CORONAVIRUS AND ALL PANDEMICS SOLUTION IS COMING SOON.
We are investing to eradicate CORONA VIRUS and all potential PANDEMICS from the face of the planet.
The Doers Need Not Wait For The Going To Get Tough For Them To Get Going.
We are working with Global Impact Investors and Funds to align money to solve world problems. Today we are working with the researchers using advanced physics — biology — chemistry and nanotechnology converged thought process to find an expedited vaccine for corona virus and make a sustainable system to bring vaccines to market within days and avoid loss of human life. If you would like to contribute through wisdom or money, please extend hand to serve humanity.
What’s the urgency of us aligning this capital to the doers?
Vaccines are really our most successful tool to prevent an infectious disease. It used to take a long time to make vaccines, because scientists had to isolate and grow the virus in the lab. But now, it’s possible to skip that step altogether and build a vaccine based on a virus’ genetic sequence. Chinese scientists made that genetic sequence from the new coronavirus public in early January, just weeks after the first infections with the virus were reported. That prompted several labs including those we support to start work on building a vaccine. Vaccines work by teaching an individual’s immune system to recognize an invading virus and neutralize it. This vaccine is called DNA vaccine. They’ll first turn pieces of the new coronavirus’ genetic code (which is RNA) into complementary snippets of DNA. These snippets will then be injected into someone’s skin, where they will be taken up by skin cells. The skin cells will then turn those DNA sequences into proteins identical to the ones a virus would produce, and those will be what “teaches” the immune system to recognize the new virus. Our researchers are in the process of determining which viral sequences produce the best “teachers.” This isn’t researchers first stab at rapid vaccine development. We have been working on a vaccine for Ebola after an outbreak of that virus in 2014. Including the initial time needed for animal testing and human safety testing, researchers are able to go from no vaccine to a vaccine tested in the clinic in about 18 months — 15 to 18 months. They also made a vaccine against the coronavirus that causes Middle East respiratory syndrome, after an outbreak in South Korea. And we were able to design and develop and move into the clinic in 11 months. But with DNA vaccines, this time shall reduce to weeks and days. That’s our effort to save lives when they need help.
No one can really be sure what will work, but you tend to want to focus on things that are important for [cellular] entry. With the experience or SARS and MERS we are working to bring to the world the following long term solutions
1. DNA Vaccine Based solution : The work involving designing the vaccine constructs — for eg, producing the right target antigens, viral proteins that are targeted by the immune system, followed by testing in animal models to show that they are protective and safe.
2. Global coordination through WHO / CDC : This is needed for various efforts towards cure in vaccine technologies, such as nucleic acid vaccines, which are DNA- and RNA-based vaccines that produce vaccine antigen in our own body. This reduces the vaccine development times to few days from almost five to ten years.
3. Lack Of Virus Samples : Currently, we lack virus isolates or samples of virus to test vaccines against. We also lack antibodies to make sure vaccine is in good shape. We need virus in order to test if immune response induced by vaccine works. Also, we need to establish what animals to test on. We are helping this all placing capital and talent in organizations that are far advanced in this field.
4. Improvement In Surveillance : To try to prevent large outbreaks/pandemics, we need to improve surveillance in both humans/animals worldwide as well as invest in risk assessment, allowing scientists to evaluate the potential threat to human health from virus, for detected viruses. We are developing a proactive solution in this space.
5. Novel Vaccine Approaches : Global action is needed to invest in novel vaccine approaches that can be employed quickly whenever a new virus like coronavirus, Zika, Ebola, influenza emerge. Currently, responses to emerging pathogens are mostly reactive. We are helping build proactive approaches. As soon as the COVID-19 genetic sequences became available in January, our researchers started designing DNA cassettes that encode proteins of SARS-CoV-2, the virus that causes COVID-19. Their basic approach to vaccine design is to change the nucleotide sequences of these genes to modify the predicted mRNA structures for optimal expression once inside people so that these transcripts abundantly produce the antigens people’s immune systems will recognize. The DNA is injected intramuscularly, then brief electric pulses applied to the site via small needles make the cell membranes more permeable to the genetic material. Then the human cells make viral mRNA and protein from the construct, thereby priming the immune system to fight the virus.
None of that even comes close to what might be needed to protect the world’s population in the worst-case scenario. But if the new coronavirus is seasonal in nature, as many respiratory viruses are, time might be on our vaccine makers side. Influenza, for instance, in most of the world typically transmits in winter and disappears in summer. If [2019-nCoV] behaves anything like flu, there will be seasonal transmission and then it will go down and there will be a recrudescence in the fall. So it could be even 1 year down the road before we see a large wave of disease. And it could be that a vaccine then plays a role in a timely fashion. Widespread infection in populations — which may be happening in Wuhan, China, now — can also lead to lasting immunity in many people, reducing the need for a vaccine.
For knowing more about viruses and DNA vaccines, please read below
Coronavirus Vaccine :
The current threat of avian influenza to the human population, the potential for the reemergence of severe acute respiratory syndrome (SARS)-associated coronavirus, and the identification of multiple novel respiratory viruses underline the necessity for the development of therapeutic and preventive strategies to combat viral infection. Vaccine development is a key component in the prevention of widespread viral infection and in the reduction of morbidity and mortality associated with many viral infections. In this part, coronavirus vaccine, especially SARS-CoV vaccines are mainly discussed.
