'Killed virus' against COVID-19: How it works

DUBAI: In the fascinating world of vaccinology, a “killed virus” is a term often used.

An alternative phrase used is “inactivated vaccine”. In other words, a “killed” vaccine is a shot that actually consists of the virus, bacteria, or other pathogens that had been grown in culture.

It’s both science and miracle. The killed virus gets injected into healthy people, who then eventually develop immunity to that same virus.

In the case of the SARS-CoV-2, the virus is methodically cultured in order to multiply, before being deliberately "killed" — as in rendered dead. That, in a nutshell, is how a killed virus vaccine works.

And it works well.

However, it’s a whole lot more complicated than that. First, this entire process must be done in high-security, top-level biosafe condition.

The “killing” of the virus is aimed to do one thing, and one thing alone: take out the virus' ability to trigger a disease.

It’s an interesting technique: their presence in the human body has — in the past, as it does today — proven to be one of the surefire ways to trigger an effective immune response.

This, however, is just one of the classical methods available to science in developing vaccines.

Q: 'Killed' and 'live' vaccine: What’s the difference?

A killed vaccine is in contrast to a “live” vaccine.

The latter uses pathogens that are still alive (but are almost always "attenuated", i.e. with reduced virulence). In other words, by definition, a live vaccine is a form of pathogen that’s still alive, but in a much weakened form.

Q: How are 'killed' vaccines done?

Here’s one fascinating thing with vaccine development: Pathogens used for killed (inactivated) vaccines must first be grown in huge numbers, literally countless billions.

But this must be done under strict biosafety conditions and close regulatory supervision. You don't want the virus to escape or go anywhere, especially via inhalation by the bio-engineers working on them. 

Therefore, in order to be grown (cultured) in a lab — and in huge numbers — the virus must be alive and actually reproduce.

One important note: The conditions for handling them must come under strict, controlled protocols.

Even the “killing” part must come under close regulatory scrutiny. The pathogen is “killed” as a means to reduce its infectivity.

When we get this vaccine, the killed version, it would presumably help our bodies build “antibodies”. In short, it would arm us with “soldiers” in our system that spring into action to kill the real pathogen when it comes — a process generally known as an “immune response”.

Q: How is it applicable to the fight against COVID-19?

Let’s say, after rigorous trials, a new vaccine has been finally approved and licensed for mass inoculation (vaccination). And that it's based on the “killed” virus platform (there are other platforms, like DNA and mRNA vaccines).

It actually means the vaccine that will go into our body will be the “killed” version of SARS-CoV-2, the same virus that causes the deadly COVID-19. But in so doing, when a live SARS-CoV-2 virus hits you from others (like your own family), there are antibodies ready, lying in wait to fight off the new invader.

This is the sort of enigma surrounding vaccines: Until today, the vaccine development techniques proven to work in billions of shots already given around the world involve growing the virus first, then “killing” it, in order to produce an antivirus.

.There are new, exciting ways of producing vaccines that don’t use this “killed” virus route

Q: How are they killed?

The virus is killed using established methods — such as heat, radiation or using formaldehyde.

Q: What are the classifications of killed vaccines?

There are different classes of inactivated vaccines, based on the method used to inactivate the pathogen.

(1) Whole-cell virus: The Who considers inactivated “whole-cell virus” (using the entire virus particle, but fully destroyed using heat, chemicals, or radiation) more effective. https://www.who.int/vaccine_safety/initiative/tech_support/Part-2.pdf

(2) “Split virus” vaccines (aka “split-virion vaccine”) are produced by using a detergent to kill the virus.

(3) “Subunit vaccines” are produced by purifying out the antigens that best stimulate the immune system to mount a response to the virus, while removing other components needed for the virus to replicate or survive or that can cause adverse reactions.

Q: How effective is each type?

Historically the “whole virus” approach toward vaccine creation and production have yielded highly effective vaccines that are safe and immunogenic.

In 2015, a study published in Clinical Infectious Diseases, states that “split-virion vaccine effectiveness was 77.8% (95% confidence interval [CI], 58.5%–90.3%) compared with subunit vaccine effectiveness of 44.2% (95% CI, −11.8% to 70.9%), giving a difference in vaccine effectiveness of 33.5% (95% CI, 6.9%–86.7%).”

