This is the fourth in a series of articles that I’ve written for this journal about Covid-191-3. Last month, the Chinese started vaccinating military volunteers with a non-replicating, genetically modified adenovirus, type 5 (Ad5). It produces the SARS-CoV-2 spike glycoprotein (S) as an antigen3. However, some people will have pre-existing immunity to this common human virus. In addition, Dr. Ernesto Burgio wrote two very informative articles about this pandemic, as well as others in history4,5. He pointed out that viruses (including SARS-CoV-2) mutate and that the current pandemic was predicted – in vain5.
“The entire community of scientists in this field has been asking for years to prepare for the worst. Yet, as we will see, only the Asian countries -- which in the last two decades had faced the pre-pandemic alarms related to avian flu and SARS -- adequately prepared themselves to face the emergency, while the Western countries generally found themselves completely unprepared for the foretold pandemic. Conspiracy theorists and negationists have dominated the airwaves for a long time: even the painful American drama did not convince them to shut up.” 5
This month, the Russian government announced that it has started vaccinating its military with a vaccine developed by the Gamaleya Institute. It’s called Gam- Covid-Vac and Sputnik V. It uses two different types of genetically engineered, non-replicating adenovirus vectors, Ad5 and Ad26. They express the viral S protein. Hopefully, this will decrease the chances of pre-existing immunity reducing the vaccine’s effectiveness. So, unlike most vaccines in development, patients will receive a second booster shot. Frontline healthcare workers, doctors and teachers will begin receiving the first of two shots in October. Also, Johnson & Johnson’s vaccine candidate uses the Ad26 vector. AstraZeneca and the University of Oxford are developing a vaccine based on a chimpanzee adenovirus called ChAdOx13.
There are about 24 vaccine candidates that are in clinical trials and many more are in preclinical development6. China made a $1 billion loan to countries in Latin America and the Caribbean. China will make any coronavirus vaccine it develops available to these countries.
The following are in Phase 3 trials:
1. BBIBP-CorV, a genetically engineered, inactivated SARS-CoV-2 virus from the Wuhan Institute of Biological Products and the China National Pharmaceutical Group (Sinopharm).
2. CoronaVac, a different genetically engineered, inactivated SARS-CoV-2 virus from the Sinovac Research in China.
3. A self-amplifying mRNA that is encapsulated in a lipid nanoparticle (LNP) by Moderna (described briefly in my previous article) 3.
4. Ad5-CoV that uses the Ad5 vector, from CanSino Biologics.
The following are in Phase 2/3 trials:
1. A Bacillus Calmette-Guerin (BCG) live, attenuated bovine tuberculosis bacillus, Mycobacterium bovis, from the University of Melbourne and Murdoch Children’s Research Center, Radboud University Medical Center (in Utrecht) and the Faustman Lab at Massachusetts General Hospital. It has been used since 1922 as a tuberculosis vaccine (described briefly in my previous article). It’s also been the standard therapy for bladder cancer since 19773.
2. AZD1222, a chimpanzee adenovirus, ChAdOx1, from the University of Oxford, AstraZeneca, the Jenner Institute (described briefly in my previous article) 3. 3. Another self-amplifying mRNA that is encapsulated in an LNP by Pfizer and BioNTech (described briefly in my previous article) 3.
The following are in Phase 2 trials:
1. An adjuvant recombinant protein (receptor binding domain, RBD, of the S protein) from Anhui Zhifei Longcom Biopharmaceutical and the Institute of Microbiology of the Chinese Academy of Sciences.
2. ZyCoV-D, a genetically engineered plasmid (a small piece of DNA that encodes a viral antigen) from Zydus Cadila, developed at the Vaccine Technology Centre in Ahmedabad, India.
3. Covaxin, which uses an inactivated form of the SARS-CoV-2 virus. It’s from the Bharat Biotech and National Institute of Virology in India.
The following are in Phase 1/2 trials:
1. BBIBP-CorV, which is an inactivated SARS-CoV-2 virus, from the Beijing Institute of Biological Products and Sinopharm.
2. GX-19, which uses a piece of DNA that encodes a viral antigen, from Genexine in Korea.
3. A self-amplifying mRNA that encodes a viral antigen from the Imperial College London.
3. LUNAR-COV19, a DNA vaccine from Arcturus Therapeutics and Duke-NUS Medical School.
4. INO-4800, a DNA vaccine from Inovio Pharmaceuticals. It’s being tested in the Center for Pharmaceutical Research in Kansas City and the University of Pennsylvania in Philadelphia.
