-19 vaccine production?

There has been a lot of confusion and even misinformation about 293 cells out there related to the pandemic.

Different types of 293 cells have been used in research on COVID-19 vaccines by different manufacturers, but there are no cells in the actual vaccines. Some have gotten that wrong.

Also, 293s are not stem cells and, more specifically, are quite different from human embryonic stem cells. This has also often been an area of confusion.

What about at the ethical or moral level? I personally see no problem in vaccine research and production using 293 or other human cells.

The uncertainty over the origin of the fetus used to make 293 cells leaves things a little fuzzy in that regard, but I’d said it also makes it harder to somehow condemn 293 cells as immoral to use in research, if that’s one’s agenda.

http://archive.today/2022.07.01-165654/https://ipscell.com/2021/12/293-cells/

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Publications

Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel – The New England Journal of Medicine

Background
Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance.

Conclusions
The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.

http://archive.today/2021.10.10-032642/https://www.nejm.org/doi/full/10.1056/NEJMoa2109730

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News

Here are the facts about fetal cell lines and COVID-19 vaccines – National Geographic

In the wake of federal vaccine mandates in the U.S., debate has erupted over the waves of fire fighters,police staff, and other workers who have applied for religious exemptions to getting their COVID-19 shots. The number of applications is likely to spike as the January 4 vaccination deadline nears for large private businesses and some healthcare facilities. And one common reason people give for religious exemptions is the link between vaccines and human fetal cells.

It’s true that such cells have been used either in the testing or development and production of COVID-19 vaccines. The cells are grown in a laboratory and were derived from a few elective abortions performed more than three decades ago. These same cell lines are also used to test and advance our understanding of several routine drugs, including acetaminophen, ibuprofen, and aspirin, and they continue to be used for treatment research in diseases such as Alzheimer’s and hypertension.

http://archive.today/2022.01.28-071320/https://www.nationalgeographic.com/science/article/here-are-the-facts-about-fetal-cell-lines-and-covid-19-vaccines

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Publications

November 8, 2021 Summary Basis for Regulatory Action – Comirnaty – FDA

Introduction

BioNTech Manufacturing GmbH (in partnership with Pfizer Inc.) submitted a Biologics License Application (BLA) STN BL 125742 for licensure of COVID-19 Vaccine, mRNA. The proprietary name of the vaccine is COMIRNATY. COMIRNATY is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 16 years of age and older. The vaccine is administered intramuscularly (IM) as a series of two 30 μg doses (0.3 mL each) 3 weeks apart.

For commentary, see FDA report finds all-cause mortality higher among vaccinated – Israel Nation News.

http://archive.today/2021.10.11-032110/https://www.fda.gov/media/151733/download

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Publications

Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections – medRxiv

This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.

https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v1

Categories
Videos

Dr David Bauer: ‘Pfizer vaccine produces fewer key antibodies’ – MSN News

Dr Bauer of the Francis Crick Institute explains that the Pfizer vaccine produces 5-6 times fewer neutralising antibodies that play a key role in protecting us from the Indian variant. He suggests that booster Pfizer jabs will be essential.

https://www.msn.com/en-gb/news/other/dr-david-bauer-pfizer-vaccine-produces-fewer-key-antibodies/vi-AAKHPO1

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Publications

Pfizer-BioNTech vaccine recipients have lower antibody levels targeting the Delta variant first discovered in India – The Francis Crick Institute

Levels of antibodies in the blood of vaccinated people that are able to recognise and fight the new SARS-CoV-2 Delta variant first discovered in India (B.1.617.2) are on average lower than those against previously circulating variants in the UK, according to new laboratory data from the Francis Crick Institute and the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre, published today (Thursday) as a Research letter in The Lancet.

The results also show that levels of these antibodies are lower with increasing age and that levels decline over time, providing additional evidence in support of plans to deliver a vaccination boost to vulnerable people in the Autumn. 

https://www.crick.ac.uk/news/2021-06-03_pfizer-biontech-vaccine-recipients-have-lower-antibody-levels-targeting-the-delta-variant-first-discovered-in-india

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Publications

Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination – The Lancet

In the case of single-dose recipients, our data show that NAbTs are significantly lower against B.1.617.2 and B.1.351 VOCs relative to B.1.1.7, implying that although a single dose might still afford considerably more protection than no vaccination, single-dose recipients are likely to be less protected against these SARS-CoV-2 variants. These data therefore suggest that the benefits of delaying the second dose, in terms of wider population coverage and increased individual NAbTs after the second dose,7 must now be weighed against decreased efficacy in the short-term, in the context of the spread of B.1.617.2. Worldwide, our data highlight the ongoing need to increase vaccine supply to allow all countries to extend second-dose protection as quickly as possible.