Coronavirus vaccines can be inactivated coronavirus, live attenuated coronavirus, or S protein-based. Besides, there are still vectored vaccines, DNA vaccines, and combination vaccines against coronaviruses. Vaccines targeting several animal CoVs have been developed, and some have been demonstrated to be efficacious in preventing viral infection. However, a phenomenon of enhanced disease following vaccination has been observed in cats upon infection with feline infectious peritonitis virus following previous infection, vaccination, or passive transfer of antibody. The phenomenon is not fully understood but is believed to be a result of enhanced uptake and spread of the virus through binding of virus-antibody immune complexes to Fc receptors on the surfaces of macrophages; low-titer (subneutralizing) antibodies directed against the S protein are mainly responsible. Although antibody enhancement appears to be limited to feline infectious peritonitis virus among CoVs, similar concerns have been raised with regard to SARS-CoV. Previously infected mice and hamsters are protected from subsequent infection with SARS-CoV in the absence of enhanced disease, and vaccine studies and passive immunoprophylaxis performed with mice and hamsters suggest that previous exposure and the presence of NAbs provide protection.
Inactivated Coronavirus Vaccine :
The immunogenicity and efficacy of inactivated SARS-CoV vaccines have been established in experimental animals, and one such vaccine is being evaluated in a clinical trial. However, the development of inactivated vaccines requires the propagation of high titers of infectious virus, which in the case of SARS-CoV requires biosafety level 3-enhanced precautions and is a safety concern for production. Additionally, incomplete inactivation of the vaccine virus presents a potential public health threat. Production workers are at risk for infection during handling of concentrated live SARS-CoV, incomplete virus inactivation may cause SARS outbreaks among the vaccinated populations, and some viral proteins may induce harmful immune or inflammatory responses, even causing SARS-like diseases
Towards a pandemic ?
It’s very, very transmissible, and it almost certainly is going to be a pandemic.
This brings us to the scientists and experts who are doing just that, throwing everything they have at this public health issue. Some are focused on treating patients with existing or novel therapeutics, others are focused on stopping transmission between individuals by developing a vaccine. Luckily for scientists, lessons learned during the 2013–16 West African Ebola epidemic are now enabling the fast-track development of vaccines, without compromising their safety and efficacy.
Of course, it is critical to learn more about this specific novel virus, including its source and why transmission appears to be more efficient than with other coronaviruses.
Developing Therapeutics and Vaccines for Coronaviruses — Novel vaccines for a novel coronavirus :
CEPI, the Coalition for Epidemic Preparedness Innovations : One sign of the breakneck pace was the announcement on 23 January by the Coalition for Epidemic Preparedness Innovations (CEPI) that it will give three companies a total of $12.5 million to develop 2019-CoV vaccines. A nonprofit formed in 2016 solely to fund and shepherd the development of new vaccines against emerging infectious diseases, CEPI is trying to have vaccines developed and tested faster than any previous effort, anywhere, ever. Each of the three efforts that CEPI supports began within hours after Chinese researchers first posted a sequence of 2019-CoV in a public database. CEPI was created when people realized that an Ebola vaccine had been under development for a decade and it still took more than a year to get it to people when the 2014 Ebola outbreak occurred in western Africa.
- Inovio Pharmaceuticals Inc. and its “DNA platform : Funded by CEPI, Inovio, another company working on a 2019-nCoV vaccine with help from CEPI, began its project that same Saturday morning. Inovio produces vaccines made of DNA. It also has a MERS vaccine — which is further along than Moderna’s, already having entered human trials — that also relies on the spike protein. The team worked around the clock and was able to design a spike-focused vaccine by that Sunday night. Both Moderna and Inovio say they could have enough vaccine produced 1 month from now to begin animal testing.
When COVID-19 came on the scene, Vaccine & Immunotherapy Center at the Wistar Institute in Philadelphia were already part of a project led by pharmaceutical company Inovio to develop a DNA-based vaccine for Middle East Respiratory Syndrome (MERS), which is caused by a coronavirus. The Coalition for Epidemic Preparedness Innovation (CEPI), whose mission is to accelerate development of vaccines in epidemic situations, funds that project and reached out to Inovio and Weiner to discuss extending the collaboration to vaccine development efforts for the new coronavirus. They agreed and CEPI announced the expanded funding — up to $56 million — on January 23.
