Covid-19 Vaccine

Just how severe is Covid-19?

In most people, their immune system is quite capable of dealing with the virus that causes Covid-19. That is why they do not get sick.

Those that do get sick, in most cases their immune system eventually rids the body of the virus. In theory, an immune system forewarned by a vaccine should be able to do a better and quicker job of fighting the virus.

Older adults and people of any age with underlying health conditions, such as diabetes, lung disease, or heart disease, are at greater risk of severe illness.

♦ By the middle of April more people were dying of Covid-19 every three days than died of Ebola in west Africa over three years.

A vaccine would not just save lives. It would protect people from getting sick and it would prevent the virus from spreading.

How quickly can the world find a vaccine?

The genetic sequence of the virus, SARS-CoV-2, that causes Covid-19 was published on January 10th. Already, there are reports of at least 86 candidate vaccines against SARS-CoV-2 being developed around the world.

♦ It seems quite likely that one or more of these efforts will lead to a working vaccine eventually.

A practical vaccine may be identified before the end of summer - perhaps more than one. But showing how well it works, finding any problems it may encounter, and manufacturing it in quantities large enough for the whole world will still take time.

A variety of approaches are being tried. Three have already started phase I trials. Phase I trials are early safety trials.

Phase I studies assess the safety of a vaccine. This initial phase of testing, which can take several months to complete, usually includes a small number of healthy volunteers. The study is designed to determine the effects of the vaccine on humans including how it is absorbed, metabolized, and excreted. This phase also investigates the side effects that occur as dosage levels are increased.

One vaccine in China has been approved for phase II trials, which are designed to find out if a vaccine can provoke an immune response strong enough to fight off the virus. CanSino Biologics, a Chinese biotechnology company has been approved for phase II trials.

It is recruiting 500 volunteers in Wuhan.

Phase II studies test the efficacy of a vaccine. This second phase of testing can last from several months to two years, and involves up to several hundred patients. Most phase II studies are randomized trials where one group of patients receives the experimental vaccine, while a second "control" group receives a standard treatment or placebo. Often these studies are "blinded" which means that neither the patients nor the researchers know who has received the experimental vaccine.

After phase II comes phase III testing, no one is even talking about that.

Phase III studies involve randomized and blind testing in several hundred to several thousand patients. This large-scale testing, which can last several years, provides researchers with a more thorough understanding of the effectiveness of the vaccine, the benefits and the range of possible adverse reactions.

♦ It is not enough that a vaccine be feasible. The vaccine must be made available around the world as fast as possible.

In terms of human welfare, what matters is making that time as short as safely possible.

The demand for a vaccine that provides reliable and safe protection to whole populations will be huge. The world currently makes over 5 billion doses of vaccines a year, of which includes roughly 1.5 billion doses of seasonal-flu vaccines.

Prestige and politics

In terms of prestige and politics, creating an effective SARS-CoV-2 vaccine will be a huge feather in the cap of the researchers, companies and nations responsible.

If the Chinese, as it could well be, develop the first vaccine it will be presented as a triumph both of Chinese science and the Chinese government.

If it is America, it would also be presented as a triumph of American greatness.

♦ A big concern is, if vaccine production capacity is constrained, the politics of who gets it may get nasty.

An optimum strategy for using limited stocks of vaccine in a way that best benefits the world would be to devote them to populations at particular risk. This is not likely to happen.

A country with a lead in vaccine manufacturing is more likely to devote its limited stocks to universal coverage for its own citizens, reasoning that not only lives but their country’s economy is at stake.

Vaccine approaches being studied

Before the days of genetic engineering, there were three ways to let the immune system get acquainted with viral antigens it needed to know about.

♦ Live-attenuated Vaccine - A strain of the virus, or a related virus, that was capable of infecting cells but had been hobbled in some way so as not to cause sickness.

This is the approach taken with many of the more common established vaccines, such as those against measles, mumps and rubella.

A live-attenuated vaccine in is being developed by Codagenix, an American biotech company, in collaboration with the Serum Institute of India.

♦ Inactivated Vaccine - A virus that had been inactivated (killed), and thus cannot cause an infection. This is how the Salk polio vaccine works. It is also the technique used for seasonal-flu shots.

Sinovac Biotech, based in Beijing, is working on an inactivated version.