In the longer term, we note that both increased age and time since the second dose of BNT162b2 significantly correlate with decreased NAb activity against B.1.617.2 and B.1.351—both of which are also characteristic of the population in the UK at highest risk of severe COVID-19 (ie, older and vaccinated earlier), independent of other existing factors such as compromised immune status or comorbidity, or geographic-specific responses to vaccination.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01290-3/fulltext

Categories
Publications

COVID-19 Vaccine Candidates and Abortion-Derived Cell Lines – Charlotte Lozier Institute

Accurate information about the development and production of COVID-19 vaccines is essential, especially because many proposed candidates use newer molecular technologies for production of a viral vaccine. One concern regarding the ethical assessment of viral vaccine candidates is the potential use of abortion-derived cell lines in the development, production or testing of a vaccine. This analysis utilizes data from the primary scientific literature when available, along with data from clinical trial documents, reputable vaccine tracking websites, and published commercial information.1 It is the hope that by providing accurate data, recipients can make well-informed decisions regarding vaccine choices.

Analysis of SARS-CoV-2 (COVID-19) Vaccine Candidates

Last Updated 2 June 2021

 

🟩 DOES NOT USE abortion-derived cell line

 

 

🔺 DOES USE abortion-derived cell line

 

 

🟩🔺 SOME tests DO NOT use abortion-derived cells, SOME DO.

 

Currently undetermined

Sponsor(s)1 Country Strategy2 Clinical Trial Status3 Public Funding4 Design & Development Production Confirm-atory
Lab Tests
WHOLE VIRUS VACCINE – LIVE ATTENUATED or INACTIVATED
Beijing Institute of Biological Products/ Sinopharm China Inactivated virus

“BBIBP-CorV”

Given: Intramuscular

2 doses (3 weeks apart)

WHO granted Emergency Use Listing (EUL) 7May2021

Early approval in China

Phase 3

Phase 3

🟩

Vero monkey cells

Wang et al., Cell 182, P713, 6Aug2020

 

🟩

Vero monkey cells

Wang et al., Cell 182, P713, 6Aug2020

 

🟩

Cytopathic test

Vero monkey cells

Wang et al., Cell 182, P713, 6Aug2020

Wuhan Institute of Biological Products/ Sinopharm China Inactivated virus

“New Crown COVID-19”

Given: Intramuscular

2 doses (3 weeks apart)

Phase 3

Phase 3

Phase 3

Early approval in China

Phase 1/2

🟩

Vero monkey cells
Xia et al., JAMA 324, 951, 13Aug2020

🟩

Vero monkey cells

Xia et al., JAMA 324, 951, 13Aug2020

🟩
Plaque reduction neutralization test
Vero monkey cells
Xia et al., JAMA 324, 951, 13Aug2020
Bharat Biotech/Indian Council of Medical Research India Inactivated virus
“BBV152”
Given: Intramuscular
2 doses (2 weeks apart)
India EUA granted

Phase 3

Phase 3

Phase 1/2

Phase 1/2

Phase 1/2

🟩

Vero monkey cells

Yadav et al., ResearchSquare 10Sept2020

🟩

Vero monkey cells

Yadav et al., ResearchSquare 10Sept2020

🟩
Antibody ELISA
Plaque reduction
Vero monkey cellsYadav et al., ResearchSquare 10Sept2020
Institute of Medical Biology, Chinese Academy of Medical Sciences China Inactivated virus
“SARS-CoV-2 vaccine”
Given: Intramuscular
2 doses (2 weeks apart)
Phase 3

Phase 1/2

Phase 1/2

🟩

Vero monkey cells

Pu et al., medRxiv, 6Oct2020

🟩

Vero monkey cells

Pu et al., medRxiv, 6Oct2020

🟩
Antibody ELISA
Neutralizing antibody cytopathic effect
Vero monkey cells
Pu et al., medRxiv, 6Oct2020
Supplement
John Paul II Medical Research Institute USA Live attenuated virus

 

Pre-clinical 🟩

Ethical cell lines as a matter of policy

🟩

Perinatal human cells (term umbilical cord and placental)

Research Institute for Biological Safety Problems Kazakhstan Inactivated virus

“QazCovid-in”

Given: Intramuscular

2 doses (3 weeks apart)

Phase 3

Phase 1/2

Sinovac Biotech Co., Ltd. China Inactivated virus

“CoronaVac”

Given: Intramuscular

2 doses (2 weeks apart)

 

WHO granted Emergency Use Listing (EUL) 1June2021

Phase 4

China granted conditional marketing authorization 8Feb2021
Chile, Brazil, Turkey, Indonesia EUA granted

Phase 3

Early approval in China

Phase 3

Phase 1/2

Phase 1/2

Phase 1/2

🟩

Vero monkey cells

 