They had been paying very close attention to the [COVID-19] cases increasing over Christmas in China. As soon as the COVID-19 genetic sequences became available in January, Weiner’s team, and collaborators from Inovio, Université Laval, the National Institutes of Health’s Rocky Mountain Laboratories, and elsewhere, started designing DNA cassettes that encode proteins of SARS-CoV-2, the virus that causes COVID-19. Their basic approach to vaccine design was to change the nucleotide sequences of these genes to modify the predicted mRNA structures for optimal expression once inside people so that these transcripts abundantly produce the antigens people’s immune systems will recognize. The DNA is injected intramuscularly, then brief electric pulses applied to the site via small needles make the cell membranes more permeable to the genetic material. Then the human cells make viral mRNA and protein from the construct, thereby priming the immune system to fight the virus. When the group at Wistar and their collaborators went through a similar process for MERS, they chose about 14 different viral proteins and put their corresponding genes together in different combinations that they tested for effectiveness in different cell types. In that case, they went through all the steps, from synthetic DNA to a Phase 1 clinical trial, in about 11 months. The results, published in 2019, showed immune responses to the vaccine, such as the production of neutralizing antibodies and the activation of cytotoxic T lymphocytes, also known as killer T cells. There were no serious adverse events, and a Phase 2 trial is in the works. In terms of choosing which viral proteins will produce the best immune response, no one can really be sure what will work, but you tend to want to focus on things that are important for entry. For instance, the spike proteins that are common to coronaviruses are a good place to start. Having the genome sequence allows you to design vaccines for this that are likely to work [based on] what we know about other coronaviruses. The genome sequencing is absolutely crucial. In the same January 23 announcement, CEPI formalized funding for two other COVID-19 vaccine development projects: an unspecified amount to a collaboration between the National Institute of Allergy and Infectious Diseases (NIAID) and Moderna, a biotech company based in Cambridge, MA, for the development of an mRNA-based vaccine, and up to $10.6 million to the University of Queensland. The Australian team is working on a vaccine composed of synthetic viral proteins with an added stabilization domain called a molecular clamp. The idea is that by holding the synthetic proteins in the conformation that so-called viral fusion proteins maintain before they merge with a host cell, the molecular clamp allows for better recognition of these proteins by the host immune system, leading to greater vaccine efficacy. On February 18, the Biomedical Advanced Research and Development Authority (BARDA), part of the United States Department of Health and Human Services, and pharmaceutical company Sanofi Pasteur publicized a collaboration to develop their own version of a recombinant protein–based vaccine. Sanofi is already the maker of Flublok, an influenza vaccine built on this approach that is licensed in the US. BARDA will also collaborate with pharmaceutical company Janssen on a project to develop a COVID-19 vaccine.
2. University Of Queensland : CEPI’s third grant is going to researchers at the University of Queensland. They are developing a vaccine consisting of viral proteins produced in cell cultures, an older technology. Their aspirational goal is to have a candidate vaccine ready for human tests 16 weeks from now. This is incredibly ambitious and they can provide no guarantee that we can meet this target. But their team is working as hard and fast as they possibly can. It is reassuring to them that they are not the only team tasked with a response.
University of Queensland and its “protein clamp platform. CEPI and researchers from the University of Queensland in Brisbane, Australia, have found a way to clamp down on the coronavirus to keep it from infecting cells. The Queensland group had already been working with CEPI on molecular clamp vaccines against other viruses for about a year. A molecular clamp is a protein stitched onto another protein, in this case the coronavirus’ spike protein. With SARS and MERS, spike proteins work a bit like malleable lock picks, changing shape to interact with a protein on the surface of human cells and gain entry into them. The 3-D structure of SARS-CoV-2’s spike protein is also a shape-shifter. But the new coronavirus’ spike protein clings 10 to 20 times as tightly to its target on human cells as the SARS version does. Holding on tighter may help the new virus spread more easily from person to person. Scientists have determined the 3-D structure of the COVID-19 coronavirus’ spike protein which helps the virus enter cells. The work reveals that the protein binds more tightly to proteins on the surface of human cells than the SARS’ version of the protein does. Tighter binding may account for the new virus’s greater infectivity. The molecular clamp the Queensland team devised keeps the spike protein from shape-shifting, locking it in a form that triggers antibody production and thus making it a potent vaccine. The team uses mammalian cells to produce the vaccine, and a specialized machine determines which cells are churning out clamped protein. University of Queensland in Brisbane, Australia, thinks they can do even better. They , too, has a vaccine that’s based on the virus’ genetic sequence. The Queensland team has come up with an approach it calls the molecular clamp. It works by improving the body’s immune response to certain viral proteins. Their goal is to be able to hit 16 weeks from sequence information to having a product that is shown to be safe and effective and is ready for administration to the first humans. They are right now, also trying to figure out which genetic sequences will be most effective at helping the immune system recognize the coronavirus. Next steps will be moving into animal models for testing and also working out how to scale up to get to the levels that would be required in humans and beyond. With the machine, researchers can “do things that would have taken weeks before in just days. Laboratory testing may start within weeks. Safety testing in people may begin in months, but it will take much longer for the vaccine to be ready for general use. When the Queensland group began working with CEPI to develop a molecular clamp vaccine, they thought it would take three years as a test case. But the emergence of the new coronavirus forced the researchers to accelerate their efforts. Still, estimates say it will be at least a year before the vaccine will be ready. Both team in Australia and in Philadelphia, in collaboration with the pharmaceutical company Inovio, are getting financial support from a fairly new organization called CEPI, the Coalition for Epidemic Preparedness Innovations. CEPI is a global partnership of public, private and philanthropic organizations; it’s also supporting efforts at the biotech companies Moderna and CureVac.
3. Moderna : After the release of the Chinese genetic sequence, it all That on Friday evening, 10 January, in Bethesda, Maryland, home of the U.S. National Institute of Allergy and Infectious Diseases (NIAID). NIAID’s Vaccine Research Center, began to analyze the sequence on Saturday morning. The following Monday, they discussed their findings with researchers at Moderna, a vaccinemaker. On Tuesday, they signed a deal to collaborate. Moderna makes vaccines by converting viral sequences into messenger RNA (mRNA). When injected into the body, the mRNA causes the body to produce a viral protein that can trigger the desired immune response.