Q: What’s the downside of “killed” vaccines?

Studies show that compared to live viruses, “killed” viruses tend to produce a weaker response by the immune system.

Q: What’s the solution to this downside?

To address this weakness, vaccinologists have come up with immunologic “adjuvants”, and and multiple "booster" injections may be required to provide an effective immune response against the inactivated pathogen.

This year (2020) marks 100 years of the use of adjuvants in human vaccines (since 1920). 

Q: Mono vs polyvalent vaccines: What’s the difference?

Vaccines may be monovalent or polyvalent.

A “monovalent” vaccine contains a single strain of a single antigen (example: the Measles vaccine).

On the other hand, a “polyvalent vaccine” contains two or more strains/serotypes of the same antigen (e.g. Oral polio vaccine, OPV).

Q: What are the different vaccine types?

In general, different types or “designs” are in use today, each specifically aimed to “teach” our immune system to fight off specific pathogens — and the illness they trigger.

Based on a number of factors (i.e. age and health condition of the target population, as well as vaccine platform), scientists decide which type of vaccine they will make.

These are the basic types of vaccines:

Q: What are the examples of viral and bacterial vaccines:

Examples include:

Q: What about combo (or combination) vaccines?

This is another fascinating bit in vaccine development: Some antigens are combined in a single shot that can prevent multiple diseases or that protect against different strains of pathogens causing the same disease.

One example of combination vaccine: DPT (which combines diphtheria, pertussis and tetanus antigens). These combo shots have been routine for certain age groups.

Q: Why are they combined?

Parents who need to inoculate their kids understand the value of combo shots, and must thank the scientists who developed this technique. Combining shots has helped solve practical and logistical nightmares. One benefit is that combo jabs help overcome the constraints that come with multiple injections (also consider the children’s fear of needles and pain).

Q: What are the examples of killed virus shots being developed for COVID-19?

There are currently 31 frontrunner vaccine candidates against COVID-19, based on the latest (July 6) World health Organisation (WHO) list.

Among examples of “killed” or inactivated vaccine is Sinovac Biotech Ltd’s candidates (there are three).

Sinovac said its coronavirus shot is safe and capable of eliciting an immune response from human trials, suggesting the shot's potential in defending against infection of the novel coronavirus.

Another killed vaccine candidate from China: Wuhan Institute of Biological Products/Sinopharm's vaccine, now in advanced human trials.

There are at least two more from China using this killed virus platform: One from the Beijing Institute of Biological Products/Sinopharm, the Institute of Medical Biology, Chinese Academy of Medical Sciences.

Japan’s KM Biologics Co, Ltd, is also developed an inactivated COVID-19 vaccine (still in pre-clinical stage as per WHO list). Egypt’s National Research Centre and Turkey’s Selçuk University are also in the running to develop a killed virus vaccine.

Thailand’s Chulalongkorn University is collaborating with the National Vaccine Institute and Department of Medical Sciences.

The “Thai solution”, however, is an equally interesting vaccine platform, called mRNA (messenger RNA), according to the WHO. Human trials for the Thai vaccine are slated for September, after pre-clinical trials on monkeys proved “encouraging”.

The world health body lists more than 120 vaccines against COVID-19 under development around the world.

Most of the vaccines on clinical trials, using different techniques, have proven their worth in human volunteers, sometimes several thousands coming forward to become virtual guinea pigs.

Q: Are COVID-19 cases on the rise?

Worldwide, and in many places, the answer is “yes”. Latest WHO data show 220,000 cases were confirmed in the last 24 hours (July 11) globally.

But scientists point to one upside as new cases spike: The relatively high number of new cases being diagnosed daily — 62,653 in the US alone on July 11 — would theoretically make it easier to test vaccines. It would also, as recent experience shows, increase the availability of donors for convalescent plasma therapy (from recovered patients). 

Q: What do the vaccine trials show, so far?

So far, and thankfully, no deaths had been reported among any of the healthy human volunteers after taking experimental vaccines (in different doses) against COVID-19. There were mild and expected side effects, like fever within 24 hours of taking the shot.

Q: What does it mean?

This means that, at the very least, the vaccines currently on human trials are safe.

Whether or not they’re effective — or how long the immunity given by a specific shot lasts — is quite another story.