🟩

Vero monkey cells

Gao et al., Science 369, 77, 3July2020

🟩🔺

protein test

HEK293 cells

Supplement Gao et al., Science 369, 77, 3July2020

Valneva and Dynavax France
USA
UK
Inactivated Virus
“VLA2001”
plus adjuvant CpG1018
Given: Intramuscular
2 doses (3 weeks apart)
Phase 3

Phase 1/2

🟩

Vero monkey cells

 

🟩

Vero monkey cells

Same platform as IXIARO, Valneva press release, 22April2020

Valneva COVID-19 – VLA2001

VIRAL VECTOR-BASED VACCINE
Altimmune USA Replication-deficient

Adenovirus vector

“AdCOVID”

Given: Intranasal
1-2 doses

Phase 1/2 🔺

PER.C6 cells

🔺

PER.C6 cells

Same platform as NasoVAX

NasoVAX uses PER.C6

Licensed PER.C6 from Janssen

🔺
AstraZeneca

University of Oxford

 

USA

UK

Replication-deficient

Adenovirus vector

“AZD1222”

“ChAdOX1nCoV-19”

Given: Intramuscular

2 doses (4 weeks apart)

WHO granted Emergency Use Listing (EUL) on 15Feb2021

UK EUA granted

India EUA granted

Phase 3

Phase 3

Phase 3

Phase 3

Phase 2/3

Phase 2/3

Phase 1/2

Phase 1/2

Operation Warp Speed

HHS-BARDA

$1.2 Billion

CEPI up to $384 Million

🔺

HEK293 cells

🔺

HEK293 cells

van Doremalen et al., Nature, 30July2020

🔺
HEK293 cellsvan Doremalen et al., Nature, 30July2020
MRC-5 cells
Almuqrin et al., ResearchSquare 20Oct2020
CanSino Biologics, Inc.

Beijing Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China

China Replication-deficient

Adenovirus vector

“Ad5-nCoV”

Given: Intramuscular

1 dose

EUA in Chile, Hungary, Pakistan, Mexico

Phase 3

Phase 3

Phase 2

Phase 2

Phase 2

Phase 1

Phase 1

🔺

HEK293 cells

🔺

HEK293 cells

Biospace, 12May2020

🔺
Gamaleya Research Institute Russia Replication-deficient

Adenovirus vectors

(rAd26-S+rAd5-S)

“Gam-COVID-Vac”

“Sputnik V”

Given: Intramuscular

2 doses (3 weeks apart)

Phase 3

Phase 3

EUA in 39 countries as of Mar2021

Early approval in Russia August 2020

Phase 1/2

Phase 1/2

🔺

HEK293 cells

🔺

HEK293 cells
Gamaleya has not published details on this vaccine, but has posted information on use of cell lines for their other adenoviral vaccines

🔺
ImmunityBio and NantKwest USA Replication-deficient Adenovirus vector recombinant
“hAd5 S-Fusion + N-ETSD”
Given: Subcutaneous
Phase 1/2

Phase 1/2

Phase 1
Phase 1
Phase 1

🔺
E.C7 cells
(derivative of HEK293 cells)
Rice et al., bioRxiv 30July2020
🔺

E.C7 cells
(derivative of HEK293 cells)
Rice et al., bioRxiv 30July2020

🔺
Protein and antibody tests
HEK293T cells
Rice et al., bioRxiv 30July2020
Seiling et al., medRxiv 6Nov2020
Institut Pasteur and Themis and Merck USA

France

Replication-competent recombinant measles virus

“TMV-083”

Given: Intramuscular

Development Discontinued
Phase 1/2Phase 1
CEPI up to $4.9 Million 🔺HEK293T

Development and rescue of recombinant measles virus

Hörner et al., PNAS 22Dec2020

Hörner et al. Supplement

“SARS-CoV-2 S-encoding vaccine candidates… were generated as described previously

 

🟩

Vero monkey cells

Hörner et al., PNAS 22Dec2020

Hörner et al. Supplement

🟩🔺
Lentiviral vectors for antigenic DCFusogenic testHEK293TFusogenic testS protein expressionVero monkey cellsHörner et al., PNAS 22Dec2020Hörner et al. Supplement
Israel Institute for Biological Research (IIBR) Israel Replication-competent recombinant vesicular stomatitis virus (VSVΔG)
“IIBR-100”
Given: Intramuscular1 dose
Phase 1/2 🟩
BHK hamster cells
Vero monkey cells
Yahalom-Ronen et al., bioRxiv 19June2020
🟩
Vero monkey cells
Yahalom-Ronen et al., bioRxiv 19June2020
🟩
Plaque reduction; immunofluorescence
Vero monkey cells
Yahalom-Ronen et al., bioRxiv 19June2020
Janssen Research & Development, Inc.

