BioNTech/Pfizer vaccine has been approved. What do we know about it?

In the end of December, Italy and all the other European countries have started the covid-19 vaccination campaign, thanks to the approval of the BNT162b2 mRNA vaccine developed by BioNTech/Pfizer.

What do we know about efficacy and safety of the vaccine? Results of the clinical studies have been published in mid-December in the New England Journal of Medicine.

BNT162b2 is a lipid nanoparticle-based vaccine; this means that it is constituted by an RNA molecule encoding the SARS-CoV2 protein Spike –which is the protein expressed on the viral surface and required to mediate infection– embedded into a lipid particle. Spike proteins exist in two different forms: the so-called “pre-fusion conformation” before the virus enters and infects mammalian cells, which undergoes major rearrangements, adopting  a different form, upon infection, when the virus fuses with the mammalian cell membrane. The RNA sequence of BNT162b2 vaccine has been slightly modified compared to the original sequence of the virus and it has two mutations that prevent the rearrangements occurring during infection: the protein produced starting from the RNA molecule of the vaccine thus remains in the pre-fusion form.

 

Main results. Safety and efficacy in preventing covid-19 disease of two doses of the BNT162b2 vaccine administered 21 days apart have been evaluated, showing 95% efficacy and a favourable safety profile. With these results, the vaccine has been approved through an emergency use authorization.

 

Experimental details. Previous results had shown that 30 microgram-dose of the vaccine elicited the production of neutralizing antibodies and specific response of the immune system (mediated by CD8 and CD4 T cell subtypes). Antibody concentration in vaccinated people was higher than that observed in convalescent patients, though overall lower in adults and higher in youngers.

Based on such promising results, the vaccine entered a successive phase to further assess safety and efficacy of two 30microgram-doses administered via an intramuscular injection, 21 days apart, compared to people injected with a saline solution (the placebo group). The trial was conducted between July 2020 and November 2020 and included 43.448 healthy (or people with stable chronic medical conditions, such as HIV, hepatitis B and C virus infection) white, black, hispanic people (respectively 83%, 9%, 28%), of both genders (49% females), in US, Argentina, Brazil, South Africa, Germany, Turkey. The trial included also obese people. Median age of the participants was 52 years old. Of the total 43.448 subjects enrolled in the study, 21.720 were randomly assigned to receive the vaccine, while 21.728 received the placebo (the saline solution).

Safety. Subjects were observed for 30 minutes after injection for any acute reactions. Reactions occurring soon after vaccination (which are physical manifestation of the inflammatory response to vaccination) included: 1) local reactions, such as mild/moderate pain at the injection site within 7 days from injection (only 1% reported severe pain), more rarely redness or swelling, and resolved within 1 or 2 days; 2) systemic reactions which were more commonly observed in younger people (under 55 years old), and more often after administration of the second dose rather than after the first dose. More frequent systemic reactions included fatigue and headache (however, these were reported also by some participants in the placebo group). Less than 2% of the vaccinated people reported more “severe” reactions (for instance, fever measured after vaccine administration is classified as mild if in the 38-38.4°C range, moderate if in the 38.4-38.9°C range, severe if in the 38.9-40°C range, fourth grade if over 40°C). In particular, fever between 38.9-40°C was observed in 0.2% of the vaccinated people (0.1% in the placebo group) after the first dose and 0.8% after the second dose (overall fever was more frequently reported in younger adults). Two participants only had fever over 40°C. Reactions were observed 1 or 2 days after vaccination and resolved shortly after; 3) Adverse events: adverse events were observed more frequently in vaccinated subjects than in the placebo group. 0.3% of those receiving the vaccine reported changes in size and consistency of lymph nodes. Four more serious adverse events were reported in people who received the BNT162b2 vaccine, such as shoulder injury related to vaccine administration, alteration of heart frequency, abnormal sensation of the skin of the leg, changes in size and consistency of lymph nodes in the armpit (the latter one, which generally resolved within 10 days, is likely to be the result of a robust vaccine-elicited immune response).

Overall, safety profile of the BNT162b2 vaccine appeared similar to that of other vaccines.

Monitoring will continue for two years after administration of the second dose of the vaccine to gather further information about safety.

Efficacy. The BNT162b2 vaccine showed to be 95% effective in protecting against covid-19 disease, meaning that only 8 people showed covid-19 disease symptoms 7 days after being administered the second dose of the vaccine, compared to 162 people manifesting covid-19 disease among those who received placebo. Between the first and second dose, the vaccine was 52% effective; in particular, partial protection started to be observed 12 days after the first dose administration. One person had severe covid-19 disease after receiving only the first dose of the vaccine, further indicating the importance of the 2-dose administration of the vaccine.

Currently the vaccine needs to be stored and shipped at very cold temperatures but can be kept in common refrigerators for up to five days. 

 

Conclusions. BNT162b2 mRNA vaccine showed a favourable safety profile and 95% efficacy against covid-19. Furthermore, studies proved that covid-19 can be prevented by immunization, showed that RNA-based vaccines are highly promising tools against infection diseases and epidemics, which can be produced in reasonable times (the development of the BNT162b2 vaccine started in January 2020) simply requiring knowledge of the viral genetic sequence.

The number of people included in the study represent a group size large enough to have 83% probability of detecting at least one adverse event, even though is not sufficient to detect possible less common adverse events. Due to the short follow up (two months), there is no information available yet about the duration of protection from covid-19 elicited by the vaccine or about potential adverse events that might occur over two months after the second dose. Finally, so far there are no data available to determine whether the vaccination is effective in preventing asymptomatic infections and whether is effective in preventing covid-19 infection in pregnant women, people younger than 16 years old and immunocompromised people.

 

 

 

Reference. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. Fernando P. Polack et al., The New England Journal of Medicine 2020.