Moderna already has nine vaccines in clinical trials that use the mRNA platform. It was a really, really hard scientific challenge to make the first one, but once they got the first one working, the next one became really easy: They got the coronavirus sequence, and this is just another one. It’s the same manufacturing process by the same group in the same room. NIAID-funded scientists are exploring ways to treat and prevent human coronavirus infections by working to develop new antibodies, drugs, and vaccines that block entry to cells, delay the immune system response, or block viral replication. For COVID-19, NIAID scientists, working in Bethesda, Md., and Hamilton, Mont., are preparing to test the antiviral drug remdesivir, which has shown promise against other coronaviruses in animal models. NIAID is exploring other broad-spectrum antiviral compounds for activity against COVID-19. NIAID also plans to evaluate Kaletra, also known as lopinavir and ritonavir, and interferon-beta for their activity against COVID-19. The NIAID Vaccine Research Center (VRC) is drawing on broad research experience with coronaviruses, combined with a wide network of collaborators from academia, other government agencies and industry, on the development of a vaccine candidate expressing the viral spike protein of SARS-CoV-2 using a messenger RNA vaccine platform technology. NIAID anticipates the experimental vaccine will be ready for clinical testing in the coming months. NIAID scientists at Rocky Mountain Laboratories are collaborating with Oxford University investigators on the development of a chimpanzee adenovirus-vectored vaccine candidate against COVID-19. In addition, NIAID-supported scientists also are working to see if vaccines developed for SARS are effective against COVID-19. Grantees studying MERS are working to develop vaccines that target the viral Spike protein of a live, attenuated MERS vaccine, which is a type of vaccine that contains a version of the living microbe that has been weakened in the lab so it cannot cause disease. Grantees and NIAID VRC investigators are using knowledge learned from SARS vaccine development to create MERS treatments. One method for MERS uses neutralizing monoclonal antibodies — developed from a recovered MERS patient and immunized rhesus macaques — that target multiple sites on the virus S protein. NIAID has also supported the clinical testing of two promising antibody-based therapeutics, which prevent the virus from infecting and entering cells. NIAID conducted a phase 1 clinical trial of SAB-301, an experimental MERS treatment developed from cattle that make human antibodies. This was shown to be safe and well tolerated in healthy adults. More recently, NIAID supported a Phase I clinical trial of a combination of two monoclonal antibodies, REGN3048 and REGN 3051, and demonstrated this combination was also safe and well tolerated. Planning for follow on Phase 2/3 efficacy studies using SAB-301 is currently ongoing with partners where MERS is endemic, including the Kingdom of Saudi Arabia. One of the nine vaccines, also codeveloped with NIAID, targets Middle East respiratory syndrome (MERS), a disease caused by a different but similar coronavirus that occasionally infects people in the Middle East. Tested only in animals so far, the MERS vaccine relies on a protein on the viral surface called the spike. In theory, all the team needs to do is swap in the genetic sequence for 2019-nCoV’s spike to make the new product. They now have lot of information about how to make the spike. The MERS spike protein produces stronger immune responses when it’s in a “stabilized” conformation, and they have tweaked the mRNA accordingly. It hopes to apply the same trick to 2019-nCoV. Moderna Inc. partnership with NIAID using its mRNA platform . Funded by CEPI. Researchers at the U.S. National Institute of Allergy and Infectious Diseases, working with the Cambridge, Mass.–based biotechnology company Moderna, are developing a messenger RNA, or mRNA, vaccine that will stimulate the body to produce vaccine components. Messenger RNAs are copies of protein-making instructions encoded in the DNA of genes. Cellular machinery reads the mRNA instructions to build proteins. Scientists have selected portions of SARS-CoV-2 that may spark a vigorous immune reaction against the virus. The mRNA vaccine will tell human cells which viral proteins to make. They’re literally giving the cells a genetic code of our vaccine design, delivered as RNA that will tell cells, ‘Hey, make this protein. Those proteins — wouldn’t say which viral proteins — will then prod the immune system to make antibodies to protect against the virus. Since the body does all of the protein-production work with the mRNA vaccine, researchers can skip the time-consuming and costly step of manufacturing vaccine proteins. This strategy could be used to design vaccines against future coronaviruses or other emerging infectious diseases. Thus a universal strategy has been developed which helps to quickly deploy a vaccine if another novel coronavirus should pop up. Other mRNA vaccines against MERS and other diseases are still in the testing phase. mRNA vaccine could be ready for initial safety testing within months,but the researchers have yet to find a pharmaceutical company to manufacture the large quantities of mRNA doses that would be necessary for use by the general public. Experience with MERS vaccine is one example of just how long it typically takes to make sure a vaccine is safe and effective. Initial safety testing of the MERS vaccine was conducted in a Phase I clinical trial from February 2016 to May 2017. There were no serious side effects among the 75 healthy adult participants, the researchers. The vaccine moved into a Phase II trial in August 2018 to test safety in a larger number of people and determine whether the vaccine spurs the immune system to make protective antibodies. That trial is expected to wrap up later this year. Even if everything goes swimmingly, the MERS vaccine must still pass Phase III safety and effectiveness testing before being considered for approval by the U.S. Food and Drug Administration. It’s the same gauntlet that all new vaccines and drugs must run.
4. CureVac : A biotechnology company, for its RNA vaccine platform to SARS-CoV-2 — CEPI has called out for additional vaccine development proposals. On January 31, CEPI announced that it would work with CureVac AG, based in Tübingen, Germany, to develop another mRNA vaccine targeting the novel coronavirus. CureVac was already in the midst of a three-year, $34-million award from CEPI to develop an mRNA printer capable of producing thousands of doses of mRNA vaccine encapsulated in lipid nanoparticles.