Johnson & Johnson

USA Replication-deficient

Adenovirus vector

“Ad26.COV2-S”
Given: Intramuscular

1 dose
(some trials use 2 doses, 8 weeks apart)

FDA Emergency Use Authorization Approved

Phase 3

Phase 3

Phase 1/2

Operation Warp Speed

HHS-BARDA

$1,457,887,081 total

🔺

PER.C6 cells

🔺

PER.C6 cells

Tostanoski et al., Nature Medicine, 3Sept2020;

J&J, 30March2020;

Janssen Vaccine Technologies

🔺
Laboratorio Avi-Mex Mexico Live recombinant Newcastle Disease Virus

Expressing spike-fusion chimeric protein

“Patria”

Given: Intramuscular or Intranasal

Phase 1 🟩

Bacterial cells

BSRT7 hamster cells

Per Sun et al., Vaccines 17Dec2020

🟩

Chicken eggs

Per Sun et al., Vaccines 17Dec2020

🟩

Neutralization Assay

Vero monkey cells

Per Sun et al., Vaccines 17Dec2020

Meissa Vaccines, Inc. USA Live attenuated recombinant RSV viral vector

“MV-014-210”

Given: Intranasal

1-3 doses (5 weeks apart)

Phase 1 🟩 🟩

Vero monkey cells

Spike expressing,

Based on recombinant RSV platform

Rega Institute, KU Leuven Belgium Replication-competent attenuated yellow fever vaccine (YF17D) vector

“YF-S0”

Given: Intramuscular
1 dose

Pre-clinical 🟩

BHK-21J hamster cells
Sanchez-Felipe et al., Nature, 1Dec2020

🟩

BHK-21J hamster cells
Sanchez-Felipe et al., Nature, 1Dec2020

🟩🔺
Antibody titer
Pseudovirus
HEK293T cells
Immunoblot
BHK-21J hamster cells
Sanchez-Felipe et al., Nature, 1Dec2020
ReiThera Italy Replication-deficient simian adenovirus encoding S

“GRAd COV2”

Given: Intramuscular

1 dose

Phase 2/3

Phase 1

🔺

HEK293T cells

Development and rescue of recombinant

Capone et al., bioRxiv 22Oct2020

🔺

HEK293T cells

Capone et al., bioRxiv 22Oct2020

🔺

HEK293T cells

Capone et al., bioRxiv 22Oct2020

Merck and IAVI USA Replication-competent recombinant vesicular stomatitis virus (VSVΔG)

“V590”

Given: Intramuscular

Development Discontinued
Phase 1
Operation Warp Speed

HHS-BARDA

$38,033,570

🟩

Vero monkey cells

🟩

Vero monkey cells

Use rVSV Ervebo platform

Ervebo uses Vero cell culture-11 Description

Shenzhen Geno-immune

Medical Institute

China Lentivirus minigenes +

Adult human APC (antigen-presenting cells)

“COVID-19/aAPC”

Given: Subcutaneous

3 doses (2 weeks apart)

Phase 1 🟩
Shenzhen Geno-immune

Medical Institute

China Lentivirus minigenes +

Adult human CD/T cells (dendritic cells and T cells)

“LV-SMENP-DC”

Given: Subcutaneous and Intravenous

1 dose

Phase 1/2 🟩
Vaxart USA Replication-deficient

Adenovirus vector

“VXA-CoV2-1”

plus dsRNA adjuvant

Given: Oral

2 doses (4 weeks apart)

Phase 1 🔺

HEK293 cells

🔺

HEK293 cells

Moore et al., bioRxiv 6Sept2020

🔺
PROTEIN-BASED VACCINE
Anhui Zhifei Longcom Biopharmaceutical/Institute of Microbiology, Chinese Academy of Sciences China Protein vaccine

Recombinant RBD dimer

plus adjuvant

”ZF2001”

Given: Intramuscular

2 or 3 doses (28 days apart)

Phase 3

Phase 2

Phase 1/2

Phase 1

🔺

HEK293T cells

Dai et al., Cell 6Aug2020

🟩

CHO hamster cells

Dai et al., Cell 6Aug2020

🔺

Pseudovirus

HEK293T cells

Dai et al., Cell 6Aug2020

Clover Biopharmaceuticals, Inc. China Protein vaccine

“SCB-2019”

plus adjuvant CpG 1018

Given: Intramuscular
2 doses (3 weeks apart)

Phase 2/3

Phase 1

CEPI up to $69.5 Million 🟩cDNA in expression vector; transfect CHO hamster cells

Liang et al., bioRxiv, 24Sept2020

Trimer-Tag system;

