The BNT162b2 mRNA Covid-19 vaccine, popularly known as the
Pfizer vaccine is the first Covid-19 vaccine to receive authorization for use
in the general public. The first jab was given to a 90-year old lady in the UK on December 8, 2020; a monumental event that brought hope to billions of people all across
the globe. In this article, I will discuss this vaccine’s clinical trial and potential
future implications.
How does it act?
The BNT162B2 is a lipid nanoparticle-formulated,
nucleoside-modified mRNA that encodes the SARS-CoV-2 full-length spike protein,
modified by two proline mutations to lock it in the prefusion conformation. This
means that this is an mRNA that has been modified to resist disintegration by
nucleases and that translates into the SARS-CoV-2 spike protein. However, this
spike protein has also been modified to lock it into its pre-fusion
conformation; so that it doesn’t fuse with the target cell’s plasma membrane and
remain exposed to immunogenic stimulation.
Who is it for?
This primarily depends on the characteristics of the population
included in the vaccine’s clinical trial. This trial randomised 43,458 persons
from six countries: USA, Argentina, Brazil, South Africa, Germany, and Turkey. More
than three-fourth of the study population (76.7%) belonged to the USA. Moving
on to the representation of race or ethnicity in the study population - 82.9% were
white, 27.9% were Hispanic, while African Americans, Asians, and Native
Americans comprised 9.2%, 4.2%, and 0.5% of the study group. Males and females
were almost equally included. The age range is from 16 years to 89 years in the
intervention group. This trial did not evaluate the efficacy of the vaccine in
children, adolescents, and pregnant women.
Is it effective?
Define effective; it depends on the trial’s efficacy end
points. The primary endpoint was the efficacy of the vaccine to prevent Covid-19
infection 7 days after the second dose in participants who had no serologic
(antigen and antibodies) or virologic (RT-PCR) evidence of SARS-CoV-2 infection
up to 7 days after the second dose; the second primary endpoint was to prevent
infection in those with and without evidence of prior infection. Confirmed
Covid-19 was defined as – the presence of at least one symptom (fever, new or
worsened cough, new or worsened dyspnoea, chills, new or worsened muscle pain,
new loss of taste or smell, sore throat, diarrhoea or vomiting combined with a positive
RT-PCR test within 4 days).
|
Efficacy End Point
|
BNT162b2 Group
|
Placebo Group
|
Vaccine efficacy, % (95% credible interval)
|
|
Covid-19 Cases
|
N
|
Covid-19 Cases
|
N
|
|
1st Primary
|
8
|
18,198
|
162
|
18,325
|
95(90.3-97.6)
|
|
2nd Primary
|
9
|
19,965
|
169
|
20,172
|
94.6(89.9-97.3
|
This trial showed that a two-dose regimen of BNT162b2 (30 micrograms per dose, given 21 days apart) was 95% effective in preventing symptomatic
Covid-19 infection 7 days after its course. The efficacy was 52% after the first
dose, and 91% in the first 7 days after the second dose.
However, the trial results did not show the efficacy in
preventing asymptomatic infection. We don’t know if this vaccine can safeguard
against transmissible asymptomatic infection; therefore, people who have taken
the vaccine should not stop wearing masks for the sake of the people around
them.
Is it safe?
The vaccine group reported more local reactions, such as
pain, redness, and swelling at the injection site than the placebo group. In
general, these were mild-to-moderate in severity and resolved within 1-2 days.
The systemic adverse effects were also reported more in the intervention group,
especially in the younger population (16 to 55 years of age), and more after
the second dose. These included – fever (11%), fatigue (51%), headache (39%),
chills (23%), muscle pain (29%), joint pain (19%), and 38% of the vaccine group
needed to use antipyretic medication. These were generally mild and resolved
within 1-2 days. Two deaths happened in the vaccine group, one from
arteriosclerosis, and one from cardiac arrest. These deaths weren’t related to
the vaccine or Covid-19. The investigators plan to continue the surveillance
for adverse events for further 2 years.
This study has importance beyond the efficacy of the
BNT162b2 vaccine candidate. It demonstrates the utility of RNA-based vaccines, its
speed of development, and its promising efficacy in preventing infectious
diseases. The success of this clinical trial immensely improves our preparedness
for a future pandemic.
Reference:
Polack, FP, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. New England Journal of Medicine. Dec 10, 2020. 10.1056/NEJMoa2034577. C4591001 Clinical Trial group
-Vinayak