CureVac is simultaneously producing different candidate vaccines that they’ll test in mice soon and making corresponding candidate vaccines that are of the quality for clinical studies in humans. For situations like this one — where you have an outbreak of something that is brand new . . . that was not known to infect humans before — you can then immediately take the code and use the platform that CureVac has to quickly make a vaccine against that virus. They just need to make messenger RNA, so that is an advantage in an outbreak situation. The CureVac team is choosing the viral targets for its mRNA vaccine based on past success. A study the team did in mice for testing a MERS vaccine showed that the technology did induce antibodies against the MERS coronavirus, so they’re starting with what worked then. And to move more quickly, they’re doing things in parallel that they normally would do sequentially. They’ve produced the different candidate vaccines that they’ll test in mice soon, but they are also simultaneously making corresponding candidate vaccines that are of the quality for clinical studies in humans. They are making several different candidates because of course they cannot predict exactly which one will be the best. They will likely end up throwing out some of their options, but acting in parallel will help them to move into Phase 1 clinical trials as early as the beginning of summer. Then, they might have an idea about whether the vaccine induces an immune response by the end of the summer. It’s not predictable whether the novel coronavirus will spread even further, fade away as SARS did, or perhaps become seasonal like the flu. In the case of a seasonal virus, researchers might be able to take more time, on the order of years, to develop a vaccine. It depends how this disease develops and how this epidemic develops. That will guide how authorities and developers will bring this to the population. Cyre Vac’s team has shown for other viruses that very low amounts of mRNA packaged in nanoparticles and injected into mice are translated into protein that is able to induce a functional immune response. This makes it very hopeful that we would be able to also produce large quantities of the vaccine. If this is a global health threat and you need to vaccinate large parts of the population, you need to have lots of vaccine. It is a lot of work, but it is important and people are dying.
5. Regeneron : Vaccines help keep people from getting infected with disease-causing organisms but may not help once someone is already infected. But a shortcut to getting protection — a shot of the protective antibodies themselves — may both prevent infections and treat them. People who have recovered from infections retain antibodies in their blood against the virus or bacteria that caused the illness, often for years or decades.
Such antibodies may give some protection when the person encounters a similar infectious organism later on. But, crucially, these antibodies can also protect others. And quickly. It can take weeks to months for vaccines to prod the immune system into making protective levels of antibodies. Ebola vaccines, for example, take at least a week to stimulate antibody production, but shots of antibodies offer immediate protection. In studies conducted by other researchers, blood serum containing protective antibodies taken from people who had recovered from Ebola helped infected people recover from the disease. Doctors and scientists in China have already begun using blood plasma from people who have recovered from COVID-19 to treat people who are ill with the disease. Scientists at Regeneron’s infectious disease labs in Tarrytown, N.Y., are working to develop antibodies to combat the new coronavirus in people. But giving people antibodies from survivors doesn’t always work. Regeneron and other companies have developed antibodies that can more reliably offer protection. The company is already testing antibodies against Ebola and the MERS virus. Clinical studies and laboratory work with the company’s MERS antibodies suggests that they can help protect against infection and treat established infections. The company is now developing antibodies against the new coronavirus. For instance, the team has learned more about which viral proteins and parts of proteins make the best antibody targets. Proteins on the surface of the virus that are needed for infection, such as the spike protein, are generally the best bets. Regeneron researchers have made SARS-CoV-2 proteins in the lab and injected them into mice that have human versions of antibody-producing genes. These “humanized mice make fully human antibodies, and could provide a ready supply. As soon as those antibodies are available, the company hopes to test their efficacy against the virus in the lab. If that works, safety testing in animals and people may start soon. The team also hopes to work with people who have recovered from COVID-19 to get antibody-producing cells from their blood. But, harvesting antibodies from people isn’t something that can be easily scaled up. Still, despite the rapid reaction of these and other scientists, vaccine and antibody protection for most people is still far off. In an acute situation, you’re not just going to pull a vaccine out of your pocket. If the current outbreak proves to be “really bad,” the FDA may be able to authorize emergency use of promising vaccines that haven’t completed full safety and efficacy testing. But researchers won’t know for at least six months whether any of the vaccines in development help against SARS-CoV-2. Other strategies to fight the new virus, including repurposing existing drugs used against other diseases, including HIV and hepatitis C, are also under way. But there’s no clear winner yet among those candidates. For now, people exposed to the virus must rely on their own immune systems and supportive care from doctors and nurses to fight off the disease Right now scientists are trying to accomplish something that was inconceivable a decade ago: create a vaccine against a previously unknown virus rapidly enough to help end an outbreak of that virus. Typically, making a new vaccine takes a decade or longer. But new genetic technologies and new strategies make researchers optimistic that they can shorten that timetable to months, and possibly weeks — and have a tool by the fall that can slow the spread of infection.
6. Johnson & Johnson has also announced its participation in vaccine development, using its adenovirus platform.
7. Imperial College London : Researchers here have developed a vaccine that’s already being tested in animals, and vaccine efforts are also reportedly underway in China.
8. GlaxoSmithKline : Another large pharmaceutical company, recently announced a partnership with CEPI to offer access to anyone who would like to use its adjuvant platform (adjuvants are components that can be added to vaccines to increase the generation of an immune response).
