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A Microbiological Deconstruction of Life Saving Vaccines

The whole world is well into the 2^nd year of the coronavirus pandemic and India specifically saw a huge bump in its number of cases in early February, termed to be the second wave. The first wave’s trend slowed down in November after reaching the peak in September 2020. After several months of testing and trials, the first vaccine jab was given to an Indian sanitation worker in mid-January. The overall first phase of giving the vaccines to the frontline and healthcare workers was a brilliant idea, but in hindsight was again let down by humanity’s selfishness and greed, with the already slow supply. At which point people too stopped following safety precautions, and the government too, let its guard down in search of political benefits. So, we entered the second wave and reached higher peaks than last year where the whole country was sent into a frenzy to get a jab by hook or by crook.

But most people don’t know that even before this pandemic hit, India was the leading vaccine supplier in the whole world, so our pharmaceutical companies are capable of unprecedented results.

So, let’s check out how these three vaccines, Covaxin, Covishield, and the newly released Sputnik V work, in biochemistry language.

Covaxin –

Covaxin was developed by an Indian pharmaceutical company Bharat Biotech in collaboration with the Indian Council of Medical Research, a government-funded biomedical research institute, and it’s subsidiary the National Institute of Virology. Bharat Biotech is a renowned name in the vaccine business, which brought to market 16 original vaccines, including rotavirus, hepatitis B, Zika virus, and chikungunya.

Now its latest creation, Covaxin, is based on the same technology as Sinovac and Sinopharm developed and circulated widely by China, which is an inactivated virus. It uses the complete infective SARS-CoV-2 viral particle consisting of RNA surrounded by a protein shell but modified so that it cannot replicate. So, in simple words, the same virus which it is going to fight is the one introduced in our systems to generate immunity against it, if it enters our body.  The same technology has been used for many years for several epidemic diseases, like polio, Rabies, Typhoid, Cholera, etc.

Covaxin comes as a two-dose regimen, recommended to be taken 28 days apart, which is now increased to more than 90 days due to a shortage in supply. This is because inactivated viruses tend to produce a weaker response by the immune system than live viruses, immunologic adjuvants, and multiple “booster” injections may be required to provide an effective immune response against the pathogen. This means even after both doses people can still be affected by coronavirus but it’ll be less intense and harmful.

The vaccine can be stored at 2 to 8 degrees celsius. The vaccine has an efficacy rate of 81%, preliminary data from its phase 3 trial shows.

India’s regulators gave the vaccine an emergency approval in January while the third phase of the trial was still underway, sparking skepticism and questions from experts saying how an incomplete studied vaccine can be approved for the general public. Their questions were logical and received a response in defense from the company that it was safe and provides a robust immune response.

Covishield –

Next is Covishield, which was developed in collaborative efforts of Oxford University and AstraZeneca, the British-Swedish pharmaceutical company. The Oxford-AstraZeneca vaccine (sold under the brand names Covishield and Vaxzevria among others) is being manufactured locally by the Serum Institute of India (SII), the world’s largest vaccine manufacturer.

Covishield is made from a weakened and harmless version of a common cold virus (replication-deficient simian vector known as an adenovirus) from chimpanzees. The final product contains the spike protein found in SARS-CoV-2. When that protein reaches the body’s cells, the immune system mounts a defense, creating antibodies and memory cells to protect against an actual SARS-Cov2 infection. So it has been modified to look more like coronavirus. This use of living attenuated microorganisms, or living fully virulent organisms that are administered to produce or artificially increase immunity is called the viral vector method or carrier vaccine. It also needs 2 doses in 4-12 weeks, while the handling temperature is again 2-8 degrees Celsius.

AstraZeneca recently updated its data analysis of its phase 3 trials in March, showing its vaccine to be 76% effective at reducing the risk of symptomatic disease 15 days or more after receiving the two doses, and 100% against severe disease. The company also claims that the vaccine was 85% effective in preventing COVID-19 in people over 65.

Now the vaccine has a brilliant safety profile, but it came under attack in mid-April when the UK Medicines and Healthcare products Regulatory Agency (MHRA) reported 268 cases of rare anaphylaxis in receivers out of some 21.2 million vaccinations. And in very rare cases, around 1 in 1,00,000 the receiver can inhibit the increased risk of blood clots in combination with low levels of blood platelets. The full reports of these incidents are awaited.

