Beginning of the end!

It’s been more than a year now, that we came to know about the SARS CoV2 virus and the COVID19 disease. In the absence of an effective antiviral drug for this pandemic, vaccine is the way out. Several vaccine candidates came out with remarkably high efficiency from the clinical trials in a record time and got emergency authorization in many countries. Even experts were pessimistic about the rapid launch of any efficient vaccine (so far mumps vaccine was the fastest, which took 4 years). Now we are ready for the biggest vaccination program in the history of mankind. Several questions arise as the vaccines roll out. Whether vaccinated ones are free to travel around? Do the naturally infected ones need vaccine? How long does the vaccine protect us? Can the vaccinated transmit the disease if they are infected? Which vaccine should one take? Remember, this is a new disease, and those authorized vaccines are still on trials, and we are learning more about it and only time will answer most of those questions accurately. Here, I will share the current scientific opinions on several of such questions.

Novel platform vaccines

More than 100 vaccine candidates are undergoing different phases of trials, nearly 20 are in clinical phase 3. In 2020, we have seen tremendous development of vaccines from various vaccine platforms, among them 2 novel platforms viz. mRNA and Viral vectors stood out. These technologies are going to revolutionize the vaccine science of course, moreover, hopefully will evolve into the future medicines for many ailments. Reasons for rapid development of COVID19 vaccines is manifold, mainly several years of research on related viruses, R&D in various novel vaccine platforms, enormous funding, multiple multicentered trials and fast-track decisions from regulatory bodies.

What is an mRNA vaccine?

mRNA is messenger RiboNucleicAcid, which is a transient biological molecule that our cell uses to translate the DNA code to the protein molecule. It is an important class of biomolecule that helps in translating the genetic information (DNA) to the active players (proteins), in our cells. COVID19 mRNA-vaccines (by Pfizer and Moderna) are designed to produce the SARS CoV2 viral spike in the host cells at the injection site. Subsequently the spike proteins will trigger our immune system to create antibodies that recognize and neutralize the SARS CoV2, as well as to trigger cell-mediated immune responses. Thus, the vaccine equips our immune system by creating antibodies that neutralize the attacking pathogens and activate the cell mediated immune responses and keep the memory intact so that our body mobilizes these arsenals quickly upon a real attack by that specific pathogen.

Moderna´s (an US based biotech company) and Pfizer/BioNTech´s COVID-19 vaccines, mRNA-1273 and Tozinameran/BNT162b2 respectively, consists of pieces of ´transient´ genetic information of vital spike protein of SARS CoV2 (information in the form of RNA molecules) packed in oil droplets. In theory, these 2 lead runners are the same, except some differences in their formulations and dose regimens. One concern about such a vaccine is whether it integrates in our genome or stay in our cells! These are transient messages to produce the viral spike protein and are not messages that linger around forever (an analogy often helps is these mRNA vaccines are like ´snapchat´ messages).

What is a Viral vector vaccine?

By utilizing leading edge molecular biology techniques, we can modify even the deadly viruses to harmless tools for specific research and medical applications (like vaccines). Such modified viruses (viral vectors) are useful ‘cargo-vans‘ to deliver foreign genes into host cells. One can alter the genetic material of the cargo virus to remove viral proteins essential for its replication and instead, introduce a foreign gene of interest (e.g. spike protein of SARS CoV2). Non-replicative ´gutless´ viral vectors thus produced have the innate ability enter inside the host cells and produce proteins of interest (for e.g. spike protein of SARS CoV2) instead of viral proteins. Our immune system will take care the rest, as mentioned above.

Several such vector based COVID19 vaccines are undergoing clinical trials. The Jenner Institute’s (University of Oxford) Vector based COVID19 vaccine is the most promising one in the limelight. Their vaccine is ´ChAdOx1 nCoV19´ which is the abbreviation of Chimpanzee Adenovirus Oxford1 novel CoronaVirus 2019) also known as Covishield or AZD1222. The vaccine uses another mild virus (a crippled Adenovirus), that cannot replicate in host cells, but to deliver the code for spike protein of SARS CoV2 and subsequently to elicit the immune response. The genetically modified Adenovirus will infect the host cells but cannot replicate itself. Upon infection, it faithfully expresses the cargo it carries (here the spike protein of SARS CoV2). This foreign protein will evoke the defense system and produce the appropriate immune mechanisms in vaccinated host. Giant vaccine manufacturers like Serum Institute of India (world’s largest supplier of vaccines) is involved in the massive production to provide huge world-wide demands of this COVID-19 vaccine.

