$5 vaccine against COVID-19 possible? Latest trial updates here

That means governments have taken a greater risk than biotech firms in developing and producing millions of vials before they're approved. In case the vaccine works, the vials are ready.

If they're rejected, they're binned. The private companies don't lose any money making them, so there's not much of a risk-return equation for them to figure out.

More than 150 countries are engaged in COVID-19 vaccine efforts globally, including the UAE, which kicked off Phase 3 trials on Thursday (July 16) of an inactivated vaccine (or the so-called "killed" virus platform).

Q: Would an affordable COVID-19 vaccine happen in real life?

Whether it happens in reality or not depends on the outcome of the trials, and on the text of deals signed by governments with various vaccine makers.

A global dash is on to develop and mass produce millions of doses of vaccines — using both old, proven “platforms” as well as novel ways. Earlier, one Indian vaccine maker claimed they could produce a jab against SARS-CoV-2 for $13.20.

Q: How can $5 vaccine actually happen?

One American team reportedly boasted they could partner with producers in developing countries, presumably India, to provide millions of vials for as little as $5 per vial.

The official who made that boast came from the mRNA camp. So a $5 COVID shot may not be an idle boast.

One example: a polio shot today costs $0.50.

Q: Why are governments pouring billions of dollars into vaccine development?

A vaccine is the seen as the best weapon against COVID-19. Millions of jobs have disppeared. COVID cases are still spiking globally, though in countries like the UAE, the curve appears to have flattened and on the way down.

Governments have given at least $3 billion towards COVID-19 vaccine development, using both old-and-proven ways as well as mRNA, deemed a safer, more flexible and rapid-production vaccine platform, though this claim remains unproven.

Q: What is an mRNA vaccine?

First of all, it's non-viral. Until today, all vaccines are actually viruses, or a version of it. mRNA, on the other hand, is a process that produces synthetic proteins in the body which mimics specific proteins of a pathogen. They're sort of "fake" viruses.

The three frontliners in the mRNA vaccine development – Moderna, Pfizer/BioNTech and CureVac – use mRNA for at least one or several of their vaccine candidates.

Q: How does it work?

The technique is based on deploying a tiny sequence of genetic code called "messenger RNA". When the genetic code sequence (messenger) is injected in the body, it creates specific proteins.

Using a technique that's sort of like a volume control, scientists can methodically amplify or reduce the protein characteristics, depending on the desired outcome. The proteins can then trigger the immune response.

With the endorsement of the world’s top scientists, including Dr Anthony Fauci of the US National Institute of Allergy and Infectious Diseases, cutting-edge mRNA trials have jumped to the forefront of the race to fight COVID-19.

Some developers plan to have tens of millions of doses ready before the end of the year, signing up production partners in India, including Bharat Biotech, a key vaccine supplier to the Unicef’s various inoculation programmes.

Q: Why did mRNA vaccines jump into the forefront?

Nature published a study in January 2018 highlighting the merits of mRNA vaccines. It’s a much better alternative to conventional ones: mRNA vaccines have elicited potent immunity against infectious disease targets in animal models of influenza virus, Zika virus, rabies virus and others, especially in recent years, using lipid-encapsulated or naked forms of sequence-optimised mRNA.

“They are known for their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration,” a Nature article states.

With the COVID-19 candidate vaccine, developers have announced plans to have tens of millions of doses ready before the end of the year.

Q: What’s the issue with mRNA?

Until recently, their application has been restricted due to their unstable and inefficient “in vivo” delivery of mRNA. Recent advances, however have now largely overcome the earlier challenges with this technology.

Writing for Nature, Dr Norbert Pardi, of the Department of Medicine, University of Pennsylvania, in Philadelphia, and his team cited how multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated “encouraging results” in both animal and human trials.

The key issue is that no mRNA vaccine has ever been approved for use by any government. It’s only the first time it’s being used as a vaccine against a real-life pathogen.

Q: Rapid vaccine development with mRNA: How’s that possible?

Scientists extol mRNA’s upside due to its ability to be put to widespread and rapid use. Conventional vaccine approaches (such as live-attenuated, inactivated/killed pathogens and subunit or toxoid vaccines), provide durable protection against a variety of dangerous diseases.

Despite their success, there are two major hurdles to vaccine development: Speed and safety.

When there’s a new infectious pathogens — it takes several years to develop a vaccine (5 years for Measles vaccine and an average of 8 years for the rest of 25 vaccines on the WHO list).

Q: What methods are used in vaccine production?

Vaccines are produced in various ways:

(a) “live attenuated” (virus is alive but its potency had been greatly reduced)

(b) sub-unit

(c) “killed” (inactivated) virus

(d) Toxoid

(d) DNA

(e) mRNA

In most vaccine platforms, the serum comes from the whole virus, or a version of it. It is cultured and processed/mass produced in a high-security biosafety facility.