9. University Of Hongkong : Finally, adding its name to the list, the University of Hong Kong also announced it already had a vaccine, designed from a modified influenza virus vaccine.
CEPI has also launched a call for proposals to develop new vaccines against the novel coronavirus, open to all organizations meeting its criteria and in possession of a readily available platform.
Once candidate vaccines are available, researchers will test them in animals to see whether they are safe and produce an immune response. If so, companies will have to receive regulatory approvals to launch phase I human trials, which test safety and immune responses in small numbers of volunteers who are not at risk of the disease. In the case of the U.S. Food and Drug Administration, approval typically takes 1 month. NIAID already has a vaccine trial network in place that plans to stage the phase I study of the Moderna vaccine; NIAID expects the trial could start within 3 months. In parallel to the human trials, researchers will want to test the vaccine’s ability to protect animals intentionally exposed to the virus. That will require engineering a mouse model or finding another animal species — likely monkeys — that scientists can reliably infect with 2019-nCoV. Its like building the airplane as we’re flying. In the best-case scenario, the Moderna vaccine will perform well in phase I studies and be ready for larger, real-world efficacy tests in humans by summer. But previous efforts to race forward new vaccines during epidemics have hit unanticipated speed bumps. Even when experimental vaccines work in clinical trials, mass producing them quickly is inevitably a huge challenge. If Moderna devoted all of its vaccine manufacturing capabilities to one product, it could make 100 million doses in a year. Inovio can only produce 100,000 doses a year now, but is “actively speaking with a larger manufacturer which could increase their output to “multimillion” doses. The Queensland team says it could make 200,000 doses in 6 months. None of that even comes close to what might be needed to protect the world’s population in the worst-case scenario. But if the new coronavirus is seasonal in nature, as many respiratory viruses are, time might be on the vaccine makers’ side. Influenza, for instance, in most of the world typically transmits in winter and disappears in summer. If [2019-nCoV] behaves anything like flu, there will be seasonal transmission and then it will go down and there will be a recrudescence in the fall. So it could be even 1 year down the road before we see a large wave of disease. And it could be that a vaccine then plays a role in a timely fashion.” Widespread infection in populations — which may be happening in Wuhan, China, now — can also lead to lasting immunity in many people, reducing the need for a vaccine. The preparation of the vaccine is ultimately a precautionary measure. Nobody knows what’s going to happen. All are hoping we’ll never need this vaccine.
Beating vaccines to the punch
That new design relies on a relatively new approach to vaccine creation, one that the researchers used to develop the MERS vaccine. Traditional vaccines are composed of weakened or killed forms of viruses or parts of viruses, including purified proteins. When injected into a person, the immune system recognizes the virus as an invader and produces antibodies to stave off future invasions. But growing enough debilitated viruses or purifying enough proteins to make vaccine doses for millions of people can take months or even years.
So companies have developed ways to make vaccines much more quickly. For their SARS-CoV-2 vaccine, scientists convert the virus’s RNA into DNA and select pieces of the virus that computer simulations have suggested will prod the immune system into making antibodies. Those selected bits of DNA are then inserted into bacteria, which produce large quantities of protein snippets to be used in the vaccine. This approach drastically shortens the time it takes to make a vaccine. A traditional vaccine takes two to three years to develop. This new method takes three hours to design and about a month to manufacture.
Tests have started in animals at the beginning of February and hopes to begin safety tests in people by early summer.
Even so, vaccine is still at least a year away from being widely used. As the number of cases of the novel coronavirus disease, or COVID-19, continues to rise, several other groups are also racing to develop vaccines and therapeutics that take nontraditional approaches to fight the virus.
Issues and solutions
But what do these platforms mean? Why are so many different organizations working towards the same goal of developing a vaccine against one pathogen? Wouldn’t it be easier if everyone worked together, instead of trying such a wide variety of approaches? The answers to these questions are not so simple.
Vaccine platforms are tools that scientists can use to develop a new vaccine, using a similar system to previously successful approaches. For example, one well-known and straightforward approach is the “inactivated platform,” where the pathogen is safely replicated in laboratories, inactivated and then administered as a vaccine.
Although these platforms use different approaches, they all have the same overall goal of training the immune system of the vaccinated individual to quickly recognize a pathogen inside the body.
So why are there so many different platforms? Well, each platform has its own advantages and disadvantages. Some are easier to mass produce, some are known to induce fewer side effects, and some are just better at training particular aspects of the immune system.
The human immune system is divided into two major arms: innate and adaptive. Our innate immune system is non-specific and provides an immediate, but limited level of protection against a foreign intruder inside the body. The adaptive immune system can target a specific pathogen, but needs time to develop its full effect, about 21 to 28 days following infection, or vaccination. The adaptive side can be further sub-divided into humoral and cellular immunity.
With new pathogens like SARS-CoV-2, scientists don’t know which sub-division of the immune system will provide protection, so they aren’t certain which platform will produce the most successful vaccine.
What are scientists doing then ?
Vaccine design looks simple on paper, but making it work all the way to human use is a whole other story.
Currently, scientists are working on identifying which parts of SARS-CoV-2 they can use in their vaccines. These parts have to be carefully selected, because they need to mimic what a real infection would look like to our bodies. This has to be done in conjunction with selection of an appropriate vaccine delivery method: the platform that will be used.
