thevaccinereaction--2020-05-04--GSK and Sanofi COVID-19 Vaccine Produced in Insect Cells with Squalene Adjuvant

On Apr .
14 , 2020 , GlaxoSmithKline ( GSK ) of the United Kingdom and Sanofi Pasteur of France announced they have signed a letter of intent to collaborate on development of an experimental COVID-19 vaccine using existing technology patented by both companies.1 According to GSK ’ s chief executive Emma Walmsley , “ This collaboration brings two of the world ’ s largest vaccines companies together .
By combining our science and our technologies , we believe we can help accelerate the global effort to develop a vaccine to protect as many people as possible from COVID-19.
” @ @ @ @ @ @ @ COVID-19 vaccine in collaboration with and $ 30M in funding from the U.S. government ’ s Biomedical Advanced Research and Development Authority ( BARDA ) 2 under the HHS Office of the Assistant Secretary for Preparedness and Response .
The experimental coronoavirus vaccine will combine GSK ’ s proprietary squalene-based vaccine adjuvant AS03 used in the company ’ s H1N1 influenza vaccine Pandemrix , with the insect cell-based recombinant DNA vaccine technology that Sanofi Pasteur currently uses to make their inactivated quadrivalent influenza vaccine , FluBlok .
GSK is the largest pharmaceutical company @ @ @ @ @ @ @ is the third largest .
According to Scrip Informa Pharma Intelligence , the business partnership between the two experienced vaccine manufacturers utilizing already licensed technology to create a COVID-19 vaccine could place them in front of companies seeking approval for experimental mRNA and DNA technology not yet licensed:3 Adjuvants are added to vaccines to enhance the pro-inflammatory immune response induced by vaccination.4 Aluminum salts were added to the diphtheria-tetanus toxoid vaccines in the 1920 ’ s and remained as an ingredient when whole cell pertussis vaccine was added to create the combination DPT @ @ @ @ @ @ @ when the acellular pertussis vaccine ( DTaP ) vaccine was licensed for infants in 1996 .
Aluminum-based adjuvants are included in hepatitis , HPV , pneumococcal , meningococcal and other inactivated vaccines routinely administered to children and adults , as well as in anthrax vaccine given to US military personnel.5 Evidence that aluminum is neurotoxic to humans has been steadily accumulating in the medical literature.6 7 An oil-based vaccine adjuvant was introduced in the U.S. in 2007 , when GSK ’ s HPV vaccine , Cervarix , was licensed and contained monophosphoryl lipid @ @ @ @ @ @ @ hydroxide ( Cervarix is no longer available in the U.S. ) .8 In 2012 , the FDA licensed an H5N1 influenza vaccine containing GSK ’ s oil-based AS03 adjuvant and the vaccine was added to the national stockpile for emergency use if there is an outbreak of H5N1 bird flu.9 In 2015 , the FDA licensed an influenza vaccine ( Fluad ) manufactured by Sequiris for seniors over age 65 years that contains an oil-in-water emulsion of squalene oil ( MF59 ) as an adjuvant.10 11 AS03 is GSK ’ s proprietary adjuvant @ @ @ @ @ @ @ oil-in-water emulsion.12 AS03 ramps up the pro-inflammatory immune response in the body to try to generate cellular immunity and more vaccine strain antibodies .
Adding AS03 to a vaccine also makes it easier for a company to manufacture a vaccine in large quantities.13 If the FDA licenses a COVID-19 vaccine containing ASO3 , it would be the first time a vaccine recommended for all children and adults in the U.S. would contain an oil-based adjuvant .
GSK ’ s 2009/2010 H1N1 influenza vaccine , Pandemrix , contained the company ’ s AS03 adjuvant @ @ @ @ @ @ @ U.S. but , after it was used in 2009-2010 in Europe , there were reports that a number of children in Norway , Finland , the UK and other countries developed narcolepsy , an autoimmune disorder.14 By 2013 , studies conducted in Europe had confirmed an association between the AS03-adjuvanted Pandemrix vaccine and narcolepsy.15 16 In response , GSK scientists published a study in 2019 defending the safety of AS03.17 There are continuing reports in the medical literature that children and adults with certain genotypes are more susceptible to developing autoimmune disorders after @ @ @ @ @ @ @ increased risks for individuals unable to resolve strong pro-inflammatory responses stimulated by oil-based adjuvants like AS03.18 19 In 2018 , scientists working for GSK commented in an article for Seminars in Immunology that there are significant knowledge gaps about the molecular mechanisms for how vaccine adjuvants affect immune function:20 The GSK scientists acknowledged that oil adjuvanted vaccines increase the inflammatory response to increase immunogenicity , while also increasing reactogenicity , and the biological mechanisms for adverse reactions and the genetic risk factors involved are not understood : Sanofi Pasteur will contribute its S-protein @ @ @ @ @ @ @ recombinant DNA technology , for the experimental coronovirus vaccine .
According to the joint press release issued by GSK and Sanofi on Apr .
14 , “ This technology has produced an exact genetic match to proteins found on the surface of the virus , and the DNA sequence encoding this antigen has been combined into the DNA of the baculovirus expression platform , the basis of Sanofi ’ s licensed recombinant influenza product in the US.