♦ From blood – Antigen separated from the blood of someone who was infected and recovered. This was the original approach taken to make the hepatitis B vaccine.

Many scientists are looking at SARS-CoV-2 vaccines that consist of a single protein mass produced by adding the gene for the protein that forms the virus’s outer coat to cell cultures and in this way producing the protein in the pure form. Most of these efforts are aimed at the spike proteins that stud the virus’s outer layer. This the way hepatitis B vaccine is made these days.

Novel approaches

• Sheep-in-Wolf’s Clothing – This approach is how the Ebola vaccine works. A gene from the virus is put into another virus that is not normally harmful. It is introduced into the patient and their body fires up and produces the antibody against the virus. This is technically called a “recombinant vector” vaccine.

This approach has not been used widely in humans so it would be slower to gain approval.

The CanSino Covid-19 vaccine that has entered phase II trials is a “recombinant vector” vaccine of this type. It is a live virus engineered to express the spike protein for SARS-CoV-2 virus.

• DNA or RNA – Genetic engineering has opened the door to nucleic-acid vaccines. The idea is to introduce the gene for the antigen into the body as a piece of either DNA or RNA, a related molecule that many viruses use as a medium for storing genes.

The body’s cells then produce an immune response and manufacture the antibody for the virus the DNA or RNA is associated with.

There are two such vaccines already in phase I trials: a DNA vaccine developed by a Beijing company and one by an American company.

An RNA vaccine is being investigated by an American biotechnology company. It has recently been given permission to move to phase I testing. A number of other firms are not far behind.

Nucleic-acid vaccines have advantages and disadvantages. Their production is completely independent of viruses, making contamination highly unlikely. They should be easily scaled up.

The problem is that no DNA or RNA vaccine has yet been licensed for use in humans anywhere in the world.

Experimental DNA vaccines have produced immune responses in humans, RNA vaccines have yet to get even that far.

More work is needed

The type of the vaccine is not the only variable trials have to look at. The dose matters also. Some vaccines may need to be administered more than once. Sorting out effectiveness and dosing is one of the reasons trials need to be completed.

There are also adjuvants (chemical cofactors) that can enhance a vaccine’s effect on the immune system. No one fully understands how adjuvants work so this makes finding the best adjuvant all the more difficult and time consuming.

The immune system still holds many mysteries. The BCG vaccine used against tuberculosis, for example, seems to have a stimulating effect on the immune system that goes well beyond TB.

Four countries are running trials of BCG against Covid-19 even though no specific new antigens have been added to it.

A particular safety worry for Covid-19 vaccines is “antibody dependent enhancement.” In some diseases, and in some circumstances, antibodies can make a viral infection more damaging.

Challenge trials

This term that will undoubtedly be heard a lot more before Covid-19 is tamed.

Some researchers are pushing for speed over safety. They are pushing “challenge” trials. A normal trial would vaccinate a lot of people and then see how many get sick naturally.

Challenge trials jump the gun and deliberately expose vaccinated volunteers to the virus. The ethical ramifications of such trials are troubling.

A group of Harvard scientists recently suggested that if volunteers were young and healthy a small challenge trial might be worth the risk and the data gathered might be useful.

Profits are a motivator or not

Profits in vaccine making are low, not many Western companies find such capabilities worth the time and risk.

Almost all the pharmaceutical industry’s vaccine-manufacturing know-how is concentrated in just four companies: GSK, Johnson & Johnson, Pfizer and Sanofi.

These companies have no desire to develop vaccines for pandemics. Vaccines for diseases that then vanish are less profitable than a yearly flu vaccine.

In theory, manufacture of Covid-19 vaccines using conventional approaches could be scaled up quickly. But doing so might mean fewer regular vaccines get made.

The World Health Organization (WHO) reports that there are already unrelated shortages of vaccines for yellow fever and measles.

The seasonal nature of flu vaccinations means that those production facilities have spare capacity part of the year.

Working together

Governments have yet to coordinate their response.

Scientists are urging the G20 to try and reach some kind of consensus on vaccine production and then fund it. The G20 has in turn asked the WHO to outline a plan for the equitable distribution of the goods needed to fight Covid-19.

President Trump recently cut funding to the WHO. It seems unlikely that he will work on a coordinated effort to ramp up vaccine production and distribution for the world’s people.

Politics will likely see some people trampled underfoot in the rush to get out.