Coronaviruses, like MERS CoV seen here, are named for their appearance under a microscope: projections give the edges of these viruses a characteristic corona, or crown-like shape.
For ethical reasons, once a vaccine candidate is available, it needs to undergo safety and efficacy testing in animals. Not all laboratory animals are susceptible to infection in the same way as humans. This is why scientists are also working to identify an animal model suitable for evaluating candidate vaccines. At this point, many months and tens of thousands of dollars have been invested in vaccine development.
Once animal trials are satisfactory, the vaccine can be administered to humans in a clinical trial to evaluate the vaccine’s safety and efficacy. This means additional months to years (if not decades), and millions of dollars in investment.
The last steps are often out of the scientists’ hands. The vaccine must be registered and receive regulatory approval, produced at large-scale and distributed. Although these steps take only a few lines to list here, they can take years to actually achieve.
On the other hand, health experts tell us over and over again that if we’re lucky and everything goes well, we could have a safe and effective vaccine in about a year. It remains to be seen at what stage of the process we will be in early 2021. If China has managed to build a 1,000-bed hospital in 10 days to counter the spread of the epidemic, who knows what can be achieved in a year on the vaccine side.
What’s the urgency?
“Vaccines are really our most successful tool to prevent an infectious disease.
It used to take a long time to make vaccines, because scientists had to isolate and grow the virus in the lab. But now, it’s possible to skip that step altogether and build a vaccine based on a virus’ genetic sequence.
Chinese scientists made that genetic sequence from the new coronavirus public in early January, just weeks after the first infections with the virus were reported. That prompted several labs to start work on building a vaccine.
Vaccines work by teaching an individual’s immune system to recognize an invading virus and neutralize it. This vaccine is called DNA vaccine.
They’ll first turn pieces of the new coronavirus’ genetic code (which is RNA) into complementary snippets of DNA. These snippets will then be injected into someone’s skin, where they will be taken up by skin cells. The skin cells will then turn those DNA sequences into proteins identical to the ones a virus would produce, and those will be what “teaches” the immune system to recognize the new virus.
Researchers are in the process of determining which viral sequences produce the best “teachers.”
This isn’t researchers first stab at rapid vaccine development. They have been working on a vaccine for Ebola after an outbreak of that virus in 2014.
Including the initial time needed for animal testing and human safety testing, researchers are able to go from no vaccine to a vaccine tested in the clinic in about 18 months — 15 to 18 months. They also made a vaccine against the coronavirus that causes Middle East respiratory syndrome, after an outbreak in South Korea. And we were able to design and develop and move into the clinic in 11 months.”
Its being hoped that the researchers would be able to halve that time with the vaccine they are making against the new coronavirus.
There were a number of enlightened global public health leaders who said, ‘You know, that shouldn’t happen. We should have some kind of an organization to develop vaccines against epidemic diseases. Even in the rosiest of scenarios, once the vaccine is in hand, it still needs to get to the people who need it, and that takes time — at least weeks to months, depending on the urgency.
Naturally, public health officials would like to have a vaccine as soon as possible. If the coronavirus outbreak pattern is anything like those of flu outbreaks, it will tend to taper off when the weather gets warmer and pick up as winter approaches and people spend more time indoors.
Scientists are moving at record speed to create new coronavirus vaccines — but they may come too late
In the stock pandemic movie, scientists are frantically working on concoctions to stop the spread of a newly emerging virus — and by the end, voila, they succeed and save the world. In the real world, vaccines played limited, if any, roles in slowing the Zika epidemic that walloped Latin America in 2016, the devastating 2014–16 West African Ebola epidemic, and the pandemic flu that began to circulate in 2009. The shots just weren’t ready in time.
This time, with infections of a novel coronavirus exploding in China — case numbers soared to more than 2700 the past 24 hours — and racing around the world, scientists contend they are better prepared than ever to produce a vaccine at Hollywood speed. Of course, the 2019-novel coronavirus (2019-nCoV), as it is now dubbed, has a solid lead in the race, and by the time a vaccine proves its worth in a clinical trial and manufacturers scale up production, it once again may be too late to make a significant dent in the course of the epidemic. But scientists hope they can make a difference.
Nobody knows what’s going to happen. We’re all hoping we’ll never need this vaccine.
Look to messenger RNA encased in nanoparticles, DNA plasmids, molecular clamps, and other approaches as they rush to design a vaccine against the new coronavirus.
The Chinese Center for Disease Control and Prevention reported on February 20 that the novel coronavirus illness known as COVID-19 has now infected nearly 75,000 people and that the number of fatalities in China has doubled since February 11, from 1,016 to 2,118. Amid uncertainty about the course of the outbreak, researchers in academia and industry are using a variety of approaches in their urgency to develop a vaccine that will work to contain the virus.
The need for speed
Another challenge to vaccine development is that the degree of immune response can vary, and it’s not always clear what type of immune reaction will benefit people during infections. Previous work showed that levels of neutralizing antibodies present in MERS patients did not necessarily correlate with the degree of killer T cell responses or outcomes. Because little is known about COVID-19, it’s not clear yet what readouts will best predict vaccine success.
“It’s a great idea to pursue multiple strategies and platforms because we really don’t know what will work best,” Roper says. As such, there are numerous other vaccine endeavors, including testing already existing MERS vaccines to determine their effectiveness for the new coronavirus and a vaccine candidate developed in a collaboration between scientists at NIAID and Oxford University.