They are then stored in vials that end up being injected into our arms (or taken orally, as in the case of the $0.50 oral polio virus, OPV). In effect, the dose injected to us (determined after extensive trials) gets us “infected”, which then triggers an immune response in our body. That’s how immunity is achieved.

After the shot, our body will just shrug off the disease-causing infection the moment we get it — often without us even know about it.

Q: What’s the main cause of vaccine production delay?

One major cause is testing. Extensive pre-clinical and clinical trials are required for any vaccine. There’s a constant war between safety/efficacy and immediacy. After trials, a vaccine must go through an elaborate process of evaluation, licensing, production and post-distribution checks.

Q: What are the key advantages of mRNA vaccine?

The portion of the “virus” being injected is a synthetic one. So it mimics only a component (like the target spike protein of SARS-CoV-2). It’s not the virus itself being used, so it’s inherently safe. Techniques had been develop to rapidly reproduce it, say experts. The use of mRNA has several beneficial features over “killed”, subunit and live attenuated virus, as well as DNA-based vaccines.

First: Safety

As mRNA is a non-infectious, there is no potential risk of infection or insertional “mutagenesis” (genetic mutations). mRNA is considered the the minimal genetic vector, therefore, anti-vector immunity is avoided, and mRNA vaccines can be administered repeatedly.

Second: Flexibility

mRNA is degraded by normal cellular processes, and its in vivo half-life can be regulated through the use of various modifications and delivery methods. This means the inherent immunogenicity of the mRNA can be “down-modulated” (or downregulated) to further increase the safety profile.

Third: Efficacy

Various modifications make mRNA more stable and highly translatable. Efficient in vivo delivery can be achieved by formulating mRNA into carrier molecules, allowing rapid uptake and expression in the cytoplasm (material within a living cell, excluding the nucleus).

Fourth: Rapid production

mRNA vaccines have the potential for rapid, inexpensive and scalable manufacturing, mainly owing to the high yields of in vitro transcription reactions.

Q: What are the recent successes of mRNA?

The mRNA vaccine field is developing very rapidly. Nature has extensively discussed current mRNA vaccine approaches and its future as a vaccine platform. Researchers cited data suggesting that mRNA vaccines have the potential to solve many of the challenges in vaccine development for both infectious diseases and cancer.

The mRNA vaccine field is developing very rapidly.

Q: Is it true Tesla is involved in mRNA technology?

Elon Musk has sent out a tweet recently stating they are working with CureVac on making "mobile molecular printers" to assist the German biotech firm in mass producing its vaccine.

The Tesla printers are reportedly designed to be used in remote locations. They would manufacture the vaccine candidate and other potential mRNA-based therapies using whatever recipe is programmed into them.

Q: What's the latest on Pfizer's mRNA vaccine?

On Tuesday (July 14), the US FDA has "Fast-Tracked" two potential coronavirus vaccines from Pfizer and BioNTech. This could speed up the regulatory process and allow them to bring their mRNA coronavirus vaccines to market more quickly.

Q: If the vaccine gets approval, how many will Pfizer produce?

Up to 100 million doses this 2020. And up to 1.1 to 1.3 billion doses by 2021, Pfizer CEO Albert Bourla told Time.

Q: When did Pfizer do Phase 1/2 trials, what happened?

Four different constructs of a vaccine created by Pfizer and BioNTech (a German biotechnology company focussed on cancer treatments) came in varying dose levels. The versions that got FDA Fast-Track approval are BNT162b1 and BNT162b2.

The Phase I/II trials of BNT162b1 conducted May 4 to June 19, 2020. In those trials, 45 people ages 19-54 were randomized and vaccinated at different doses. Some received a single, higher-dose of the vaccine. Others received two vaccinations at lower doses separated by 21 days. Nine people received placebo injections, according to early data that has yet to undergo peer review but was published on MedRxiv.

Q: What happened to the CureVac trial?

On May 14, CureVAc announced positive pre-clinical results at a low dose for its lead vaccine candidate against SARS-CoV-2. The data showed immune response was induced with high levels of virus-neutralising "titers" (VNTs) and T-cell responses.

VNTs are a major criterion supporting that the vaccine candidate has the potential to induce a strong immune response against SARS-CoV-2. CureVac has already produced large quantities of material for its vaccine candidate in its Tübingen (Germany) facility.

Its production capacity can potentially supply several hundred million doses per year, depending on the human dose defined in the clinical trials, the company stated.

CureVac is backed by Coalition for Epidemic Preparedness Innovations (CEPI), the Bill & Melinda Gates Foundation as well as from the Defense Advanced Research Projects Agency (DARPA), the US agency that invented the internet.

Q: What about Moderna mRNA-1273 candidate vaccine?