Emergency use authorization (EUA) approval

UK approved emergency authorization of the Pfizer vaccine first and kick started the biggest vaccine program in human history. Later, the USA approved the Pfizer and Moderna vaccines. Recently, UK granted approval for the country´s indigenous viral vector Oxford/AstraZeneca vaccine for emergency usage. After that, Europe also issued emergency authorizations for Pfizer vaccine and considering applications of other vaccines. UAE approved China´s Sinopharm and India approved Oxford/AstraZeneca and indigenous Covaxin vaccine for emergency use. Soon other countries may approve and start the marathon vaccination program. 

Vaccine efficiency- what do the data tell us?

There are several questions regarding the emergency authorized vaccines. Whether the vaccine will prevent the transmission of disease is a big question. The trial data shows that they are extremely efficient in protecting the vaccinated from getting severe illness- which is great. But whether the vaccines stop them from transmission to the vulnerable is not certain yet. Whether those vaccines work efficiently in diverse ethnic background and various age groups are other questions. Another question is how long the vaccine provided immunity will last. The vaccines are designed to elicit strong immune responses not only by creating neutralizing antibodies against different regions of spike protein (expressed from vaccines), but also through specialized memory cells- hence the defense system is supposed to be in action multiple ways if it encounters the real threat. Here are the gist of the different phase 3 results so far,

Moderna-mRNA-1273

Moderna vaccine aka the mRNA-1273 vaccine is a lipid encapsulated mRNA-based vaccine that encodes the full-length spike protein of SARS CoV2. Regimen consists of 2 intramuscular injections of mRNA-1273 (100 μg per dose) 28 days apart. The mRNA-1273 vaccine showed 94.1% efficacy at preventing COVID19, including severe disease in persons 18 years of age or above. Apart from transient side effects similar to other vaccines, no safety concerns were identified. Out of the 30,420 volunteers, 11 cases of symptomatic COVID19 were observed in vaccine group, while 185 cases were identified in placebo group.

Pfizer/BioNTech

Pfizer/BioNTech vaccine known as BNT162b2 is a lipid droplet enclosing a modified mRNA that codes for SARS CoV2 full-length spike protein. A two-dose regimen of BNT162b2 (30 μg per dose), 21 days apart provide 95% protection against COVID19 in persons 16 years of age or above. Adverse events observed were similar to those associated with other vaccines, such as mild-to-moderate pain at the injection site, fatigue, headache etc. Based on their data, from 43,548 participants- 8 cases of symptomatic COVID19 in vaccine group, while 162 cases were reported in placebo group. Whether this vaccine protects against asymptomatic infections and thereby spreading to unvaccinated vulnerable people is unanswered.

Oxford/AstraZeneca

Oxford/AstraZeneca viral vector vaccine is cheaper and easier with transportation & storage than the two mRNA-based vaccines which need extreme low temperatures. Oxford/AstraZeneca were the first among the vaccine candidates to publish the Phase-3 trial results in a peer-reviewed journal. During their interim results they announced about a ‘dosage error’, i.e. some of the participants received only half the dosage of the first jab (!). The standard plan of two doses of the same strength administered a month apart — had an efficacy of 62%, whereas the regimen with a lower first dose- had an efficacy of 90%. So, the data from different dosing regimens were pooled and they observed that the vaccine was 70% effective at preventing symptomatic infections. Intriguingly, those participants with lower first dose showed increase in efficacy compared to the standard-plan participants. Though the dose calculation error made the data interpretations complicated, it becomes ‘beneficial’ here, while it is difficult to explain the reason behind higher efficiency with current data. All together the interim data looks very promising that the vaccine has acceptable safety profile and is efficacious against symptomatic COVID19. But may need more data or a follow up study to come to a concrete conclusion (due to the dose complications). 

Further, they reported that the efficient low dose plan was 60% effective in reducing the asymptomatic infections, which means though the vaccinated are protected from serious illness and hospitalizations, they are prone to asymptomatic infections and thereby can spread around the virus. Suggesting the necessity of public health measurements for a long time!