Six more vaccine candidates are in Phase 1 trials. Many more are in preclinical development6. One of the more promising ones was described in one of my previous articles1. It was developed by Sanofi, in France. It uses a conventional approach. Its Covid-19 vaccine produces SARS-CoV-2 spike proteins in genetically engineered insect cells. This is the same process it uses for its commercial influenza vaccine, FluBlok. Sanofi and GlaxoSmithKline (GSK) were given funds to supply United States government with 100 million doses of Covid-19 vaccine. The vaccine candidate will use GSK’s established pandemic adjuvant technology, called AS03. It contains molecules that excite the immune system and boost vaccine potency. Clinical trials will start later this year, and the firms hope to have a vaccine available in the second half of 2021. It’s the first time these two companies have joined to develop a Covid-19 vaccine.
However, one can only make an educated guess about how long immunity might last in people who have been infected with SARS-CoV-2 and were either asymptomatic or recovered from the Covid-19 disease. Fortunately, the immune systems of patients who recovered from Covid-19 had a robust immune response7. Their immune systems were able to recognize SARS-CoV-2 in many ways. Their memory T-cells were able to target several viral antigens, especially the S protein. This should make it easier to develop new vaccines.
In addition, some people have a natural, pre-existing immunity to infection due to antibodies and memory cells formed after previous exposure to other coronaviruses that can cause the common cold. A recent study showed that there are memory T cells in people who had never been exposed to the SARS-CoV-2 virus8. This pre-existing immunity affects the models used to predict the future course of this pandemic9. When a hypothetical 30% immunity was added to one epidemiological model, the virus faded away in the near future before returning in three or four years9.
CRISPR, a new technology that could produce better tests for active infections
One of the keys to controlling the Covid-19 pandemic is developing a rapid, reliable test for active infections by the SARS-CoV-2 virus. Often, the popular media calls this a test for Covid-19. Actually, many people become infected with the virus, but never develop the disease.
One of the most important new technologies called CRISPR may be capable of providing such a test. One of my previous articles described the use of CRISPR to produce potentially safe and effective treatments (and possibly a cure) for Covid-193. Another described how gene editing using CRISPR technology might become produce new foods inexpensively to feed a growing population10. One such test was developed by Sherlock Biosciences. They have formed a partnership with Binx Health Limited to mass-produce diagnostic tests that provide results within 20 minutes and can be performed not just in a hospital, but also a physician’s office, a supermarket, and many workplaces. Binx Health already provides convenient tests for sexually transmitted diseases that can be done at home. The CRISPR-based test uses a single-use cartridge system and the SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) platform. It will use Binx’s electrochemical detection system to analyze nasal swab samples and report a “detected” or “not detected” result. The SHERLOCK method programs a CRISPR molecule to detect the presence of a specific SARS-CoV-2 genetic signature in specimens collected from patients11. Chinese scientists have reported a similar CRISPR-based test10.
We need to learn more. The global effort
A safe and effective vaccine and accurate tests for viral infections could save countless millions of lives. Still, they will not be sufficient to provide herd immunity in the USA and most other countries. As long as people have the freedom to avoid vaccination and even to deny science, herd immunity can’t be achieved. In addition, the SARS-CoV-2 and other viruses mutate continuously.
Scientists continue to work together, while disregarding the hateful nonsense that comes from some politicians and their supporters. As described in a previous article, this is NOT a China virus. It’s possible that SARS-CoV-2 began circulating as early as December 2019 in California and New York12. It went unnoticed because we had no experience with the first SARS-CoV, which caused a relatively brief epidemic in China and other Asian countries. As a result, they were able to detect it first. Blaming the Chinese is like blaming the messenger. Scientists know that it’s almost impossible to prove where this epidemic started. Moreover, we should follow the principles of Total Quality Management (TQM). Serious, complex problems (like Covid-19) have many causes (such as human encroachment into previously remote ecosystems and Global Climate Change). It’s far more important to find out who will fix the problem than who might have caused it. Fear, hatred and anger do not help.
