The Infectious Disease Specialists at Crystal Run Healthcare have been following the Coronavirus pandemic and the development of COVID-19 vaccines closely. Here’s what Board Certified Infectious Disease Specialist, Oladipo A. Alao, MD, MPH, FACP, wants patients to know about COVID-19 vaccines, from development and timelines to the different types and possible side effects.
COVID-19 Vaccines – What We Know
In December 2019, the first cases of what would become known to the world as Coronavirus or COVID-19 emerged in Wuhan, China. The virus shared similarities with ‘SARS’, a respiratory illness that spread in China from 2002 to 2004. Before scientists knew how bad the outbreak of ‘SARS’ would be, they began to develop vaccines and test them in Phase 1 trials. When the outbreak no longer seemed like a threat, the development of vaccines stalled. But what was done over a decade ago was not done in vain. This work provided the platform for an accelerated timeline for the development of COVID-19 vaccines, reducing the time needed to be spent on exploratory vaccine work and design.
Vaccine Development
To develop a vaccine, one must understand how the virus is attacking cells. Both coronaviruses, ‘SARS’ and COVID-19 use the spike protein to attach to cells. The spike protein facilitates receptor binding to the angiotensin-converting enzyme2, which is an enzyme that controls blood pressure, on the host cell, and membrane fusion. Researches have targeted the spike protein and its receptor binding domain for the development of vaccines. Vaccines that produce antibodies to the spike protein targets have been shown to neutralize Coronavirus and form protection first in non-human primates and then in humans.
We’ve heard a lot of talk about the development timeline. Yes, it’s easy to hear “Operation Warp Speed” and wonder about the process, but while the vaccine was developed faster than usual; an accelerated vaccine timeline does not mean that any phases of clinical trials were skipped. Companies carefully planned the development to save time if things went well and since the prior research and initial results showed promise, companies were able to overlap steps:
- Phase III clinical trials started after initial analysis of Phase I/Phase II trials;
- Commercial production started before final results from Phase III trials;
- Reviews were expedited;
- Vaccines were approved through Emergency Use Authorization (EUA).
Companies were able to overlap these steps because the initial information from each was so promising. They ensured all of the proper steps were taken, just in less time!
What are the types of COVID-19 vaccines?
Researchers have used many methods to develop COVID-19 vaccines. They’ve utilized traditional vaccine pathways, such as the use of live attenuated virus vaccines, inactivated virus vaccines, and more recently developed pathways such as recombinant protein vaccines, replication incompetent vector vaccines, and replication competent vector vaccines, inactivated virus vector vaccines, DNA and RNA (ribonucleic acid) vaccines.
RNA vaccines have been developed relatively recently and can either be mRNA or self-replicating RNA. The mRNA delivers the antigen’s genetic information so the cells in the body can make that antigen. To combat COVID-19, mRNA are delivered by the lipid nanoparticles (LNP) to ensure they get to their destination. The mRNA are degraded shortly afterwards and have no effect on the person’s DNA. The antigen made by the cells then generates an immune response to neutralize the virus.
The advantage of RNA vaccines is that the process does not involve working with the actual virus; however, RNA vaccine technology is still being improved. Large scale production and storage of these RNA vaccines pose unique challenges for distribution.
The first two COVID-19 vaccines approved in the U.S.; the Pfizer BNT162b2 and Moderna mRNA-1273, are both mRNA vaccines that went through studies in non-human primates and all 3 clinical trial phases in humans before being issued Emergency Use Authorization by the FDA. Participants were monitored for at least 60 days after the second dose was administered to ensure adequate time to observe if any adverse effects take place. Historically, effects to vaccines tend to occur within that 60 day timeframe. The timeline for these vaccines was accelerated, but not abbreviated, which should lessen the hesitation for safety concerns.
What are the side effects?
The Phase 1 study of the Moderna vaccine started in March 2020 and enrolled 45 participants with 15 each receiving 3 different doses; the interim analysis after day 57 has been published. The Phase 1 trial of both Pfizer BNT162b1 and BNT 162b2 enrolled 195 participants with 13 groups, each group included 12 individuals who received different doses of each vaccine by age categories 18-55 years and 65 years and older. The most common adverse effect for both vaccines was pain at the injection site. To see a more detailed report on side effects or learn more about the vaccines, visit the CDC website: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/expect
The 100µg of the Moderna vaccine was tested in a Phase III trial in July of 2020, enrolling 30,420 individuals 18 years of age or older, who received either the vaccine or placebo. Results 60 days after the second dose was administered were published and showed vaccine efficacy of 94.1 %.Data showed that 196 enrollees, 185 who received the placebo and 11 who received the vaccine, developed COVID-19. The 30µg of The Pfizer BNT162b2 then underwent a Phase III trial involving 43,448 individuals, where 170 developed COVID-19, with only 8 of those recipients in the vaccine group. The results for Phase III trials were recently published and pain at the injection site was again the most common side effect. Since these vaccines became available, there have been about 30 reported incidents of severe allergic reaction to the Pfizer and the Moderna vaccines (last updated January 15th). These occurrences remain relatively rare given that over 27 million doses have already been administered. Vaccine distribution sites have measures in place to observe individuals after doses are administered. While long-term safety data of these vaccines are not yet known, vaccine recipients are being monitored and more information will continue to be gathered.
There are other vaccines being developed using the various vaccine processes highlighted above which should soon be available. COVID-19 Vaccines so far appear to be very effective and are likely to remain effective even against new strains of the virus reported, however, they may not induce ‘sterilizing’ immunity which means vaccine recipients can possibly still get and transmit COVID-19 even if this is highly unlikely. This is why social distancing measures and mask wearing will still be needed to curb the spread of the virus.
Help Fight COVID-19, Get Vaccinated
We need all the help we can get to fight this pandemic because there’s still a lot of the virus circulating in our communities and around the world. Getting vaccinated is another preventive measure that can help protect you from COVID-19; paired with mask wearing, social distancing, and avoiding crowds, you can significantly reduce your risk of catching the virus and becoming seriously ill. At Crystal Run Healthcare, we recommend getting vaccinated to help stop the spread of COVID-19; if you have questions regarding the vaccine discuss them with your provider. Together, we can bring this pandemic to an end.
Oladipo A. Alao MD, MPH, FACP, is a Fellowship-trained Infectious Disease specialist and earned his Medical Degree from College of Medicine University of Ibadan in Ibadan, Nigeria. He completed his Residency in Internal Medicine and Fellowship-training at Harlem Hospital Center in New York, NY. Dr. Alao is Board Certified in Infectious Disease and Internal Medicine and has clinical interests in HIV and travel medicine. He is providing care to patients in West Nyack and Monroe.