April 19, 2020
To: (your legislator)
Re: COVID-19 vaccine testing
Many citizens and scientists are voicing their serious concerns over the way COVID-19 vaccine testing is being rushed. This letter outlines some of the most pressing issues with the development of a COVID-19 vaccine.
There is an unprecedented absence of completed animal studies, which are necessary to assess product efficacy and safety before being given to humans for the first time. Furthermore, there is no inert placebo control group in the very first human trial of the vaccine compound (NCT04283461). Not knowing the baseline rate of adverse medical events in a placebo group would make its safety profile indeterminable.
The COVID-19 virus is in a family of viruses for which vaccine development has proved dangerous, as animals receiving experimental SARS vaccines were not protected but instead predisposed to more severe disease when challenged with the wild virus [ref].
“The concern that is extrapolated from the FIPV vaccine experience to human SARS-CoV vaccines is whether vaccine recipients will develop more severe disease if they are exposed to or infected with SARS-CoV after neutralizing antibody titers decline. The second concern is whether recipients of a SARSCoV vaccine would be at risk of developing pulmonary immunopathology following infection with an unrelated human coronavirus e.g. 229E, OC43, HKU1 or NL63 that usually cause mild, self-limiting disease. Although findings from preclinical evaluation have revealed these concerns, studies in animal models may not be able to provide data to confirm or allay these concerns.”
“Animal models for SARS and MERS coronaviruses”:
Please take into consideration the safety risks and concerns of this rapid-pace of development, demand completed animal trials, require inert-placebo control groups before licensing, and proceed with caution. Public trust in vaccine products is at an all-time low. Failure to ensure that the trials on any COVID-19 vaccine product are conducted ethically and thoroughly will further erode trust.
Bernard D. Goldstein, Professor Emeritas with the University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pa. wrote:
“We in public health must recognize that the precautionary principle applies to our own actions, that when a public health action is proposed, the burden of proof—to ensure that all risks and consequences are taken into account—rests on us just as surely as it rests on others.”
The Precautionary Principle Also Applies to Public Health Actions
In attempts to produce a vaccine for another coronavirus, SARS, animal studies proved that the vaccine led to a worsening of the symptoms of SARS upon infection post-vaccination.
Evidence of inefficacy in the animal study portion of the testing prevented the progress of the vaccine to Phase I human studies. Covid-19 is a coronavirus, very similar to SARS in its mechanism and structure. It is unwise to accelerate testing of this vaccine and skip the animal safety studies that halted the previous vaccine in its development.
“In summary, we demonstrate that the immunization of BALB/c mice with the N protein of SARS-CoV causes severe pulmonary inflammation upon subsequent SARS-CoV infection, probably via the imbalance created between T cell activation and suppression, as well as by massive proinflammatory cytokine production.”
Dr Peter Hotez, Dean of the National School of Tropical Medicine at Baylor College of Medicine, told Reuters:
“I understand the importance of accelerating timelines for vaccines in general, but from everything I know, this is not the vaccine to be doing it with,” Hotez worked on the development of a vaccine for SARS (Severe Acute Respiratory Syndrome), the coronavirus behind a major 2003 outbreak, and found that some vaccinated animals developed more severe disease compared with unvaccinated animals when they were exposed to the virus. “There is a risk of immune enhancement,” said Hotez. “The way you reduce that risk is first you show it does not occur in laboratory animals.”
The following excerpts from peer reviewed studies voice similar concerns with the SARS-CoV vaccine (called DIV):
“These data raise significant concerns regarding DIV vaccine safety and highlight the need for additional studies of the molecular mechanisms governing DIV-induced eosinophilia and vaccine failure, especially in the more vulnerable aged-animal models of human disease.”
“However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.”
Pandemics of novel pathogens require immediate focus on prophylactic and treatment therapeutics to protect as many as possible from infection and to minimize loss of life. Recovery protocols, such as Vitamin C infusions and chloroquine, are saving lives worldwide and plasma convalescent therapy must begin as soon as available. Links to studies on known options can be found in Dr. Lyons-Weiler’s article cited below. There is growing concern that social-distancing alone is not enough. China utilized both distancing and therapeutics and has brought their cases under control in a remarkably short period of time. Without therapeutic interventions, the outbreak could go on for many months.
Excerpts from the SARS-CoV animal studies.
Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus. “Lung mononuclear infiltrates occurred in all groups after virus challenge but with increased infiltrates that contained eosinophils and increases in the eosinophil promoting IL-5 and IL-13 cytokines only in the vaccine groups. Inactivated MERS-CoV vaccine appears to carry a hypersensitive-type lung pathology risk from MERS-CoV infection that is similar to that found with inactivated SARS-CoV vaccines from SARS-CoV infection.” https://www.ncbi.nlm.nih.gov/pubmed/27269431
Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants.“VRP-N vaccines not only failed to protect from homologous or heterologous challenge, but resulted in enhanced immunopathology with eosinophilic infiltrates within the lungs of SARS-CoV-challenged mice. VRP-N-induced pathology presented at day 4, peaked around day 7, and persisted through day 14, and was likely mediated by cellular immune responses.” https://www.ncbi.nlm.nih.gov/pubmed/17194199
Immunization with Modified Vaccinia Virus Ankara-Based Recombinant Vaccine against Severe Acute Respiratory Syndrome Is Associated with Enhanced Hepatitis in Ferrets “Immunized ferrets developed a more rapid and vigorous neutralizing antibody response than control animals after challenge with SARS-CoV; however, they also exhibited strong inflammatory responses in liver tissue.”
1) Ahmed SS, Volkmuth W, Duca J. Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2. Sci Transl Med. 2015 Jul 1;7(294):294ra105. doi: 10.1126/scitranslmed.aab2354.
2) Agrawal AS, Tao X, Algaissi A. Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus. Hum Vaccin Immunother. 2016 Sep;12(9):2351-6. doi: 10.1080/21645515.2016.1177688. Epub 2016 Jun 7.
3) Boodman, E. 2020. Researchers rush to test coronavirus vaccine in people without knowing how well it works in animals STAT https://www.statnews.com/2020/03/11/researchers-rush-to-start-moderna-coronavirus-vaccine-trial-without-usual-animal-testing/
4)Deming D, Sheahan T, Heise M. 2006. Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants. PLoS Med. 2006 Dec;3(12):e525.
5) Gretebeck, Lisa M, and Kanta Subbarao. “Animal models for SARS and MERS coronaviruses.” Current opinion in virology vol. 13 (2015): 123-9. doi:10.1016/j.coviro.2015.06.009
6) Laguipo, Angela Betsaida B. “Could Rushing a Coronavirus Vaccine Cause More Harm?” News, 12 Mar. 2020, www.news-medical.net/news/20200312/Could-rushing-a-coronavirus-vaccine-cause-more-harm.aspx.
7) Lanese, N. 2020.Researchers fast-track coronavirus vaccine by skipping key animal testing first. LiveScience https://www.livescience.com/amp/coronavirus-vaccine-trial-no-animal-testing.html
8) Lyons-Weiler, et al. “How the COVID-19 Pandemic Will End.” Jameslyonsweiler.com, 16 Mar. 2020, jameslyonsweiler.com/2020/03/15/how-the-covid-19-pandemic-will-end/
9) Lyons-WeilerFollowEditor, James. “Moderna and US NIAID Poised to Endanger the World Population?” LinkedIn, www.linkedin.com/pulse/moderna-us-niaid-poised-endanger-world-population-james-lyons-weiler.
10) “Moderna Ships MRNA Vaccine Against Novel Coronavirus (MRNA-1273) for Phase 1 Study.” Moderna, Inc., investors.modernatx.com/news-releases/news-release-details/moderna-ships-mrna-vaccine-against-novel-coronavirus-mrna-1273.
11) “Safety and Immunogenicity Study of 2019-NCoV Vaccine (MRNA-1273) to Prevent SARS-CoV-2 Infection – Full Text View.” Full Text View – ClinicalTrials.gov, clinicaltrials.gov/ct2/show/NCT04283461
12) Tetro, JA 2020. Is COVID-19 receiving ADE from other coronaviruses? Microbes and Infection 22:72-73. https://www.sciencedirect.com/science/article/pii/S1286457920300344
13) Weingartl H, Czub M, Czub S, Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J Virol. 2004 Nov;78(22):12672-6.
14) Yong, Chean Yeah, et al. “Recent Advances in the Vaccine Development Against Middle East Respiratory Syndrome-Coronavirus.” Frontiers in Microbiology, Frontiers Media S.A., 2 Aug. 2019, www.ncbi.nlm.nih.gov/pmc/articles/PMC6688523/.
15) Vitamin C Study for Covid-19: http://orthomolecular.org/resources/omns/v16n18.shtml?fbclid=IwAR2LN4Vm07c29VwTNUrrbJscPf-5RcRDCsJbFFn3DscQlsIYeujJiddpfrc