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Covid-19: How long will it take to develop a vaccine?(This article was written in 2020)All vaccines induce both an antibody and a T-cell response. T-cells are white blood cells that attack cells infected with the virus, and antibodies (produced by B-cells) neutralise the virus so that it cannot infect cells to start with. Traditionally, the medical world has been focused on antibodies because they are easier to detect and "count", whereas it is not trivial to test your T-cells. T-cells are divided into CD4 cells ("helper" T cells) and CD8 cells ("cytotoxic" T cells). B-cells are stored in places called "germinal centers." A vaccine (or an infection) causes the immune system to "remember" the attacker and store both B-cells and T-cells so that they can easily be reactivated in case of a future attack. For the record, the fastest development of a vaccine ever was five years. For the record, forty years later we still don't have a vaccine against AIDS. In 2018, about 770,000 people died of AIDS worldwide. And nobody is talking about it anymore. We just learned to live with it, and we find cures that extend the lives of AIDS victims. We don't always find a vaccine. Even when we find it, it doesn't mean that the vaccine solves the problem: we do have a vaccine against measles, but measles still exists. John Wang, co-founder of the Chinese-American BioPharmaceutical Society, during a May 16 webinar, said that there are many signs that the virus will be with us for a long time and likely there will be a second wave in the winter, just like the flu, which mutates every year and requires annual vaccination. There are also signs that it damages the immune system. Also note that we could end up with a vaccine that prevents the disease but does not prevent transmission. For example, there are two polio vaccines. Developing countries use the inactivated polio vaccine IPV which is very effective at protecting individuals but does not prevent individuals from spreading it. European, North-american and east Asian countries use the oral vaccine OPV, which is a bit less effecting at protecting the individual but way more efficient in preventing the spreading. Thanks to the fact that Chinese scientists shared the genetic sequence in early January and posted it open source, more than 100 vaccines are already under development. But often the candidates are unsafe or ineffective, or both. The reason it takes years to develop a vaccine is that some vaccine candidates work well but only time can tell if they have dangerous side effects, and most of them are withdrawns because they turn out to be dangerous (you don't want the cure to cause more damage than the disease). Traditionally, the principle of a vaccine has been to use a live, weakened form of the virus to elicit the production of antibodies. That was the case of the first vaccine, invented in 1796 by Edward Jenner to prevent smallpox when he inoculated a boy with cowpox (the name "vaccine" comes from the Latin word for "cow", i.e, "vacca"). Examples of "live" attenuated vaccines are those for measles, mumps, chickenpox,smallpox, tuberculosis, and most flu vaccines. This kind of vaccines is very effective but of course it is dangerous because it involves the inoculation of a "live" virus. Inactivated vaccines (such as the ones for polio, rabies, hepatitis A and B) instead use a "dead" virus, typically cloning the protein that the virus uses to infiltrate our cells. Both Sinopharm and Sinovac in China are working on inactivated viruses. In particular, Sinovac has an inactivated vaccine candidate, based on their 2004 SARS vaccine. In general, Chinese companies are focusing on proven technologies. At least one of these vaccines has been administered to a selected group of people in China. The problem, ironically, is that China contained the virus and therefore doesn't have a situation of widespread contagion where the vaccine's effectiveness can be tested. Therefore it will have to test the vaccines in other countries, countries where thousands of people are being infected every day. The Max Planck Institute in Germany developed a vaccine candidate called VPM1002, which is based on the century-old Bacillus Calmette-Guerin (BCG) vaccine. Traditional inactivated and protein vaccines generate strong antibodies, but struggle to generate T-cell responses. Attenuated pathogen vaccines generate both, but risk causing the disease they are designed to prevent. A "recombinant" vaccine is made by extracting DNA from the virus and pasting it into the genome of a bacterium or yeast. If I understand