COVID-19 Update: Is the Pfizer vaccine getting approval in October?

Pfizer claims that it has so far recruited about 23,000 of the projected 20,000 participants.

Preamble
This new pandemic called Covid-19 has ravaged nearly all countries of the world and yet this alarming global scourge is still not showing any signs of slowing down. As of this writing, there are about 26.8 million cases of infection globally, with nearly 8.8 lakh deaths. India is the third worst affected country, with over 40 lakh (4 million) cases of infection, and nearly 70,000 deaths.

Manipur's situation is not yet alarming but there is also no room for complacency. The government is taking all possible steps, I believe, to contain the disease. However, if the public doesn't strictly abide by the recommended control and preventive measures such as use of masks, social distancing, hand hygiene, regular use of soaps and hand sanitizers and religious maintenance of quarantine/isolation SOPs, the outbreak may go out of control! Till date, the number of cases in Manipur have shot up to 6,699 cases with 4,899 recoveries and the number of deaths currently at 36.

In this column, I would like to review the status of the vaccine made by the US pharmaceutical giant, Pfizer Inc. in coordination with the German firm, BioNTech and the likelihood of its getting FDA approval by October-end 2020.

What is Pfizer Vaccine?

The Pfizer vaccine is based on BioNTech's mRNA-based vaccine platform. It joined the global vaccine race as early as mid-January when the genetic sequence of SARS-CoV-2 (the coronavirus causing Covid-19 pandemic) was made public by Chinese scientist. Pfizer/BioNTech initially began with 4 vaccine candidates. Two of these 4 candidates:-BNT162b1 and BNT162b2-subsequently progressed to human clinical trials in US and Germany.

Pfizer joined the race as a late-bloomer, a bit later than Moderna, another US firm who is also developing a Covid-19 vaccine based on the mRNA vaccine platform. Though Moderna's Phase 1 trial began on March 16, Pfizer's Phase 1/2 trial began only
in April. On April 23, 2020 12 volunteers (18-55 years of age) in Germany were Random Musings-32 injected with either of the two vaccine candidates whereas participants in US (18-55 years of age) were given shots of either vaccine on May 5.

Based on safety data from early-stage trials including preclinical and clinical data, BNT162b2 was chosen for advancing into Phase 2/3 (large-scale, late-stage) trials which started in US on July 27, 2020. About 30,000 volunteers in the age group 18-85 are expected to participate globally (except China) spread in 120 locations. Pfizer claims that it has so far recruited about 23,000 of the projected 20,000 participants.

What is BNT162b2?

It is a modified messenger RNA (modRNA) vaccine candidate. It mimics part of the genetic instructions of the SARS-CoV-2 virus (instructions for making the virus particle inside an appropriate host cell), that represents the spike protein that sticks out of the surface of the virus giving it the characteristic crown-like (corona) appearance.

The spike protein is the key that unlocks the ACE2 receptor on human cell surfaces to enable the SARS-CoV-2 coronavirus to enter human cells; a critical part that may be targeted by the immune system to prevent the virus from entry and/or making copies of itself (replicating); thus stopping further transmission of the virus ultimately.

The modRNA molecule is enclosed by a lipid membrane to protect the RNA (in the final form of a lipid nanoparticle) from degradation. Once it is delivered inside the human body, it hijacks the host cell machinery in particular the ribosomes (the protein-making factories), so that instructions in the RNA molecules are read and translated into the spike proteins. The spike protein then educates (stimulates) the body's immune system (our defense army) to generate anti-SARS-CoV-2 antibodies and, possibly, activated T cells (special protective cells of the immune system). Once the immune system in a vaccinated individual is activated, it would remember the identity of the virus if that person is subsequently exposed to the virus and the immune response elicited would protect the individual from getting infected (the vaccine might also reduce the severity of Covid-19 in an already infected person). It is a bit like catching a criminal by recognizing unique lumps on his head.

The BNT162b2 vaccine acts as a kind of missile to deliver the RNA inside the human body and then generate a proper immune response against SARS-CoV-2. However, a successful vaccine while being effective (preventing the infection), must also be safe (not causing dangerous adverse effects). That is why a candidate has to undergo a prolonged trial spread into 3 phases (with phase 3 being the most crucial stage).

Why was BNT162b2 Selected for Late-stage Trials?

The phase 1/2 data of the BioNTech vaccine has now been published in the prestigious British journal, Nature (August 12, 2020; doi:10.1038/s41586-020-2639-4). The vaccine was administered in 2 doses of 30 micrograms each, 21 days apart. The findings indicate that, 7 days after the second dose, there was significant neutralizing antibody titer, geometric mean titer (GMT) in the blood of vaccinated individuals
that was about 2.8 times the GMT in convalescent plasma of people who recovered from SARS-CoV-2 infections. The antibody titer was significantly less in elderly patients. Data of about 120 participants receiving either BNT162b1 oe BNT162b2 were analyzed and reported in this article.