Liu et al., Scientific Reports 2017

🟩

CHO hamster cells

Trimer-Tag system;

Liu et al., Scientific Reports 2017

🟩🔺
PseudovirusHEK293 cellsRef’d: Nie et al., Emerging Microbes & Infections 24Mar2020Cytopathic effect Vero monkey cellsLiang et al., bioRxiv, 24Sept2020
COVAXX and United Biomedical USA
Taiwan
Protein vaccine

“UB-612”

S1-RBD-protein; Multitope Peptide-Based Vaccine (MVP)

Given: Intramuscular
2 doses (4 weeks apart)

Phase 2/3

Phase 1

🟩cDNA in expression vector; transfect CHO hamster cells

Guirakhoo et al., bioRxiv, 30Nov2020

🟩

CHO hamster cells
Guirakhoo et al., bioRxiv, 30Nov2020

🟩🔺
Antibody blocked binding to hACE2 HEK293
Guirakhoo et al., bioRxiv, 30Nov2020
Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vektor” Russia Protein vaccine
“EpiVacCorona”
chemically synthesized peptide antigens of SARS-CoV-2, conjugated to a carrier protein
adsorbed on an aluminum-containing adjuvant
Given: Intramuscular2 doses (3 weeks apart)
Phase 3

Early approval in Russia Oct 2020

Phase 1/2

🟩

chemically synthesized peptide antigens

Instituto Finlay de Vacunas Cuba Protein vaccine
“Finlay-FR-1”
(“Soberana 01”)
Receptor-binding domain (RBD) SARS-CoV-2 spike + adjuvant
Given: Intramuscular2 doses (4 weeks apart)
Phase 1/2
Phase 1

RBD produced in mammalian cells
Garcia-Rivera, MEDICC Review, 30Oct2020

RBD produced in mammalian cells
Garcia-Rivera, MEDICC Review, 30Oct2020
Instituto Finlay de Vacunas Cuba Protein vaccine
“Finlay-FR-2”
(“Soberana 02”)
Receptor-binding domain (RBD) SARS-CoV-2 spike chemically bound tetanus toxoid + adjuvant
Given: Intramuscular2 doses (4 weeks apart)
Phase 2
Phase 1

RBD produced in mammalian cells
Garcia-Rivera, MEDICC Review, 30Oct2020

RBD produced in mammalian cells
Garcia-Rivera, MEDICC Review, 30Oct2020
John Paul II Medical Research Institute USA Recombinant Protein

Perinatal human cells (term umbilical cord and placental)

Pre-clinical 🟩

Ethical cell lines as a matter of policy

🟩

Perinatal human cells (term umbilical cord and placental)

Kentucky BioProcessing, Inc.
(British American Tobacco)
USA Protein vaccine
“KBP-201”
Plant-expressed RBD
Given: Intramuscular2 doses (3 weeks apart)
Phase 1/2 🟩

Recombinant DNA sequence for RBD of SARS-CoV-2

🟩

Plant expression of RBD peptide

Medicago Canada Protein on Virus-Like Particle

“CoVLP”

Plant-expressed spike protein particle with adjuvant, CpG1018 or AS03

Given: Intramuscular

2 doses (3 weeks apart)

Phase 2/3

Phase 2

Phase 1

🟩

Recombinant DNA sequence in Agrobacterium, transformation of plant cells

🟩

Plant expression of protein and VLP

Ward et al., medRxiv 6Nov2020

🟩🔺

Pseudovirus

HEK293 cells

Ward et al., medRxiv 6Nov2020

Migal Galilee Research Institute Israel Protein vaccine

E. coli expressed chimeric S and N proteins

Given: Oral

Pre-clinical 🟩

Bacterial production system

MigVax’s corona subunit vaccine

Novavax USA Protein vaccine

“NVX-CoV2373”

Baculovirus expression

plus Matrix M adjuvant

Given: Intramuscular

2 doses (3 weeks apart)

Phase 3

Phase 3

Phase 2

Phase 1

Operation Warp Speed

HHS-BARDA

$1,600,434,523

CEPI up to $388 Million

🟩 🟩

Sf9 insect cells
Bangaru et al., Science, 27Nov2020
Bangaru et al., Supplement
Bangaru et al., bioRxiv preprint, 6Aug2020;

Graphical view

🟩🔺

Pseudovirus

HEK293 cells
Bangaru et al., Science, 27Nov2020
Bangaru et al., Supplement
Bangaru et al., bioRxiv preprint, 6Aug2020

Sanofi and GSK

Protein Sciences

 

USA

France

Protein vaccine

Baculovirus expression

plus AS03 adjuvant

Given: Intramuscular

2 doses (3 weeks apart)