Sputnik V –

Last is Sputnik V, the latest approval/release in the vaccine category in India. As the name suggests, it’s developed by Russian based institute named Gamaleya Research Institute of Epidemiology and Microbiology and registered by the Russian Ministry of Health in August 2020 and after several rounds of trials was approved by 59 countries including India in April 2021.

The functioning is practically the same as Oxford-AstraZeneca Covishield. Gam-COVID-Vac is also a viral two-vector vaccine based on two human adenoviruses types 26 and 5 containing the gene that encodes the full-length spike proteins of SARS-CoV-2 to stimulate an immune response. The two vaccines were modified to remove the E1 gene to keep it from replicating, hence, the Ad26-based vaccine is used on the first day and the Ad5 vaccine is used on the 21st day to boost immune response.

Approval in early August of Gam-COVID-Vac/Sputnik V was met with criticism and controversy in mass media and discussions in the microbiology community as to whether approval was justified in the absence of robust scientific research confirming safety and efficacy or was just a marketing gimmick for the authoritarian government. But in February 2021, the analysis from the trials was presented henceforth in medical research papers where the efficacy was indicated to be 91.6% without any significant side effects. The storage temperature is the same 2-8 degrees Celsius.

Others –

Apart from these three, several countries are developing their versions of the Covid-19 vaccines based on their body structure, immunity levels, climate, etc. Here are a few already released (not yet in India) or upcoming vaccines/immunity boosters to the Covid virus –

1. CoronaVac

Type/Mechanism – An inactivated vaccine (formalin with alum adjuvant)
Country of Origin – China
Developers – Sinovac
Efficacy – 65%
Storage – 2-8 degree Celsius
Doses – 2

2. Comirnaty

Type/Mechanism – mRNA
Country of Origin – United States
Developers – Pfizer–BioNTech
Efficacy – 91.3%
Storage – (-80) – (-60) degree Celsius
Doses – 2

3. Moderna

Type/Mechanism – mRNA
Country of Origin – United States
Developers – Moderna
Efficacy – 94.1%
Storage –  2-8 degree Celsius
Doses – 2

4. Janssen

Type/Mechanism –  Viral vector
Country of Origin – Netherlands/United States
Developers – Janssen Pharmaceuticals/Johnson & Johnson
Efficacy – 85%
Storage – 8-25 degree Celsius
Doses – 1

4. BBIBP-CorV

Type/Mechanism – Inactivated vaccine
Country of Origin – China
Developers – Beijing Institute of Biological Products
Efficacy – 86%
Storage – Normal refrigerated temperature
Doses – 2

5. EpiVacCorona

Type/Mechanism – Peptide vaccine
Country of Origin – Russia
Developers – Federal Budgetary Research Institution State Research Center of Virology and Biotechnology
Efficacy – NA
Storage – NA
Doses – NA

6. Convidicea

Type/Mechanism – Recombinant vaccine/Viral vector
Country of Origin – China
Developers – CanSino Biologics
Efficacy – 65.7%
Storage – 2-8 degree Celsius
Doses – 1

7. WIBP-CorV

Type/Mechanism – Inactivated vaccine
Country of Origin – China
Developers – Wuhan Institute of Biological Products / Sinopharm
Efficacy – 72.5%
Storage – 2-8 degree Celsius
Doses – 2

8. CoviVac

Type/Mechanism – Inactivated vaccine
Country of Origin – Russia
Developers – Chumakov Federal Scientific Center for Research and Development of Immune and Biological Products
Efficacy – NA
Storage – 2-8 degree Celsius
Doses –

9. ARCoV

Type/Mechanism – mRNA-based vaccine
Country of Origin – China
Developers – Walvax Biotechnology Co. Ltd.; Abogen Biosciences Co. Ltd.; Yuxi Walvax Biotechnology Co. Ltd.
*In Development.
More information to be available soon.

10. NVX-CoV2373

Type/Mechanism – Nanoparticle vaccine
Country of Origin – United States
Developers – Novavax
*In Development.
More information to be available soon.

11. ZyCoV-D

Type/Mechanism – DNA vaccine (plasmid)
Country of Origin – India
Developers – Zydus Cadila
*In Development.
More information to be available soon.

12. Abdala

Type/Mechanism – Protein subunit vaccine
Country of Origin – United Nations
Developers – Center for Genetic Engineering and Biotechnology
*In Development.
More information to be available soon.