correctly, this is basically a genetically modified virus that can't spread the infection but that does trigger the production of antibodies. The first recombinant protein vaccine was the hepatitis B vaccine, the first vaccine obtained via genetic engineering. In this case the DNA of a protein of hepatitis B virus is inserted in yeast. The protein is the one that triggers the desired response from the immune system and it's called the "antigen". Recombinant vaccines are "subunit vaccines", i.e. vaccines that only include the antigens that best stimulate the immune system. There are other kinds of subunit vaccines, notably the toxoid vaccines (diphtheria, tetanus, pertussis) that use toxins of the virus to stimulate the production of antibodies. Rather than delivering the DNA directly to cells, these vaccines use a harmless virus or bacterium as a vector, or carrier, to introduce the desired DNA into cells. Adenoviral vectors are being used to introduce the foreign DNA into the cells of the body. Adenoviral vectors are genetically-engineered viruses, designed to transport a gene of the deadly virus into our bodies to stimulate the immune system. Sarah Gilbert's team at Oxford is working on a recombinant DNA vaccine (called AZD1222) using her adenoviral vectored vaccine technology developed for the MERS vaccine. This vaccine used a chimpanzee-derived vector that they developed in 2012, dubbed ChAdOx1, based on an adenovirus discovered in chimpanzees, a weakened version of a common cold virus that causes infections in chimpanzees but that has been genetically modified to be harmless in humans. The Oxford team, through its spin-off company Vaccitech, has developed experimental vaccines not only for MERS but also for AIDS, malaria and tuberculosis. In June four countries (Italy, Germany, France and the Netherlands) already bought 400 million doses of the vaccine from AstraZeneca, who is supposed to commercialize it once the Oxford confirms that it works. CanSino Biologics in China, founded by former Sanofi vaccine developers, also developed a recombinant DNA vaccine using an adenoviral vectored vaccine technology, the one that they developed for their 2017 ebola vaccine. The "adenovirus" of CanSino`s vaccine is a weakened version of a common cold virus (Ad5). China (and only China) approved the vaccine, but only for emergency use, and so far it has never been used. No adenovirus vector vaccine has ever been approved by the FDA in the USA. Adenoviral vectors seem to be the current covid-19 vaccine front-runners. CanSino Biologics, Johnson & Johnson, and the University of Oxford are all using genetically engineered adenoviruses to make covid-19 vaccines. The technology is more than 30 years old, but it's yet to yield an effective vaccine for humans: the only commercial vaccine of this kind today is a rabies vaccine used to immunize wild animals. Originally, the adenovirus of choice was Ad5, the cause of the common cold. Ad5 is the "vector" originally used to deliver gene therapies, but in 1999 a teenage boy died after receiving an injection of an Ad5-based gene therapy. For two decades, adenoviral vectors have been tested to fight AIDS, malaria, and tuberculosis. Merck developed an Ad5-based vaccine for HIV, but that failed. CanSino and Oxford are still using Ad5, but now Johnson & Johnson is experimenting with a less common adenovirus, Ad26, in collaboration with Dan Barouch's team at Harvard Medical School. J&J has already developed several Ad26-based experimental vaccines for viruses like HIV, Zika and Ebola. The "Sputnik V" vaccine, developed by the Gamaleya Research Institute of Epidemiology and Microbiology in Moscow, is a mixed-vector vaccine, i.e. it uses two adenoviruses, specifically Ad26 for the first dose and Ad5 for the booster dose. Maryland-Based Novavax too has a recombinant vaccine, but based on ad-hoc nanoparticles instead of an adenovirus. They reused their experience developing the recombinant vaccine NanoFlu for the seasonal flu: they use a genetically-modified baculovirus, a virus that only infects insects, to grow proteins that, when injected in the human body via nanoparticles, trigger the human immune system to produce antibodies. There are now other genetic vaccines, besides adenoviral vector vaccines: mRNA vaccines and DNA vaccines. These three all have in common that they mimic a natural infection which stimulates our immune system to produce the T cells that can destroy cells infected with the real virus. Traditional vaccines, instead, stimulate B cells to make antibodies against the virus. T cells and B cells constitute our acquired immunity, developed