Phase 3

Phase 2

Phase 1/2

Operation Warp Speed

HHS-BARDA

$2,072,775,336 total

🟩

Recombinant baculovirus

Francica et al., bioRxiv 2Mar2021

🟩

Sf9 insect cells

Francica et al., bioRxiv 2Mar2021

Baculovirus expressed recombinant protein

🟩🔺

Pseudovirus

HEK293T cells

Francica et al., bioRxiv 2Mar2021

Sorrento USA Protein vaccine

“T-VIVA-19”

SARS-Cov-2 spike protein S1 domain fused with human IgG-Fc

Given: Intramuscular

Pre-clinical 🟩 🟩

CHO cells

Herrmann et al., bioRxiv preprint, 30June2020

🟩

Antibody ELISA;

Neutralization assays

Vero monkey cells

Herrmann et al., bioRxiv preprint, 30June2020

Sorrento USA Protein vaccine

“STI-6991”

SARS-Cov-2 spike protein expressed on K562 cells

Pre-clinical 🟩

K562 cells

Concept: Ji et al., Medicine in Drug Discovery March2020

University of Pittsburgh USA Protein vaccine

Adenovirus-expressed

recombinant proteins

“PittCoVacc”

Given: Microneedle arrays

Pre-clinical 🔺

HEK293 cells

🔺

HEK293 cells

Kim et al., EBioMedicine , 2April2020

🔺
University of Queensland and CSL Ltd. Australia Protein vaccine

“V451”

Recombinant protein with proprietary molecular clamp

Given: Intramuscular

HALTED

Phase 1

Phase 1

Phase 1

CEPI up to $4.5 Million 🟩 🟩

expiCHO hamster cells

 

Walter Reed Army Institute of Research (WRAIR) / U.S. Army Medical Research and Development Command USA Protein vaccine

”SpFN”

Spike-Ferritin nanoparticle with ALFQ adjuvant

Given: Intramuscular

2-3 doses (4 weeks apart; plus 6 months after initial injection)

Phase 1 🔺

Expi293 cells

Carmen et al., bioRxiv 28April2021

🔺

Expi293 cells

Carmen et al., bioRxiv 28April2021

🟩🔺

Pseudovirus

HEK293 cells

Virus neutralization

Vero monkey cells

Joyce et al., bioRxiv 25Mar2021

& Supplement

RNA VACCINE
Arcturus Therapeutics USA mRNA vaccine

self-transcribing, replicating

“LUNAR-CoV19” (“ARCT-021”)

in vitro transcription reaction with T7 RNA polymerase from STARR plasmid template

LUNAR proprietary lipid nanoparticle encapsulated

Given: Intramuscular

1 dose

Phase 2

Phase 2

 

Phase 1/2

🟩

Sequence designed on computer

🟩

No cells used

de Alwis et al., bioRxiv 3Sept2020

🟩🔺

protein test

HEK293

Protein expression

Hep3b cells

Plaque reduction neutralization

Vero monkey cells

de Alwis et al., bioRxiv 3Sept2020

CureVac Germany mRNA vaccine

non-replicating

“CVnCoV”

in vitro transcription

lipid nanoparticle encapsulated

Given: Intramuscular

2 doses (4 weeks apart)

Phase 3

Phase 2/3

Phase 2

Phase 1

CEPI up to $15.3 Million 🟩

Sequence designed on computer

🟩

No cells used

Rauch et al., bioRxiv 9Feb2021

🟩

Protein test

Reticulocyte lysate,
HeLa cells

Rauch et al., bioRxiv 9Feb2021

Imperial College London UK mRNA vaccine

Self-amplifying

”LNP-nCoVsaRNA”

in vitro transcription

lipid nanoparticle encapsulated

Given: Intramuscular

2 doses

Phase 1 🔺

Expression plasmid

HEK293 cells

McKay et al., bioRxiv 25April2021

🟩

No cells used

McKay et al., bioRxiv 25April2021

🟩🔺

Pseudovirus

HEK293T cells

McKay et al., bioRxiv 25April2021

Moderna, Inc.

with National Institutes of Health

USA mRNA vaccine

non-replicating

“mRNA-1273”

T7 RNA polymerase-mediated transcription from DNA plasmid template

LNP (lipid nanoparticle) encapsulated

Given: Intramuscular

2 doses (4 weeks apart)

FDA Emergency Use Authorization Approved

Phase 3

Phase 2

Phase 1

Operation Warp Speed

HHS-BARDA

$2,479,894,979 total

CEPI up to $1 Million

 

