Can We Really Develop a Safe, Effective Coronavirus Vaccine?

(Posted on Thursday, April 9, 2020)

In the event of any infectious disease outbreak, our minds turn to vaccines—and they do so for good reason. They’re safe, relatively expensive and have worked well for diseases including smallpox, polio, yellow fever, and, most recently, Ebola.

Will a vaccine come as easily for the novel coronavirus? The answer is maybe yes, maybe not. The “maybe yes” comes from the observation that in animal studies, coronaviruses stimulate strong immune responses, which seem capable of knocking out the virus. Recovery from COVID-19 may be in large part due to effective immune response. The “maybe not” comes from evidence just as strong, at least with earlier SARS and MERS viruses, that natural immunity to these viruses is short-lived. In fact, some animals can be reinfected with the very same strain that caused infection in the first place.

This raises more crucial questions with equally ambiguous answers. If a vaccine does prove to be effective, would it be effective for long? At this point, we can’t be sure. How long will it take to develop in the first place? We can hope, but we can’t be certain that it will be developed rapidly.

To understand this better, it’s important to understand how the body protects itself from invading organisms.

HOW YOUR BODY PROTECTS YOU FROM DISEASE

Certain physical and chemical barriers—skin, mucus, stomach acid—protect the body from infection around the clock. The first line of defense is innate immunity, an immediate and nonspecific immune response to the multitudes of foreign viruses and bacteria, or pathogens, we encounter every hour of every day. This includes defensins, the ancient antimicrobial proteins that mobilize cellular pathways in the fight against pathogens, and macrophages, the white blood cells that scavenge and devour all things foreign. The ultimate goal of an innate immune response is to be broadly effective. In this regard it usually succeeds, but not always.

The second line of defense is adaptive immunity, whereby the body develops a long-lasting protective response specific to what it has seen before. It weaponizes two branches of the immune system: antibody-producing B cells, and T cells that attack and kill invading microorganisms or cells affected by those microorganisms. In many cases adaptive immunity to a disease is long-lived—sometimes lasting a lifetime, often lasting 10 years or more. Other times the immune response is short-lived, which appears to be the case in early experiments with the novel coronavirus.

Not everyone can bear to ride out the two to eight weeks it takes for adaptive immunity to phase into completion—which is where vaccination comes in. Vaccines prevent disease by simulating infection, teaching the immune system to recognize, remember and fight a given pathogen before actual infection occurs. Rather than unleashing virulent organisms into the body, a vaccine builds immunity using antigens, the virtually harmless molecules that dwell on pathogenic surfaces. Antigens are foreign enough to trigger antibody production, but not dangerous enough to cause disease. Thanks to vaccination, what the body would normally learn the hard way—unexpectedly, painfully, at great cost—it can absorb under controlled conditions with relative ease.

TYPES OF VACCINES

There are many ways to develop a vaccine that successfully deters infectious disease. The first to be invented, the smallpox vaccine, used a live vaccinia virus—one similar enough to the original infectious agent, but not quite. Unlike its disease-causing counterpart, which killed about 300 million people in its heyday, the vaccinia virus caused only mild symptoms in healthy patients. This method can be replicated by identifying a “lookalike” virus that triggers the desired immune response without actually inflicting disease.

An attenuated strain of the virus, used to develop the yellow fever vaccine, is another option. Because the virus is still alive, albeit weakened, it gives the body a lasting education on how to neutralize it. The protective immunity that results could last decades. The main problem with this kind of vaccine is that not everyone has an immune system healthy enough to handle the live virus, no matter how feeble it has become.

In killed vaccines like the polio vaccine, the virus has been inactivated and thus cannot replicate itself, meaning several doses usually must be administered over time.

Subunit vaccines, such as those available for hepatitis B and the human papillomavirus (HPV), inject particular parts of the virus into the muscles. They are usually administered with adjuvants, the booster shots that strategically flood the injection site with immune cells by causing inflammation. Unlike other vaccine types, which can cause complications or even death in people with chronic immunodeficiencies or other comorbidities, nearly everyone can withstand the immune response triggered by a subunit vaccine.

To securely deliver the viral pieces that constitute a subunit vaccine, scientists purify protein compounds and insert them into a harmless virus, one destined not to survive a perilous journey through the human body. Known as viral vectors, these were used to create the Ebola vaccine. In the case of the novel coronavirus, for instance, the adenovirus vector would make an apt choice.

For many years, biotech companies have tried unsuccessfully to produce genetic vaccines, which use genetic code in lieu of the actual virus or its individual parts.

One prominent COVID-19 vaccine candidate is based on RNA, which the virus uses as its genetic code; it’s unproven as yet. Because we’re in the area of the unknown, we don’t know which vaccine type will work—and the best strategy is to try them all, mounting a massive effort that is fortunately already underway.

WHY VACCINE DEVELOPMENT TAKES SO LONG

Why does Anthony Fauci say that it could take 18 months to produce a safe, fully functioning vaccine? The difficulty is finding a vaccine that works against a very particular disease, on the one hand, and for all of humanity on the other. This is why vaccine development normally proceeds at a glacial pace compared to other pharmaceutical products—not for lack of trying or innovation, but because safety must be proven beyond a shadow of a doubt.

Therapeutic drugs are generally prescribed to sick people as needed; vaccines are generally given to healthy people en masse. It takes a couple days for scientists administering experimental treatments to hospitalized coronavirus patients to determine safety and efficacy; for those injecting vaccines into as yet unaffected test subjects, it could be years. Add the multipronged challenge of manufacturing and distributing a packaged good in a volatile global marketplace, factor in an estimated hundreds of millions of dollars in expenses, and voilà—you’ll see why many experts doubt we’ll have a COVID-19 vaccine as early as this fall.

We know that some antibody responses can actually make a disease worse. This proved to be the case most recently for the dengue virus in the Philippines, and there is some hint that issues of this sort will arise with the novel coronavirus. If a vaccine is to be administered to a sizable portion of the human population, it falls on us to proceed with the utmost caution. We must still move as fast as we can with as many resources as we can, but we must do so carefully—or risk exacerbating the spread of the current pandemic.

We need to rigorously test the dozens of vaccine candidates in the running to find one that works, and that will take some serious funding. On average, it may cost $25,000 or more per participant to put a vaccine through clinical trials. It may also take tens of thousands of participants to ensure that a vaccine candidate is effective and safe. That means it would cost upwards of $250 million just to recruit people for a single vaccine candidate. Multiply that $250 million by 10—the minimum number of vaccines, in my view, that must reach this stage—in addition to the costs of research and developing a manufacturing process, and the sum total could be somewhere in the neighborhood of 10 billion.

Even $10 billion would be a low price to pay for developing a means to stop a pandemic that is paralyzing economies around the world. No matter how much money developing a viable vaccine takes, it will be worth it. We can’t afford not to.

Read full article on Scientific American

Originally published in Scientific American (April 6, 2020)