For many returning to work or returning to school, this fall is an exciting step toward normalcy. However, even with hybrid plans and adherence to mask-wearing, normality is not around the corner.
It is clear that a vaccine is a critical step in mitigating the public health risk of COVID-19 and returning to our pre-pandemic lives. In light of this, it is helpful and important to understand how new technologies might not only be paving the way for a successful COVID-19 vaccine, but also for a more adaptable vaccine development platform. Furthermore, understanding characteristics of other viruses and vaccines may help us predict some of the characteristics of a future COVID-19 vaccine.
COVID-19 vaccine research is moving at pandemic speed using both traditional approaches and novel vaccine technologies, with five candidates currently in Phase III trials. Phase III is the last stage of clinical development and requires testing the vaccine on thousands of people. After proving safety and efficacy during Phase III trials, a vaccine is able to earn Food and Drug Administration approval.
Two of the Phase III vaccine candidates, the Sinopharm and the Sinovac Biotech vaccines, use the tried and true inactivated vaccine methodology. Inactivated (killed) virus vaccines and their relatives, live attenuated (weakened) virus vaccines, have been very successful in the past with combating viruses such as polio and measles, respectively. Vaccines containing weakened live or killed viruses elicit an immune response by imitating an infection without being infectious. Inactivated vaccines tend to produce a weaker immune response as compared with live attenuated vaccines; however, live vaccines can pose greater risks to the elderly and immunocompromised populations.
While some companies are continuing to use these older vaccine approaches, several new vaccine technologies are demonstrating great potential in the pursuit of a COVID-19 vaccine. The Oxford-AstraZeneca adenovirus vector vaccine is also in Phase III trials. Rather than vaccinating with the whole virus, the adenovirus vector introduces only the harmless SARS-CoV-2 spike protein (protein the immune system recognizes as foreign) and still elicits protective immunity. It does this by using the shell of a modified adenovirus, which is a different non-infectious virus that can target respiratory cells. The modified adenovirus contains the DNA, or genetic blueprint, for both itself and the SARS-CoV-2 spike protein. This allows for the adenovirus to both replicate in the body and for the targeted cells to safely make the spike protein themselves. Presence of the spike protein stimulates the growth of memory immune cells (memory B cells), which can produce antibodies at a later date, providing protective immunity.
Moderna also currently has a vaccine candidate in Phase III that utilizes new messenger RNA (mRNA) vaccine technology. The mRNA vaccines — a subclass of nucleic acid vaccines — are similar to viral vector vaccines in that they also deliver a genetic blueprint to immune cells for the coronavirus spike protein, but they utilize a different delivery system not involving a virus or viral genes. Instead, they use small molecules that can safely enter targeted cells and deliver the spike protein’s mRNA code, which the cells read to make the spike protein. Pfizer/BioNTech also has a vaccine which uses the mRNA approach and is currently in Phase II/III combined trials. Additionally, DNA vaccines are being developed and have a similar mechanism to induce protective immunity.
One of the more exciting aspects of the new vaccine technologies is that they have the potential to be readily adapted for new viral threats, diminishing the time required for vaccine development. If the new approaches are successfully optimized, they could change the way we are able to respond to viruses.
“Currently, we can easily make nucleic acids,” John Parker, PhD, an associate professor of virology at Cornell University, explained. “This means an mRNA vaccine, for example, can be synthesized in a machine, allowing us to develop or modify and produce a vaccine much faster than with older vaccine approaches.”
Not only can the success of these new technologies enable the development of a COVID-19 vaccine, but they could also significantly reduce the amount of time it would take to produce a safe and effective vaccine in the event of future viral threats.
With COVID-19 vaccine development progressing well, it seems the arrival of a vaccine is close. Yet development of an effective vaccine does not mean those vaccinated will have long-term protective immunity. As with some other viral diseases, multiple vaccines may be required. It is still not clear to immunologists why some vaccines produce longer lasting immunity than others, but regardless of the vaccine, if the virus mutates, immune protection can be lost. Therefore, by looking at how other viruses change, it’s possible to predict how often we may need to be re-vaccinated for SARS-CoV-2.
The influenza vaccine is given yearly, but will we need a yearly COVID-19 vaccination, too? Some viruses, such as the measles virus, change very little over time, and therefore do not require updates to the vaccine. Conversely, the influenza virus is known for evolving into new strains frequently. That can be attributed to two main factors. The first factor is a phenomenon known as antigenic drift, which describes the accumulation of mutations in the virus. Once vaccinated during flu season, our immune systems are able to keep up with virus’ small changes. However, during the off-season, the influenza virus continues to mutate in the southern hemisphere. At the start of each new flu season, our immune systems are left vulnerable to the accumulation of mutations, which have produced an unrecognizable influenza virus, a new strain. The second factor for influenza’s high mutation rate involves the influenza’s partitioned genomic materia. It has eight segments. Each virus will sometimes contain less than all eight segments and will “borrow” the missing segments from other viruses that infect the same host. This occurrence is thought to increase the mutation rate. As a result of these two factors, before each flu season the influenza vaccine has to be adjusted to reflect the season’s predicted strains.
So, how often will we need to get a COVID-19 vaccine? According to Mr. Parker, the good news is that currently, the virus does not seem to be changing rapidly. There have only been very minor antigenic variations thus far, experts say. Additionally, the original SARS and MERS, which are very closely related to SARS-CoV-2, have not changed significantly. Therefore, it is likely we will only have to modify the vaccine every few years.
“It is possible we will see antigenic drift in COVID-19 over time, but I wouldn’t expect that it will lead to a new pandemic,” Mr. Parker said. “Rather, it will resort to something that is more endemic,” meaning “it’s around, but most of us have some or partial immunity.”
In sum, the behavior of the virus and its relatives is encouraging for assuring the longevity of vaccine protection. The success of the multiple vaccine technologies thus far is reason for optimism.
It is important to realize, however, that the approval of a vaccine is only a start. We will have to overcome many obstacles, such as distribution of the vaccine and determining who will get it first. That being said, it seems that an approved vaccine is imminent. Until then, preventing the spread of the virus through mask-wearing and social distancing is vital to public health and safety.
Simon Peck is a junior at Cornell University and a Pound Ridge resident.