🟩

Sequence designed on computer

🟩

No cells used

Corbett et al., Nature , 5Aug2020

🟩🔺

protein test

& pseudovirus

HEK293 cells

Plaque reduction neutralization

Vero monkey cells

Corbett et al., Nature , 5Aug2020

Pfizer and BioNTech USA

Germany

mRNA vaccine

non-replicating

“BNT-162a1,b1,b2,b3,c2”

nucleoside-modified mRNA in vitro transcribed by T7 polymerase from a plasmid DNA template

LNP (lipid nanoparticle) encapsulated

Given: Intramuscular

2 doses (3 weeks apart)

FDA Emergency Use Authorization Approved

UK EUA granted

Phase 2/3

Phase 1/2

Phase 1/2

Phase 1

Phase 1

 

Operation Warp Speed

HHS-BARDA

$1.95 Billion

🟩

Sequence designed on computer

🟩

No cells used

Vogel et al., bioRxiv 8Sept2020

🟩🔺

protein test

& pseudovirus

HEK293 cells

Neutralization assay

Vero monkey cells

Vogel et al., bioRxiv 8Sept2020

Providence Therapeutics Canada mRNA vaccine

“PTX-COVID19-B”

mRNA in vitro transcription from plasmid template using T7 RNA polymerase
LNP (lipid nanoparticle) encapsulated

Given: Intramuscular

2 doses (4 weeks apart)

Phase 1 🔺

HEK293T cells used to select mRNA candidate

Liu et al., bioRxiv 12May2021

🟩

No cells used

Cision, 5Aug2020
Providence Therapeutics

Liu et al., bioRxiv 12May2021

🟩🔺

Pseudovirus, serum neutralization

HEK293T cells

Vero monkey cells

Liu et al., bioRxiv 12May2021

Sanofi Pasteur and

Translate Bio

USA

France

mRNA vaccine

non-replicating

“MRT5500”

synthesized by in vitro transcription employing RNA polymerase with a plasmid DNA template

LNP (lipid nanoparticle) encapsulated

Given: Intramuscular

2 doses (3 weeks apart)

Phase 1/2 🔺

HEK293T cells used to select mRNA candidate

Kalnin et al., npj Vaccines 19Apr2021

🟩

No cells used

Kalnin et al., npj Vaccines 19Apr2021

Kalnin et al., bioRxiv 14Oct2020

mRNA production in the lab ;

Translate Bio scientific platform

🟩🔺

protein test

& pseudovirus

HEK293 cells

Kalnin et al., npj Vaccines 19Apr2021

Kalnin et al., bioRxiv 14Oct2020

DNA VACCINE
Genexine Korea DNA vaccine

“GX-19”

DNA synthesized in vitro, placed in plasmid vector

Given: Intramuscular and Electroporation

2 doses (4 weeks apart)

Phase 1/2

Phase 1/2

🟩

Sequence designed on computer

🟩

No cells used

Seo et al., Vaccines 24March2021

🟩No cells used

Seo et al., Vaccines 24March2021

Inovio Pharmaceuticals USA DNA vaccine

“INO-4800”

DNA synthesized in vitro, placed in plasmid vector

Given: Intradermal Electroporation

2 doses (4 weeks apart)

Phase 2/3

Phase 2

Phase 1/2

Phase 1

Operation Warp Speed

CEPI up to $22.5 Million

🟩

Sequence designed on computer

🟩

No cells used

Smith et al., Nature 20May2020

🟩🔺

protein test

& pseudovirus

HEK293 cells

Smith et al., Nature 20May2020

Osaka University, AnGes, Takara Bio Japan DNA vaccine

“AG0301-COVID19”
“AG0302-COVID19”
Chemically synthesized plasmid vector grown in E. coli
Pressure injector
Given: Intramuscular

2 doses (2 weeks apart)

Phase 2/3

Phase 1/2

Phase 1/2

🟩

Sequence designed on computer

🟩

No cells used
E. coli</em
Nishikawa et al., bioRxiv, 14Jan2021

🟩

Virus neutralization

Vero E6 cells monkey cells
Nishikawa et al., bioRxiv, 14Jan2021

Symvivo Corporation Canada DNA vaccine

“bacTRL-spike”
Genetically engineered Bifidobacterium longum

Given: Oral, bacteria bind to gut lining

1 dose

Phase 1 🟩

No cells used

Zydus Cadila India DNA vaccine

“ZyCov-D”
Chemically synthesized plasmid vector grown in E. coli
Given: Intramuscular

3 doses (4 weeks apart)

Phase 3

Phase 1/2

🟩

Sequence designed on computer

🟩

No eukaryotic cells used
E. coli</em
Dey et al., bioRxiv, 26Jan2021

🟩

Expression analysis
Plaque reduction
Vero cells monkey cells
Dey et al., bioRxiv, 26Jan2021
Yadav et al., bioRxiv, 3Feb2021

http://archive.today/2022.06.16-202534/https://lozierinstitute.org/update-covid-19-vaccine-candidates-and-abortion-derived-cell-lines/