by the body as it has confronted invading organisms such as viruses, bacteria and parasites. These so-called "adaptive" immune cells remember foreign invaders after their first encounter and are ready to fight them again in the future. A vaccine is basically a tool to generate these useful cells before the body is attacked. B-cells and T-cells are also called lymphocytes. B-cells fight bacteria and viruses by making proteins called antibodies. There are two main types of T-cells: helper T-cells and killer T-cells. Helper T-cells stimulate B-cells to make antibodies and help killer cells develop. Killer T-cells directly kill cells that have already been infected by a foreign invader. Once the virus infiltrates our cells, the antibodies from a traditional vaccine are useless. We need the T-cells to kill the invader, and adenovirus vector vaccines are the best method we found so far for inducing a T-cell response. Unlike traditional vaccines, which require the laborious production of actual viruses or viral proteins, gene-based vaccines are made from DNA or mRNA, and they can be designed on a computer in a matter of hours. Gene-based vaccines simply encode a chosen viral protein in DNA or mRNA. Let's start with mRNA vaccines, which have become very popular (read: Moderna in Boston, and German companies CureVac and BioNTech, Robin Shattock's team at Imperial College London, Fosum in Shanghai and Shanghai East Hospital of Tongji University) because in theory they are much faster to produce (they don't contain a live virus). Unfortunately, noone has ever made an RNA vaccine for humans. Rather than injecting subjects with a virus-like substance to stimulate antibody production by their immune system, mRNA vaccines give the body instructions to create those antibodies. The main problem to solve is the extreme instability of RNA. Because DNA is double-stranded, it is inherently more stable. Because RNA is so unstable, as of now, an mRNA vaccine would have to be stored at minus 80 degrees celsius until 30 minutes before being injected. The instability of RNA is an old topic of research. For example, Rhiju Das at Stanford has an entire lab that focuses on studying RNA's stability. In November 2020 BioNTech announced that its RNA vaccine offers 90% protection, Moderna claimed 94% protections for its own RNA vaccine, and Oxford claimed similar protection for its chimpanzee adenoviral vector vaccine ChAdOx1. San Diego's Inovio and Applied DNA of New York (in collaboration with Italy's Takis Biotech) are instead working on DNA vaccines. These vaccines insert DNA into the cells of the body with instructions to make the antigen proteins; a different procedure from the recombinant DNA vaccine that uses DNA from the coronavirus itself. Dan Barouch at Harvard developed a DNA vaccine that protects monkeys against covid-19 (paper). Inovio claims to have cut that design-to-dose time down to 18 months during the Ebola epidemic, to 9 months during the MERS epidemic, and 7 months during the Zika epidemic (from the moment the vaccine is designed to the moment it is administered to the first human in a clinical trial). Again, no DNA vaccine has ever been approved for humans: these were all experimental. The National Institute of Allergy and Infectious Diseases developed candidate DNA vaccines for in 2003, H5N1 flu in 2005, H1N1 flu in 2009, and Zika in 2016, but none has been approved. The same center developed an experimental mRNA vaccine against Zika that was tried on animals. It's important to remember that, in capitalist countries, pharmaceutical companies and biotech startups are issuing press releases for their shareholders and their investors, not for the purposes of public health. In mid-March Shibo Jiang, who discovered the virus, wrote an article in Nature magazine warning against deploying vaccines without adequate research. In August, China granted a patent for the covid-19 vaccine candidate Ad5-nCOV to CanSino. In August, Russia approved its "Sputnik V" vaccine, developed by the Gamaleya Research Institute of Epidemiology and Microbiology in Moscow, but after little human testing. 
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See also: Back to FAQ/ Q&A about Covid-19, Data on Covid-19 and selected sources, Covid-19: How it may change the World, The Clown & the Virus, The Clown & the Virus - Part 2, Trump's Virus, Sinophobia & Covid-19, Sinophobia & Covid-19 in US Media, Was covid-19 made in the USA? in China? Back to the world news |
| Email | Back to History | Back to the world news | Home | Support this website TM, ®, Copyright © 2020 Piero Scaruffi All rights reserved. |