The international scientific community is sequencing the genomes of SARS-CoV-2 that are isolated from patients. As described previously in this journal, a mutation that changed a guanine (G) to adenine (A) at position 23,403 in the Wuhan reference strain was found months ago1. This changed an aspartic acid residue to a glycine at position 614 in the S protein. This mutated strain (D614G) has become dominant across the world and is more infective than the original strain13. Scientists from around the world continue submitting their data to an open access database, GISAID (The Global Initiative for Sharing All Influenza Data), with headquarters in Munich, Germany1,13. It is the primary Covid-19 sequence database resource for genomic data. Their “intent is to complement what they provide with visualizations and summary data specifically intended to support the immunology and vaccine communities, and to alert the broader community to changes in frequency of mutations that might signal positive selection and a change in either viral phenotype or antigenicity” 14. It has also been the primary sequence database for influenza. As of 19 August, about 83,000 genomic sequences of the SARS-CoV-2 virus (also known as hCoV-19) have been deposited and shared in the GISAID database. In addition, a new form of the swine flu (influenza) has entered the watch list for the next possible pandemic13. It is a reassortment virus. That is, its genome has parts from two or more different viruses. As stated on their website, it’s very important to look for new viruses that can cross from animals into humans (called zoonotic viruses).
The search for previously unknown zoonotic viruses was being done in recent years by virus hunters. When searching in the caves of Yunnan, China, they found several coronaviruses in bats that are very similar to that of SARS-CoV-215. As described by Dr. Ernesto Burgio in this journal5, plans were made to genetically modify some of these viruses to study their infectious and pathogenic potential. However, harsh criticisms and requests for a moratorium against this line of research followed16. This could be problematic because such a moratorium could be applied only to research conducted in the main laboratories (with safety and international controls), but not to any genetic manipulation done in far less safe and uncontrolled laboratories5. However, it should be emphasized that the SARS-CoV-2 virus was NOT made by purposeful manipulation in a lab1,17.
Another key point in the recent article by Dr. Ernesto Burgio is that new serotypes of viruses emerge5. Some can be much deadlier than the original virus and others can be deadlier in people who received a vaccine that was safe and effective against the original serotype5. This was the case with a vaccine for Dengue fever1,18. So, it’s important for the international community of scientists to increase their efforts to find new viruses. There have been calls to fund a BIOSCAN, the Earth BioGenome Project (EBP), and the Global Virome Project (GVP )19,21.
A Pilot Project, called PREDICT, was initiated in the USA when George W. Bush and Barack Obama were Presidents22. It was studying and identifying animal viruses that might infect humans, so new pandemics could be predicted. Investigators collected over 140,000 biological samples from animals and found over 1000 new viruses, including a new strain of Ebola. The Federal government stopped funding this program rather quietly, while the nation was distracted with an attempt to impeach President Trump. This was 25 October, 2019. In just two months, SARS-CoV-2 and Covid-19 emerged.
As described recently, a synergistic, holistic, ecological and evolutionary process perspective is needed to understand how viruses spillover into human populations23. Viruses are not static. They are dynamic and ever-changing. We must identify potential pathogenic viruses, track them and monitor their genomes. There are a Global Influenza Surveillance and Response System that monitors the quickly evolving and recombining influenza virus in a timely manner. It has served for over half a century as a way to issue warnings when influenza viruses with pandemic potential. In the recent past, China and the USA have led response activities for several epidemics and pandemics. They used a One Health perspective. It is based on systems thinking. Multidisciplinary teams study interacting processes that occur at both macro- and micro-scales, including pathogen, host and environment23.
China–US partnerships have focused on improving early-warning capabilities23. This includes the US CDC Global Disease Detection program (CDC-GDDP), the US Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) Program, the WHO, OIE and FAO’s collaborative global early-warning system for animal diseases transmissible to humans (GLEWS), and the China National Global Virome Initiative (CNGVI, part of the Global Virome Project, the PREDICT program, and joint research supported by the US National Institutes of Health (NIH) to define the origin of SARS- and MERS-like coronaviruses and identify other SARS coronavirus mammalian infections in China)23.
International collaborations exist between healthcare workers and people working for governments, research institutes, corporations and universities. We continue our efforts to learn more about virology in general and the SARS-CoV-2 virus in particular. One of our biggest challenges is communication. Many eligible voters in the USA deny science and think this pandemic is either a hoax, or something that can’t hurt them. This endangers them, their families and their neighbors. But the danger goes far beyond this pandemic. Denial of the science of Global Climate Change and rise in sea levels threatens our children, grandchildren and great-grandchildren. This denial of science and humanity is echoed by modern-day slave masters who run the prison-industrial complex. The white male privilege that I and other men like me enjoy is a huge part of the problem. All too many men use this privilege to treat women and the environment as commodities to be consumed then disposed of when done. We must give up our privilege and gain some humanity. We must recognize the pain and pure Evil that racist, misogynistic and xenophobic attitudes cause. Education is a powerful tool to do this. That is one reason why I wrote an article that debunked the myth of gender differences in intelligence24 and have been writing these articles about Covid-19 and science.