Phase 1

Moderna's Phase 1 study for mRNA-1273 is done. Interim data was announced on May 18 in pre-preprint publication. The data was peer reviewed and published on NEJM on July 14, 2020.

Phase 1 results show mRNA-1273 induced immune responses — in all of the volunteers who received it. It is the first candidate vaccine is the first US to publish results in a peer-reviewed medical journal.

Phase 1 showed that the vaccine worked: It triggered an immune response with mild side effects. 

Phase 2

In Phase 2, the clinical study is expanded and the vaccine is given to people who have characteristics — such as age and physical health — similar to those for whom the new vaccine is intended, according to the US CDC. Moderna completed enrollment of its Phase 2 study of mRNA-1273 on July 8. Therea are 300 younger adults and 50 older adults in the Phase two study.

Phase 3

In Phase 3, the vaccine is given to thousands of people and tested for efficacy and, again, for safety. Up to 30,000 people will be involved — it's the final trial stage before regulators consider whether to make the vaccine available.

Q: How many Phase 1 volunteers were involved?

Moderna's Phase 1 study included 45 healthy adults (ages 18 to 55) who received two vaccinations of the mRNA-1273 vaccine candidate 28 days apart.

Some of the volunteers enrolled in the trial at Kaiser Permanente in Seattle and others at Emory University in Atlanta.

The volunteers were separated into groups where they either received the vaccine at a dose of 25, 100 or 250 micrograms. They received their first vaccination between March 16 and April 14.

On Tuesday (July 14, 2020) Moderna's mRNA vaccine  has been found to induce immune responses -- in all of the volunteers who received it in a Phase 1 study. These early results, published in the peer-reviewed New England Journal of Medicine on Tuesday, are significant. The Moderna's mRNA-1273 candidate vaccine is the first US vaccine candidate to publish results in a peer-reviewed medical journal. It showed that the vaccine worked: It triggered an immune response with mild side effect. The vaccine is expected to begin later this month a large Phase 3 trial — on up to 30,000 people — the final trial stage before regulators consider whether to make the vaccine available.

Q: How many doses of mRNA-1273 Moderna plans to produce?

If Phase 3 goes well and their vaccine is approved, the biotech firm "remains on track to be able to deliver approximately 500 million doses per year, and possibly up to 1 billion doses per year, beginning in 2021", according to a company statement.

In the Phase 1 study, "the goal was to look at safety and then to look at immune responses," said Dr. Lisa Jackson, a senior investigator at Kaiser Permanente Washington Health Research Institute in Seattle, who was involved in the study. Early data from the study previously was released in May. After the first vaccination, adverse events were reported by five participants in the 25-microgram group, 10 in the 100-microgram group, and eight in the 250-microgram group. Then after the second vaccination, such events occurred in seven of 13 participants in the 25-microgram group, all 15 in the 100-microgram group, and all 14 in the 250-microgram group, with three of those participants reporting "one or more severe events," according to the study.

Q: When is the start of Phase 3 for Moderna mRNA-1273 trial?

Moderna expects to start Phase 3, their largest study yet of mRNA-1273 on July 27, it will be the first in the US to begin Phase 3 trials.

Q: What were the reported side effects from the mRNA shots?

Moderna

After the first vaccination, adverse events were reported by five participants in the 25-microgram group, 10 in the 100-microgram group, and eight in the 250-microgram group. Then after the second vaccination, such events occurred in seven of 13 participants in the 25-microgram group, all 15 in the 100-microgram group, and all 14 in the 250-microgram group, with three of those participants reporting "one or more severe events," according to the study.

The most commonly reported adverse events following second vaccination (in in 100-microgram group);

The events were "transient and mild or moderate in severity", according to Moderna

After the first vaccination, adverse events were reported by five participants in the 25-microgram group, 10 in the 100-microgram group, and eight in the 250-microgram group.

Then after the second vaccination, such events occurred in seven of 13 participants in the 25-microgram group, all 15 in the 100-microgram group, and all 14 in the 250-microgram group, with three of those participants reporting "one or more severe events," according to the study.

Pfizer

Pfizer stated that rost reactions peaked by two days after vaccination and resolved by the seventh day after vaccination. All who received the vaccinations developed antibodies to SARS-CoV-2, the novel coronavirus.

The preliminary data also noted that those who had two lower doses of the vaccine developed more antibodies than those who got the single higher dose.

CureVac

On June 17, CureVac received regulatory clearance to start a Phase 1 trial of its COVID-19 vaccine. On July 14, 2020, up to 4,000 people volunteered to serve as guinea pigs to help test CureVac's experimental jab.

The large volume of volunteers took the research team, which usually struggles to find willing participants for its studies, by surprise.

CureVac's Phase 1 study involves 168 volunteers. The German government earlier announced they had invested €300 million ($337 million) in CureVac to support its efforts to develop and manufacture a vaccine, known as.

No trial results are available from CureVac yet.