We have all heard the long-awaited news that the FDA has approved the Pzifer/ BioNTech’s COVID19 vaccine - BNT162b2 for emergency use. I am sure that everyone has a list of burning questions about the vaccine so I took the liberty to read through relevant reports on the phase 2/3 clinical studies and as accurately as I can, summarize and simplify the key results.
What type of vaccine is BNT162b2?
BNT162b2 is a mRNA vaccine that contains modified mRNA encoding for the SARS-CoV-2 spike glycoprotein (S protein) encapsulated in nanolipid particles. When introduced into our body, cells will use the mRNA to produce the S protein. This will allow our immune system to recognize this foreign viral S protein and produce antibodies against it.
Pfizer has two vaccine candidates, which one is THE one?
The two mRNA-based vaccine candidates Pfizer has are BNT162b1 and BNT162b2. BNT162b1 contains mRNA encoding for the secreted trimerized SARS-CoV-2 receptor–binding domain while BNT162b2 contains full-length mRNA encoding for the virus S protein. Walsh et al., 2020 conducted a small trial involving 195 participants and determined that BNT162b2 was a better candidate (1).
Isn’t the vaccines against the coronavirus just like a flu shot we take annually?
No. It is crucial to understand that before the COVID19 pandemic, there has been no vaccines against coronaviruses. Flu viruses belong to a completely different family of viruses called influenza viruses. The flu vaccines you are familiar with are typically live-attenuated vaccines or inactivated vaccines while the BNT162b2 vaccine is a mRNA vaccine. The concept of mRNA-based vaccines is relatively novel and have not been widely used and tested.
How is the vaccine delivered?
The vaccine is delivered intramuscularly, just like the flu vaccine, but the proposed regimen is two doses, 21 days apart.
Will everyone be getting the COVID19 vaccine?
No. The vaccine is only meant for individuals 16 years of age and older. Pregnant and breastfeeding women, immunocompromised individuals, individuals on immunosuppressants need to consult their doctors to discuss risks and benefits.
What does the results from the ongoing study tells us?
According to the Phase 2/3 clinical trial involving 44, 000 participants reported by Polack et al., 2020 (2) the vaccine is able to provide 95% protection against symptomatic COVID19.
Has the Phase 3 clinical trial ended?
No, the study is conducted in the US, Argentina, Brazil, Germany, South Africa and Turkey and is still ongoing. FDA mandates that the data from the Phase 3 study should include a median follow-up duration of at least two months after the completion of the full vaccination regimen (both doses). Only when every participant has completed their follow-up, will the study conclude. The rationale is that the two-month follow-up period allows for identification of potential adverse events that may happen due to immune reactions.
So…is it safe?
‘Safety’ is determined by reactogenicity assessments that includes local reactions at sites of injection (pain, redness, swelling) and systemic reactions such as fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain. According to Polack et al., more vaccine recipients reported mild-to-moderate pain at injection site within 7 days than placebo recipients and less than 1% of participants reported severe pain.
Systemic reactions were reported more often after the second dose, with fatigue and headache being the most common systemic events (59% and 52% respectively). Severe systemic reactions were reported in less than 2% of the vaccine recipients.
Few participants in either vaccinated or placebo group reported severe adverse events.
In summary, based on the report, the vaccine is safe by way of local and systemic reactions. Pain at site of injection is common and fatigue, headache and even fevers may occur post-injection. There is a small chance of developing severe adverse reaction to the vaccine.
In Polack et al.’s report, there were vaccine recipients that died, is that true? Should I be concerned?
Yes, it is true that there were two vaccine recipients died but of non-COVID19 and non-vaccine related causes; most likely due to pre-existing underlying health conditions. There is no reason to be concerned.
Can I get COVID19 from the vaccine?
No. Unlike flu vaccines, the COVID19 vaccines (including BNT162b2) do not use live or even whole viral particles, therefore there is no way of acquiring the illness from the vaccine.
Will I still get COVID19 after I am vaccinated?
It might be possible although it is unclear as to how and why that is the case. According to Polack et al.’s report, one vaccine recipient had a severe case of COVID19 and eight had symptomatic COVID19 after vaccination (even though all nine recipients completed both doses of vaccination). More studies have to be done.
Some important caveats
1. It is always a good idea to look at the demographics of the participants when it comes to clinical trials:
- Gender proportion is almost half-half (which is good).
- Racial profile is 81.9% White, 9.8% African American, 4.4% Asian participants, 26.2% of participants were Hispanic/Latino. It is important to note the small % of minority races.
- In terms of age, 21.4% of participants were >65 years of age and the media age was 51 years.
2. Sample size of Polack et al.’s study was 44,000. Given that the vaccine is ultimately meant to be used globally, a sample size <50 000 could arguably be considered small. In the report, Polack et al. acknowledged that the limited sample size is not large enough (in addition to the short two-month follow up period) to reliably detect less common adverse effects, if any.
3. Safety and efficacy beyond two months were not included.
4. Safety and efficacy in special groups of people like children, pregnant women and immuno-compromised persons were not included. Studies pertaining to these groups of individuals are just starting/ still ongoing.
5. Repercussions of missing the second vaccine dose is unknown.
Some concluding statements
There are many confounding variables pertaining to the study – lock-down measures and infection rate in a country, lifestyles and movements of individuals etc that may skew the results of the study. Think about it this way, what if a vaccinated-individual stays at home most time of the day, practices all the strict social-distancing precautions and has minimal movements, there is very low chance of the individual getting infected in the first place. So, it is difficult to determine if the vaccine is actually protecting said individual.
The most direct way to know if the vaccine is effective to protect one against SARS-CoV-2 is to take a vaccinated-individual and place them in the same room as a COVID19 patient and then observe if the vaccinated-individual will develop the illness. But obviously, such a method is unethical. Therefore, the best group of individuals to ‘test’ the efficacy of the vaccine is frontline healthcare workers whom are exposed to COVID19 patients daily. Results from studies that incorporate frontline healthcare workers will surely be more convincing to show efficacy of the vaccine.
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