The invisible killer

Who would have thought that the next world war would be against an invisible enemy. An enemy we cannot see and that outnumbers us by the trillions. Viruses are a strange lot. They are essentially organisms that contain nucleic acid and are surrounded by a coat of protein. They cannot be seen by an ordinary light microscope. They need a living cell to replicate. Without a host they are powerless. When viruses attack, the numbers are incredulous. Each infected cell during the flu produces 10,000 new viruses. The total number of viruses in your body can rise to 100 trillion in a few days, dwarfing the entire human population.

It is a fight for survival. We have two approaches to winning this war. One is to treat the infected, which at 2.3 million is a small proportion of the 7.8 billion worldwide population. The second is to prevent infection in the non-infected vulnerable population. That is where vaccines come into play. A vaccine uses whole or part of the virus to provide active acquired immunity. The first vaccination was done in 1796 by Edward Jenner, who showed you could develop immunity by inoculating material obtained from the hand of a milkmaid into an eight-year-old boy. He subsequently exposed the boy to small pox. The boy was unaffected and the concept of immunity was established.

The virus that causes Covid-19, SARS-CoV-2, has characteristic spikes that protrude from its surface—this is referred to as the S protein. A spike locks onto a cell receptor. The receptor then folds and the spike drills open the cell wall, and injects the viral genetic material into the cell. The genetic material then instructs your cell to produce different parts of the virus, allowing it to reproduce.

There are six types of vaccine candidates. The first two (first generation) are live attenuated or inactivated vaccines that generally involve the whole virus weakened or inactivated. This is how most vaccines like polio, measles and types of flu vaccine are made. The next type is a recombinant vaccine (second generation), wherein antibodies are stimulated to the surface protein of the virus. An example of this vaccine is HPV (human papillomavirus) vaccine. In the instance of SARS-CoV-2, the vaccine will work against the spike protein on the virus cells, preventing attachment of the virus to the cell. The last three (third generation) are the latest version of vaccines and are called DNA, mRNA and vector vaccines. They all work on the principle of getting a piece of the genetic virus code into a cell. You can use either mRNA, DNA or another virus—in this case, it is the virus that causes the common cold (adenovirus). Once the material enters the cell, it instructs our cells to make parts of the virus, which by themselves are harmless, but gives a chance to the body to get exposure and form antibodies.

The development of vaccines is complicated, but during a pandemic, multiple phases are being done simultaneously to speed them up. There is a pre-clinical stage, where vaccines are tested in animals. Phase 1 trials are to make sure a vaccine is safe. Phase 2 trials look to see that an immune response in humans does occur, and Phase 3 trials evaluate whether it actually prevents disease in large populations. Once Phase 3 trials are confirmed, they go to the Food and Drug Administration for approval. Only then do they start the process of mass manufacturing and mass vaccinations. The whole process generally takes about 12-18 months. There are 70 vaccines in the works. The top three vaccine candidates all code for the spike protein and stimulate the body to form antibodies against it.

On December 31, as the world was celebrating the beginning of a new year, the Chinese authorities alerted the WHO about a pneumonia in Wuhan of an unknown cause. Working at breakneck speed, Chinese scientists posted the first sequences of the soon-to-be SARS-CoV-2 genome online on January 11. The very same day, Inovio Pharmaceuticals downloaded the genome and began designing a DNA vaccine over the weekend. They started their clinical trial in early April, but were already behind the mRNA vaccine from Moderna along with the National Institutes of Health in the US and an adenoviral vector vaccine in China by CanSino Biologics. The good news with third generation vaccines is that they are gene-based vaccines and do not require complex viral cultures. The downside is that we do not know if they work. There are no approved mRNA or DNA vaccines, and they have never been tested in a large clinical trial. The vaccine from Oxford University is an adenovirus vector vaccine and the BioNTech/Pfizer vaccine is an mRNA vaccine. They launch Phase 1 trials on April 23. To top off the uncertainty, even if we develop a vaccine and go through all the clinical trials, the virus may mutate, necessitating us to start all over again. Vaccines are a tough business, we will be lucky if one of these 70 candidates succeeds.

There are viruses everywhere. We cannot hide from them forever. Scientists and governments are throwing everything they have, both intellectually and financially at this problem, but realistic solutions are going to take time. While we wait, we have to figure out what amount of risk we as a population are willing to take. The truth is there is risk and death all around us—cancer, heart disease, accidents, the list is endless. We are all going to die at some point, not at our time and place of choosing. The bigger question is, how do we want to live.

—The writer is chief of staff, Florida Hospital Memorial Medical Center, Daytona Beach, the US.