” 1 Sanofi ’ s recombinant FluBlok influenza vaccine was originally developed by Protein Sciences , @ @ @ @ @ @ @ in 2017.21 In 2013 , the FDA licensed trivalent FluBlok influenza vaccine and , in 2017 , quadrivalent FluBlok was licensed.22 In 2012 , a year before the FDA gave Protein Sciences a license to market FluBlok in the U.S. , a scientist working for Protein Sciences explained the “ plug and play ” benefits of using the Baculovirus Expression Vector System ( BEVS ) for vaccine production:23 Sanofi ’ s FluBlok contains hemagglutinen ( HA ) genes from influenza viruses produced in ovarian cells from the Fall Army Worm ( Spodopter frugperda @ @ @ @ @ @ @ Canadian bioengineers described the 45-day process it takes to produce FluBlok vaccine:26 According to the National Institutes of Health , the recombinant DNA technology that Sanofi uses to produce their FluBlok influenza vaccine ( and will be used to produce the GSk/Sanofi COVID-19 vaccine ) will likely eventually replace traditional vaccine production methods:27 GSK ’ s virus-like-particle HPV vaccine , Cervarix also uses BEVS for production .
In 2015 , virologists in the Netherlands observed that expiration of the original patent on BEVS is facilitating “ commercial application of this expression system by @ @ @ @ @ @ @ is an enveloped double-stranded DNA virus that can infect many different types of insects .
The baculovirus Autographa californica multiple nucleopolyhedrovirus ( AcMNPV ) is the one most widely used by virologists and biotechnology companies to produce recombinant proteins .
News-Medical describes how “ mammalian cells are able to internalize baculovirus ” and how the Baculovirus Expression Vector System ( BEVS ) and can be used to express and deliver genes:29 When Protein Sciences first approached the FDA with evidence for fast tracking licensure of FluBlok , the National Vaccine Information Center ( @ @ @ @ @ @ @ a November 2009 meeting of the FDA Vaccines and Related Biological Products Advisory Committee ( VRBPAC ) questioning whether high protein content and using insect calls and insect viruses for vaccine production could compromise safety:30 FluBlok contains three times as much protein as other influenza vaccines .
There is always the potential for increased cross-reactive autoimmune responses in individuals who are genetically predisposed to autoimmunity and immune mediated neurological dysfunction .
I am thinking of the Bell ’ s Palsy case in these trials that may or may not have been triggered or @ @ @ @ @ @ @ small numbers of individuals in these clinical trials may not reveal the rarer but very serious complications involving demyelination of the brain and autoimmune disorders that have been reported following receipt of recombinant protein vaccines such as hepatitis B and HPV vaccines , including GBS , CNS vasculitis , rheumatoid arthritis , lupus and multiple sclerosis .
In the current effort to fast track the use of a new technology which clones hemagglutinin genes from three influenza viruses—which may be of human as well as mammal and bird origin—and splice them into baculoviruses @ @ @ @ @ @ @ caterpillar cells to produce the hemagglutinin contained in the new recombinant protein based influenza vaccine , there is always the possibility that adventitious agents contaminating insect cells could end up in the vaccines .
A 2005 World Health Organization document on regulation of candidate human vaccines states that “ Most insect cells may have viruses in them and infection can be hard to detect and difficult to eliminate…steps should be taken to eliminate them.
” The inadvertent contamination of polio vaccines with SV40 serves as a cautionary tale and the public will clearly @ @ @ @ @ @ @ screening is in place with this vaccine using an insect virus and insect cells for production , guaranteeing that no future unusual adverse effects will be seen as more people receive the vaccine .
In 2015 , a Protein Science official stated in Biotechnology Journal that the insect-based BEVS platform to produce vaccines must be carefully monitored for adventitious agent contamination:31 Sanofi and GSK with their combined manufacturing capacity are hoping to produce up to 600 million doses of their new coronavirus vaccine by 2021.32 Clinical trials are scheduled to begin in the @ @ @ @ @ @ @ trial results are positive , the companies plan to make the vaccine available to the public by the second half of 2021.4 Sanofi and GSK maintain they have an advantage in the race to be the first to put a licensed COVID-19 on the market , not only because they are using already-licensed technologies , but because of their ability to produce more doses of the vaccine quickly in the COVID-19 pandemic situation.33 GSK ’ s chief executive Emma Walmsley stated , “ The advantages are we both have scale in manufacturing .
@ @ @ @ @ @ @ their antigen [ the protein that forms the basis of Sanofi ’ s vaccine ] or our adjuvant.
” 34 Prior to this collaboration between GSK and Sanofi Pasteur , Sanofi was already in a COVID-19 vaccine partnership with Translate Bio , a clinical-stage messenger RNA ( mRNA ) therapeutics company in Massachusetts that is focusing on developing mRNA vaccines.35 GSK is also involved in providing its ASO3 squalene adjuvant for other companies and universities developing COVID-19 vaccines : Australia ’ s University of Queenland ; California ’ s Dynavax Technologies Corp ; @ @ @ @ @ @ @ s YangShengTang Group ; China ’ s Xiamen University , and China ’ s Clover Biopharmaceuticals Inc.36