The side effects were also found to be generally mild to moderate and transient (1-2 days) events such as injection site pain, fever, chills, fatigue and no other adverse effects. The vaccine candidate (BNT162b2) was associated with less adverse side-effects compared to BNT162b1 especially in elderly individuals.

Preliminary results of phase 2/3 trials of BNT162b2 have been published and the vaccine scientific teams claims that the data are quite promising (medRxiv, preprint, August 28, 2020; doi:10.1101/2020.08.17.201/20176651). The phase 3 trials are, however, still incomplete. The final, analyzed phase 3 data and peer-reviewed publications based on them are still awaited, with a bated breath! The non-peer-reviewed paper claims that the vaccine elicited significant dose-dependent neutralizing antibody GMTs in both younger and older persons.

Phase 3 trials of the Pfizer vaccine is still ongoing and the world can only hope that, ultimately, a successful vaccine comes out which is efficacious (protects at least 50% of vaccinated people from SARS-CoV-2 infections), safe (no long-term, serious adverse events), affordable (not very costly), and equitable (that is, easily accessible to poor countries besides the developed nations).

Is the Pfizer Vaccine Getting Approval in October, 2020?

Recently, there have been quite a few reports indicating that the Pfizer/BioNTech vaccine is likely to get US FDA approval latest by October-end, ahead of the Moderna vaccine. One can only hope that as and when the approval is granted it i s based on scientific and medical considerations instead of political considerations. There are also rumors that President Trump is exerting immense pressure to release a vaccine ahead of the November 3, 2020 US Presidential elections.

Some drawbacks of the BNT162b2 vaccine include: non-completion of phase 3 results especially of efficacy (at least, 50% protection), safety (no serious side-effects), non-publication of peer-reviewed articles detailing phase 3 data, non-inclusion of people with co-morbidities, non-inclusion of young people (less than 18 years) and less representation of Hispanic, Black, and Asians in the trials (the majority of the
volunteers seem to be white American males). Let's remember that, as and when this or any other vaccine(s) becomes available, it has to be produced in adequate amounts (several billion doses), distributed, and administered across the globe. If any region of the world remains vulnerable to Covid-19, our planet would still be threatened with this wily coronavirus.

Vaccine nationalism versus vaccine equity

Many rich countries have pre-ordered several million doses of the candidate vaccines in late-stage trials. USA is said to have pre-purchased at least 4 candidate vaccines for its citizens. So, as and when 1 or more vaccines pass the test and becomes available, would they be equitably distributed around the world or would the successful vaccines be monopolized by just a few rich nations? Most reports indicate that even if a successful vaccine gets approved by the end of 2020, large-scale production, supply-chain creation, distribution, and administration
globally would be possible only by the end of 2021.

As far as developing and populous countries are concerned, the more the vaccines, the merrier it will be. There are several benefits from a multiplicity of vaccines. One, by the law of simple supply-and-demand, the more the vaccines the lower would be the cost. Two, more vaccines would likely yield better, more effective and safer vaccines, especially those which come after the initially approved ones. Three, people would get more options: one vaccine may be more suitable for some individuals and others more convenient for other groups of individuals.
Let's all hope that the last-stage trials of all the frontrunners including Oxford/AstraZeneca, Moderna/NIH, Pfizer/BioNTech, Sinovac, Sinopharm, Gamaleya and other candidates pass the crucial trial and come to the market quickly and save the world from further ravages by the Covid-19 pandemic.

Coda

There is as yet no approved cure or vaccine for COVID-19. Meanwhile, it's likely that the number of morbidities and mortalities would continue to soar across most parts of the world including India (and Manipur). What then should we do meanwhile before the development of an approved cure or vaccine.

The government must strictly enforce the standard SOPs for tracing, testing, and treating potential infection cases. Within the limits of the available budget, testing must be scaled up to catch more of potential infections including asymptomatic cases.If  feasible, antibody based screening (serosurveillance) may be done in infection hotspots to monitor the spread of the infection and percentage of population who has
developed immunity against the Covid-19 virus. Three kinds of hospitals or treatment facilities need to be set up: first, to treat critical Covid patients; second, to address non-Covid cases, and third, to manage long Covid recovered individuals.

The general public must also religiously abide by the necessary control and prevention measures (use of masks, social distancing, hand hygiene etc.); we need to be a tad altruistic: please remember that you're sacrificing a little bit of your creature comforts not just to save your own life but also others' lives!

First Published:Sept. 6, 2020, 12:23 p.m.