With an increasing number of confirmed cases in China and 24 other countries, the COVID-19 epidemic caused by the novel coronavirus (now known as SARS-CoV-2) looks concerning to many. As of Feb. 19, the latest numbers listed 74,280 confirmed cases including 2,006 deaths. Four of these deaths have occurred outside of mainland China: one each in the Philippines, Japan, Hong Kong and France. The case in France is the first COVID-19 death outside of Asia.
The World Health Organization (WHO) declared on Jan. 30 that the outbreak constituted a Public Health Emergency of International Concern.
In light of these events, health experts around the world are now divided as to whether this event will become a pandemic, or whether it will be possible to contain transmission of this virus.
Vaccination consists of stimulating the immune system with an infectious agent, or components of an infectious agent, modified in such a manner that no harm or disease is caused, but ensuring that when the host is confronted with that infectious agent, the immune system can adequately neutralize it before it causes any ill effect. For over a hundred years vaccination has been effected by one of two approaches: either introducing specific antigens against which the immune system reacts directly; or introducing live attenuated infectious agents that replicate within the host without causing disease synthesize the antigens that subsequently prime the immune system.
Recently, a radically new approach to vaccination has been developed. It involves the direct introduction into appropriate tissues of a plasmid containing the DNA sequence encoding the antigen(s) against which an immune response is sought, and relies on the in situ production of the target antigen. This approach offers a number of potential advantages over traditional approaches, including the stimulation of both B- and T-cell responses, improved vaccine stability, the absence of any infectious agent and the relative ease of large-scale manufacture. As proof of the principle of DNA vaccination, immune responses in animals have been obtained using genes from a variety of infectious agents, including influenza virus, hepatitis B virus, human immunodeficiency virus, rabies virus, lymphocytic chorio-meningitis virus, malarial parasites and mycoplasmas. In some cases, protection from disease in animals has also been obtained. However, the value and advantages of DNA vaccines must be assessed on a case-by-case basis and their applicability will depend on the nature of the agent being immunized against, the nature of the antigen and the type of immune response required for protection.
The field of DNA vaccination is developing rapidly. Vaccines currently being developed use not only DNA, but also include adjuncts that assist DNA to enter cells, target it towards specific cells, or that may act as adjuvants in stimulating or directing the immune response. Ultimately, the distinction between a sophisticated DNA vaccine and a simple viral vector may not be clear. Many aspects of the immune response generated by DNA vaccines are not understood. However, this has not impeded significant progress towards the use of this type of vaccine in humans, and clinical trials have begun.
The first such vaccines licensed for marketing are likely to use plasmid DNA derived from bacterial cells. In future, others may use RNA or may use complexes of nucleic acid molecules and other entities.
Is there a vaccine under development for the coronavirus?
Was work underway on this particular strain? How do scientists know when to work on a vaccine for a coronavirus? What does this work involve, and when might we actually have a vaccine? Can humans ever be safe from these types of outbreaks?
Work has begun at multiple organizations, including the National Institutes of Health, to develop a vaccine for this new strain of coronavirus, known among scientists as 2019-nCoV. Scientists are just getting started working, but their vaccine development strategy will benefit both from work that has been done on closely related viruses, such as SARS and MERS, as well as advances that have been made in vaccine technologies, such as nucleic acid vaccines, which are DNA- and RNA-based vaccines that produce the vaccine antigen in your own body.
Was work underway on this particular strain?
No, but work was ongoing for other closely related coronaviruses that have caused severe disease in humans, namely MERS and SARS. Scientists had not been concerned about this particular strain, as we did not know that it existed and could cause disease in humans until it started causing this outbreak.
How do scientists know when to work on a vaccine for a coronavirus?
Work on vaccines for severe coronaviruses has historically begun once the viruses start infecting humans.
Given that this is the third major outbreak of a new coronavirus that we have had in the past two decades and also given the severity of disease caused by these viruses, we should consider investing in the development of a vaccine that would be broadly protective against these viruses.
What does this work involve, and when might we actually have a vaccine?
This work involves designing the vaccine constructs — for example, producing the right target antigens, viral proteins that are targeted by the immune system, followed by testing in animal models to show that they are protective and safe.
Once safety and efficacy are established, vaccines can advance into clinical trials in humans. If the vaccines induce the expected immune response and protection and are found safe, they can be mass produced for vaccination of the population.
Currently, we lack virus isolates — or samples of the virus — to test the vaccines against. We also lack antibodies to make sure the vaccine is in good shape. We need the virus in order to test if the immune response induced by the vaccine works. Also, we need to establish what animals to test the vaccine on. That potentially could include mice and nonhuman primates.
Vaccine development will likely take months.
Can humans ever be safe from these types of outbreaks?
We expect that these types of outbreaks will occur for the foreseeable future in irregular intervals.
To try to prevent large outbreaks and pandemics, we need to improve surveillance in both humans and animals worldwide as well as invest in risk assessment, allowing scientists to evaluate the potential threat to human health from the virus, for detected viruses.
We believe that global action is needed to invest in novel vaccine approaches that can be employed quickly whenever a new virus like the current coronavirus — and also viruses similar to Zika, Ebola or influenza — emerges. Currently, responses to emerging pathogens are mostly reactive, meaning they start after the outbreak happens. We need a more proactive approach supported by continuous funding.