The Covid-19 Chronicles: Goldilocks and the 37 Vaccines

LIBERTY, freedom and independence. Three related words with different meanings to different people.

As Malaysians celebrate 62 years of independence from colonial rule on Aug 31 and upcoming Malaysia Day on Sept 16, Covid-19 reminds us that infectious diseases still threaten the basic liberties and freedoms we took for granted, such as travelling beyond the country’s borders, or breathing air unfettered by masks.

To regain some of the freedoms of life pre-Covid-19, we need a vaccine.

This simple concept of introducing the body with weakened or parts of bacteria or virus to train our immune system with memory and preparedness to fight the invading bug, have freed us from terrible infectious diseases like smallpox.

Vaccinations began in 1746 with an eight-year-old boy named James Phipps, who was given cowpox from the blisters of an infected milkmaid, exposed to smallpox, and was (fortunately) immune or protected from smallpox.

Since then, this concept has been expanded and various types of vaccines have been developed to protect humankind (and livestock) from various infectious diseases.

But compared with drugs and medicines, vaccines are very tricky things to make. Several hurdles set vaccines up for failure.

Firstly, vaccines are given to people who are not ill. Unlike drugs, which are taken when sick or suffering, there is some accepted tolerance for any unpleasant side effects, developers must show convincingly that taking the vaccine will not cause any harm.

Secondly, demonstrating that the vaccine has worked takes a much longer time. Any positive effect will not likely be appreciated by the individual who gets vaccinated, but only by the public health system after years of monitoring.

Thirdly, a vaccine closest to the virus or bacteria it tries to protect against is generally more effective, but these vaccines are also more likely to cause potential illness or adverse events.

Many vaccines are given to infants and small children (some at birth, such as the Bacillus Calmette Guerin or BCG and the Hepatitis B vaccine) amplify the risks and challenges in developing and delivering vaccines.

Because of these risks, it usually takes many years and several trials before obtaining approval. Most candidates do not even pass the preclinical phase, typically conducted for years in animals to determine safety and ability to stimulate an immune response.

After the preclinical stage, on average it takes eight years to test vaccine safety and determine appropriate doses in 10-100 (phase I) or 100-1000 people (phase II), and determine that the vaccine is protective in 10,000s of people (phase III).

Once approved, vaccines are purchased by governments and distributed through various vaccination programmes.

Previously, there were not many options of vaccines for the same disease.

But for Covid-19, there are 91 vaccines in the preclinical phase, 24 in phase I, 14 in phase II, nine in phase III, and three (controversially) approved for early or limited use.

This unprecedented global vaccine race is arguably led by China (Sinovac, CanSinoBio), Russia (Gamaleya), the United Kingdom (Oxford-AstraZeneca), and the United States (Moderna-NIH).

Besides Sinovac, the other developers mentioned are harnessing new technologies such as messenger RNA and viral vectors. The former uses synthetic genetic material tasked with delivering information to cells to produce viral proteins, and the latter uses another virus to package and deliver genetic information of SARS-CoV-2, the virus causing Covid-19.

With so many options, all with their own pros and cons, countries like Malaysia are now tasked with placing taxpayers’ money on their best bets, negotiating the vaccine that is “just right” to protect the population.

Once committing to a vaccine, governments will need to convince the masses questioning the breakneck speed at which the Covid-19 vaccines have been developed, while addressing legitimate concerns about safety.

While some of the time taken to undergo clinical trials are due to regulatory administrative processes, much of the time taken to obtain approval in a promising vaccine is the mammoth task and time it takes to show the vaccine works and does not cause serious illness in tens of thousands of people in phase III trials.

Unlike in animals and in the case of James Phipps where the invading bug is introduced by the researcher, in ethical human trials, the groups of volunteers randomised to receive the vaccine versus a placebo are observed over time to determine whether they get sick or die through natural exposure.

The developers of Covid19 vaccines must be able to demonstrate that their vaccine not only protects a high majority of people (the US Food and Drug Administration or FDA says at least 50%) compared with those who received the placebo, but also that there is not a higher occurrence of adverse events beyond a brief episode of the usual pain at injection site, or mild flu-like symptoms.

AstraZeneca recently halted phase III trials to investigate an unexpected illness in one of its volunteers; they will need to determine whether the vaccine was directly responsible for the condition.

This is not uncommon, and an important step in addressing arising vaccine safety concerns.

Even after rigorous phase III trials, monitoring remains crucial. As millions of people receive the vaccine, rare adverse events or variations in vaccine effectiveness become more apparent.

For example, the BCG vaccine, which protects against tuberculosis, is actually a group of different preparations, with different countries using different versions, some offering better protection than others.

Over time, the vaccine was deemed unprotective in adults, and additional doses (“boosters” previously given to schoolkids) were no longer given.

Despite some of these shortcomings, the BCG vaccine is also now known to provide vaccinated children protection against other respiratory bacterial infections, and is even currently being investigated for possible protection against severe Covid-19.

This was information that only became available after decades of use in millions of infants, for a vaccine made using traditional methods, against a historically prominent human disease.

One reason Covid-19 has been devastating is because it is a new disease for humans, and our bodies do not “remember” how to fight this virus. A good vaccine would give us a chance to create that memory without more people getting sick or dying.

A good vaccine will give us a fighting chance to gain some freedom from the clutches of Covid-19.

But even a good vaccine will be far from perfect, and compromises will have to be made.

That said, in the landscape of vaccine refusals and science suspicious, there should be no compromise on safety and transparency.