COVID-19 ISO Insights

What are Key Considerations as COVID-19 Vaccine Development Enters Into the Stretch Run?

August 3, 2020

By: David Geller, CPCU, SCLA

It would be an understatement to say that the stakes for developing a COVID-19 vaccine are quite high. And with six vaccine candidates reportedly entering into Phase III efficacy trials, as of the end of July, optimism has appeared to grow that a vaccine could indeed be ready to be administered by the end of 2020.

However, a slew of considerations remains as the trials continue to progress. Here are just a handful:

Phase III Trials: Scientists Reportedly Monitoring for Disease Enhancement

The Wall Street Journal reports that, among other items, scientists will monitor for a phenomenon known as disease enhancement, which actually can worsen the disease it is intended to protect against; disease enhancement occurs when “immune agents act in ways that facilitate replication of the virus.”

Historically, per the WSJ, some vaccine trials for coronaviruses have coincided with disease enhancement. For example, when experimenting a vaccine on mice following the 2002 SARS outbreak, disease enhancement was recognized. Ultimately, no vaccine was ever developed for SARS.

More recently, the WSJ notes that, in 2017, some children who were vaccinated for the tropical disease called dengue ultimately came down with a severe form of the illness, potentially indicating disease enhancing characteristics in the vaccine.

According to the WSJ, some researchers point to the ongoing Phase III trials as a crucial marker in proving that these vaccines will not raise the risk of disease enhancement.

Will the Treatment Include One Shot or Two Shots?

Bloomberg reports that, according to an immunologist at the Duke Human Vaccine Institute, almost all standard vaccines are multiple-shot regimens.

Of course, standard vaccines typically aren’t compressed into a one year development and manufacturing process in the midst of a global pandemic.

Given this environment, Bloomberg notes that there are mixed sentiments relating to what the more effective and practical approach for administering the vaccine will be. While the article notes that some of the most promising results from early trials are the result of a two shot approach, the logistics involved in distributing a two shot vaccine around the world could be a massive undertaking.

Vaccinating the Older Population May Pose Some Complications

While there is still much we do not know about COVID-19, one clear development is that the elderly are especially vulnerable to the disease’s worst effects. After all, an analysis of over 50,000 deaths conducted by the CDC found that 80% of the fatalities were among people 65 or older.

Protecting this demographic from being sickened with COVID-19 will be a crucial part of re-opening society in a safe and effective way. However, vaccinating older populations corresponds with different complications and difficulties.

National Geographic reports that a key roadblock derives from the thymus, the gland that is the source of T-cells. T-cells are being targeted as a crucial component of a COVID-19 vaccine, as some studies are reportedly indicating that T-cells may be the key to providing any form of lasting immunity against SARS-CoV-2, the virus that causes COVID-19. These T-cells, per the article, help pass along instructions that vaccines provide for our immune systems.

However, according to National Geographic, “aging depletes the arsenal of adaptable T-cells because the thymus fills up with fatty tissue.”

National Geographic notes that the dysfunction of the aging immune system, a concept known as “immunosenescence”, is something that vaccine makers have been contending with for years. Some vaccine companies have displayed levels of success in stimulating vaccines to compensate. For example, in 2014, one large vaccine enterprise developed an influenza vaccine targeting those 65 or older that triggered the body to make more antibodies by infusing four times as much of an immune stimulating ‘antigen’ as a normal vaccine. The result? The vaccine was 24% more effective on this demographic than a typical dose. However, the article does note that these tactics, which are essentially booster shots on more conventional vaccines, may be tougher to replicate for COVID-19, since this disease has never been encountered before.

In addition to immunosenescence, National Geographic points to another challenge scientists face when vaccinating elderly people: “inflammaging.” Per the article, this is when “[elderly people’s] immune system is preoccupied with fighting viruses that cause lifelong infections once they enter the body, such as the typically benign cytomegalovirus (CMV)…the immune system is essentially stuck in an inflammatory state…. That might make it harder for the body to detect a new pathogen like COVID-19—or to get stimulated by a vaccine against it.”

Lastly, National Geographic points out another dynamic that might have uncertain impacts for elderly people:

because of exposure to a lifetime of cold-causing coronaviruses, seniors may already have a repertoire of antibodies that glom onto SARS-CoV-2, the virus that causes COVID-19. That could counterintuitively hamper the body from designing better antibodies against it.

Or, past infections by such germs could be a good thing. There’s new evidence that exposure to the 2003 SARS outbreak or coronaviruses from animals has equipped some people with a T-cell response against SARS-CoV-2. Broader study is required to determine the extent of this protection and what it might mean for a vaccine, given the virus may still be completely novel to many immune systems.

What Proportion of People Will be Willing to Vaccinate?

Not too long ago, concerns with vaccine manufacturing pertained to the supply side: What groups will get vaccinated first? How long will it take for the world to receive their vaccine?

But it appears this sentiment may be shifting to the demand side. Will people be willing to be an “early adopter” of this brand new vaccine? Will enough people be vaccinated for us to achieve herd immunity?

The New York Times has reported on a couple of polls that may reflect a level of distrust in the vaccines that will ultimately be released. For example, a poll in May conducted by The Associated Press-NORC Center for Public Affairs Research found that only around 50% of Americans claimed that they would be willing to get a coronavirus vaccine.

If this ends up being the rate of people that get vaccinated, then this may limit our ability to achieve herd immunity, which, per the Mayo Clinic, “occurs when a large portion of a community (the herd) becomes immune to a disease, making the spread of disease from person to person unlikely. As a result, the whole community becomes protected – not just those who are immune.”

The Mayo Clinic states that the threshold of people that need to be immune in order to achieve immunity varies by how contagious a disease is. For example, measles, which is highly contagious, requires that 94% of the population be immune to enable herd immunity.

In addition to herd immunity, some experts also believe that this may represent a crossover point in public trust—or lack thereof—in the public health community. The Times pulled an excerpt from a report released by a nationwide task force of 23 epidemiologists and vaccine behavior specialists, which stated, in part, that:

If poorly designed and executed, a Covid-19 vaccination campaign in the U.S. could undermine the increasingly tenuous belief in vaccines and the public health authorities that recommend them — especially among people most at risk of Covid-19 impacts.

We have previously posted on the anti-vax movement and the complications it had already presented, even pre-COVID-19. If there are issues with the administering of the vaccine—even if they are heavily isolated—then the level of distrust in vaccines could continue to grow in the years to come.