Categories
Publications

First case of postmortem study in a patient vaccinated against SARS-CoV-2 – NCBI

A previously symptomless 86-year-old man received the first dose of the BNT162b2 mRNA COVID-19 vaccine. He died 4 weeks later from acute renal and respiratory failure. Although he did not present with any COVID-19-specific symptoms, he tested positive for SARS-CoV-2 before he died. Spike protein (S1) antigen-binding showed significant levels for immunoglobulin (Ig) G, while nucleocapsid IgG/IgM was not elicited. Acute bronchopneumonia and tubular failure were assigned as the cause of death at autopsy; however, we did not observe any characteristic morphological features of COVID-19. Postmortem molecular mapping by real-time polymerase chain reaction revealed relevant SARS-CoV-2 cycle threshold values in all organs examined (oropharynx, olfactory mucosa, trachea, lungs, heart, kidney and cerebrum) except for the liver and olfactory bulb. These results might suggest that the first vaccination induces immunogenicity but not sterile immunity.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051011/

Categories
News

Cells from human foetuses are important for developing vaccines – but they’re not an ingredient – The Conversation

Two embryonic cell lines have been used to develop COVID-19 vaccines: human embryonic kidney cells called HEK 293 and human embryonic retinal cells called PER.C6. The PER.C6 cell line is from an elective abortion in the Netherlands in 1985, and the HEK 293 cell line comes from an undisclosed source (either spontaneous miscarriage or elective abortion) in the Netherlands in about 1972.

Johnson & Johnson used PER.C6 cells in their COVID-19 vaccine development, and the Oxford/AstraZeneca vaccine used HEK 293 cells. CanSino Biologics and Gamaleya Research Institute’s Sputnik V vaccines have also used HEK 293 cells.

Moderna and Pfizer/BioNTech used HEK 293 cells in their proof-of-concept tests to see effectively take up the genetic instructions contained in these vaccines and produce the required spike protein. But human embryonic cell lines were not used to make either company’s final vaccine.

HEK 293 and PER.C6 cell lines have been genetically altered to include the part of the adenovirus instructions that trigger replication of adenoviruses. This allows the production of a large amount of the final vaccination product and allows the removal of the adenoviral replication instructions in the vaccine.

http://archive.today/2022.10.02-145609/https://theconversation.com/cells-from-human-foetuses-are-important-for-developing-vaccines-but-theyre-not-an-ingredient-157484

Categories
Publications

Outcome Reporting Bias in COVID-19 mRNA Vaccine Clinical Trials – NCBI

Abstract
Relative risk reduction and absolute risk reduction measures in the evaluation of clinical trial data are poorly understood by health professionals and the public. The absence of reported absolute risk reduction in COVID-19 vaccine clinical trials can lead to outcome reporting bias that affects the interpretation of vaccine efficacy. The present article uses clinical epidemiologic tools to critically appraise reports of efficacy in Pfzier/BioNTech and Moderna COVID-19 mRNA vaccine clinical trials. Based on data reported by the manufacturer for Pfzier/BioNTech vaccine BNT162b2, this critical appraisal shows: relative risk reduction, 95.1%; 95% CI, 90.0% to 97.6%; p = 0.016; absolute risk reduction, 0.7%; 95% CI, 0.59% to 0.83%; p < 0.000. For the Moderna vaccine mRNA-1273, the appraisal shows: relative risk reduction, 94.1%; 95% CI, 89.1% to 96.8%; p = 0.004; absolute risk reduction, 1.1%; 95% CI, 0.97% to 1.32%; p < 0.000. Unreported absolute risk reduction measures of 0.7% and 1.1% for the Pfzier/BioNTech and Moderna vaccines, respectively, are very much lower than the reported relative risk reduction measures. Reporting absolute risk reduction measures is essential to prevent outcome reporting bias in evaluation of COVID-19 vaccine efficacy.

Conclusions
A critical appraisal of phase III clinical trial data for the Pfizer/BioNTech vaccine BNT162b2 and Moderna vaccine mRNA-1273 shows that absolute risk reduction measures are very much lower than the reported relative risk reduction measures. Yet, the manufacturers failed to report absolute risk reduction measures in publicly released documents. As well, the U.S FDA Advisory Committee (VRBPAC) did not follow FDA published guidelines for communicating risks and benefits to the public, and the committee failed to report absolute risk reduction measures in authorizing the BNT162b2 and mRNA-1273 vaccines for emergency use. Such examples of outcome reporting bias mislead and distort the public’s interpretation of COVID-19 mRNA vaccine efficacy and violate the ethical and legal obligations of informed consent.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996517/