Other vaccines in EUA list

Chinese-state owned Sinopharm vaccine (2 doses of inactivated vaccine) got approval in several Arab nations after claiming 86% efficiency. In a press release UAE stated that 99% of those vaccinated developed neutralizing antibodies against SARS CoV2 and that the vaccine prevented the vaccinated from severe disease. Interestingly, Sinopharm recently said that the vaccine is 79.34% effective and obtained approval in China. Similarly, Russia´s Sputnik V, the first registered viral vector vaccine from state-run Gamaleya institute claimed more than 91% effective, based on interim Phase 3 trial results. Along with Oxford/AstraZeneca’s Covishield (Serum Institute India is the production partner), another inactivated vaccine from Bharat Biotech (Covaxin) got restricted emergency authorization in India, though they are still recruiting volunteers for the clinical phase 3. Detailed efficiency data on any of these have n´t appeared in peer-reviewed journals yet. 

Side effects

Reactions like pain at the injection site, fatigue, mild fever, chills, joint aches are quite common and appears as your immune system kicks in upon vaccination. You may remember such unpleasant episodes after your childhood vaccines. If one gets such common mild-to-moderate side effects, it is reflected as vaccine is doing its proper job. The reported serious allergic reactions (less than 1 in 100,000) of emergency approved vaccines are less on comparison with some medications (e.g., approx. 10% are allergic to Penicillin therapy). Usually, the adjuvants in the vaccines can cause some adverse effects. In order to have an enhanced immune reaction and very efficient immunologic memory, vaccines are usually mixed with some adjuvants. An adjuvant is any substance that accelerates, prolongs, or enhances immune responses in combination with specific vaccine. The mRNA vaccines contain a compound called PEG which may be the culprit of some of the rare allergic reactions reported after the vaccination. People at high risk of an anaphylactic reaction should stay at the vaccination center for 30 minutes after their shot so they can be treated in case of any allergic reactions.

Which vaccine should I take?

Provided the vaccine is approved for safety and efficacy, if offered, one should take it. The faster you take the vaccine the better. Even the COVID19 survivors are recommended to take the vaccinations if offered, since it is challenging to determine whether they are protected from re-infections (especially asymptomatic). Based on the interim results, some of the vaccines (from mRNA platforms) came out with remarkably high efficiency (approx. 95%), while another one (from Viral vectors) showed nearly 70%. Main takeaway messages from these studies are, they are efficient in fighting against the disease, it gives nearly 100% protection to the vaccinated from getting a critical disease condition, they are safe and side effects are not significant. Though rapid development was highlighting feature for these authorized vaccines, the data show that they have not compromised any safety regulations during these processes, and the efficiency of these novel-platform vaccines is unprecedented. 

More vaccines in the pipeline

More than 100 vaccine candidates developed using various classical and novel platforms, are undergoing different stages of clinical phase trials (nearly 20 are in the final clinical phases). Among these currently 3 (with peer-reviewed data) got Emergency Use Authorization (EUA) in multiple countries and millions in the priority groups are taking it. To jab billions of people (at least two times, because of 2 dose regimen) around the world, we need different safe and efficient vaccines. Those authorized vaccines have completed only a few months of the 2-year clinical-trial period. So, anyone received the vaccine will be monitored for any-yet unobserved signs of concern. In case of any drawbacks reported on the authorized vaccines on some populations, it is better to be equipped with alternative vaccine options in our catalogue. As long as the vaccine is approved for safety and efficacy (lead runners have exceptionally high efficiency in protecting from severe illness)- if offered, it is wiser to take it.

References

Rapid vaccines

https://www.nature.com/articles/d41586-020-03626-1

https://www.who.int/immunization/research/vaccine_pipeline_tracker_spreadsheet/en/

Pfizer vaccine

https://www.nejm.org/doi/full/10.1056/NEJMoa2034577

Moderna Vaccine

https://www.nejm.org/doi/full/10.1056/NEJMoa2035389?query=recirc_mostViewed_railB_article

Oxford/AstraZeneca vaccine

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext

Covaxin Bharat Biotech

Vaccine approval

https://www.nature.com/articles/d41586-020-03542-4

https://www.nature.com/articles/d41586-020-03593-7

Side effects

https://www.sciencemag.org/news/2020/12/suspicions-grow-nanoparticles-pfizer-s-covid-19-vaccine-trigger-rare-allergic-reactions

https://www.cdc.gov/mmwr/volumes/70/wr/mm7002e1.htm?s_cid=mm7002e1_w

Published by Rajeev

Neuroscientist, living in the North, passionate about brain, new molecular tools, viral vectors.

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