In my opinion, there has been a struggle between slavery and abolition in the USA for centuries. Too many people believe that slavery in the USA was abolished on 16 December, 1865 when the 13th Amendment to the Constitution was ratified. It was not. There is an escape clause: “except as a punishment for crime whereof the party shall have been duly convicted”. So, African-Americans could be arrested and convicted of failing to pay rent when they were sharecroppers, looking at or touching a white woman, observing a white man commit a crime and then testifying in court, trying to vote, for being a former judge who had sentenced a white man for a crime, or for just being black. Today, African-Americans are being arrested for protesting peacefully, running from the police, driving while being black or just being “uppity” or “resisting arrest”. This has expanded into a prison-industrial complex in which prisoners work under inhumane conditions, subject to punishment without cause. They earn no money while the corporate stock holders and upper executives get richer – just like the Plantation owners in the Old South.
So, next month I will propose that there have been five wars for slavery in the USA: the Revolutionary War, the War of 1812, the Mexican-American War, the Civil War and the current war system that started with the end of Reconstruction.
There will be a crucial battle in this cold war on 3 November of this year when national elections happen. In my opinion, the course of the Covid-19 pandemic and the lives of millions of American citizens will depend on the outcome of the election. We must emphasize the importance of science and the lives of our children as we try to communicate our message better.
1 Smith, R.E. Developing vaccines and treatments for Covid-19. Humans are not the enemy. Wall Street International, 24 May, 2020.
2Smith, R.E. Developing vaccines and treatments for Covid-19. Progress report. Wall Street International, 24 June, 2020.
3 Smith, R.E. China starts to vaccinate its military personnel. Developing vaccines and treatments for Covid-19. Progress report. Wall Street International, July 24, 2020.
4 Burgio E., 2020, Covid-19: the Italian Drama – Four avoidable risk factors, Wall Street International, 21 April, 2020.
5 Burgio, E. A pandemic foretold (in vain). A last report. Wall Street International, 4 August, 2020.
6 Craven, J. Covid-19 vaccine tracker. Regulatory Focus, 13 August, 2020.
7 Grifoni, A. et al. Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with Covid-19 Disease and Unexposed Individuals. Cell, 2020.
8 Mateus, J. et al. Selective and cross-reactive SARS-CoV-2 epitopes in unexposed people. Science, published in advance online, 4 August, 2020.
9 Kissler, S.M. et al. Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period, Science, Volume 368, pp. 860-868, 22 May, 2020.
10 Smith, R.E. Using CRISPR Gene Editing to Create New Foods. An Important Part of the Fourth Industrial Revolution. Wall Street International, 24 May, 2019.
11 Eckert, A. First point-of care test for Covid-19 leveraging CRISPR technology. Genetic Engineering & Biotechnology News, 1 July, 2020.
12 Davis, J.T. et al. Estimating the establishment of local transmission and the cryptic phase of the Covid-19 pandemic in the USA Preprint at medRxiv, 2020.
13 GISAID – Initiative. Accessed 19 August, 2020.
14 Korber, B., Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2. bioRx preprint, 30 April, 2020.
15 Qiu J., How China’s ‘Bat Woman’ Hunted Down Viruses from SARS to the New Coronavirus, Scientific American, Volume 322, pp. 24-32, June 2020.
16 Butler, D. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nature Medicine, Volume 21, pp. 1508–1513, 2015.
17 Andersen, K.G. et al. Proximal Origin of SARS-CoV-2. Nature Medicine, Volume 26, pages 450-455, 2020.
18 Peeples, L. Avoiding Pitfalls in the Pursuit of a Covid-19 Vaccine. Proceedings of the National Academy of Sciences, Volume 117, pages 8218-8221, 2020. 19 Kress, W.J. et al. Intercepting pandemics through genomics. Proceedings of the National Academy of Sciences, published online, 23 June, 2020.
20 Carroll, D. et al. The Global Virome Project. Science, Volume 359, pp. 872-874, 2020.
21 Carlson, C.J. From PREDICT to prevent, one pandemic later. The Lancet, published online 31 March, 2020.
22 McNeil Jr, D. Scientists were hunting for the next Ebola. Now the U.S. has cut off their funding. New York Times, 25 Oct 2019.
23 23 Evans, T.S. et al. Synergistic China-US ecological research is essential for global emerging infectious disease preparedness. EcoHealth, Volume 17, pp. 160-173, 2020.