The document presents an overview of vaccine development for SARS-CoV-2 (COVID-19), discussing the viral structure, various vaccine approaches including protein subunit, DNA, and mRNA technologies, as well as inactivated virus and viral vector vaccines. It highlights challenges faced in vaccine development, statistical data from vaccine trials, and strategies for building vaccine confidence in healthcare facilities. The presentation includes insights into human transmission, global COVID-19 statistics, and clinical trial details for various vaccines.

1. GURU NANAK INSTITUTE OF PHARMACEUTICALSCIENCE & TECHNOLOGY
157/F Nilgunj Road, Panihati, Kolkata: 700114
VACCINE DEVELOPMENT FOR SARS-CoV-2(COVID-19)- A REVIEW.
Presented By,
SAPTARSHI DAS
(B.PHARM.)

2. Presentation Overview
• Introduction
• Understanding The Viral Particle
• Different Approaches for
vaccine development
• Protein Subunit Vaccines
• DNA Vaccines
• mRNA vaccine technology
• Whole inactivated viral particle
technology
• Strategies for building vaccine
confidence in your facility or system
• Challenges faced for vaccine
development

3. Introduction.
• After detailed analysis it was assumed that suspected bat origin was suggested after 96 % genome sequence identity was
demonstrated between SARS-CoV-2 and another coronavirus named Bat-CoV-RaTG13 isolated from bat species which
colonized in a province nearly 2000 km away from Wuhan.
• However, evidence of first human to human transmission became strongly supported after a visit conducted by a WHO
delegation to the city of Wuhan on January 22nd, 2020
• According to the European Centre for Disease Prevention and Control, as of 2nd of July 2021; 183,865,281 cases of
COVID-19 and 3,980,256 deaths have been reported worldwide since 31st December 2019. American continent was
among the ones with highest number of cases (34,580,198) followed by India and Brazil the leading countries (30,502,362
and 18,687,469 respectively)

4. Understanding the Viral Particle.
Fig. 1: Corona Virus structure (Created with
BioRender.com.)
• Being a RNA virus they encode their genetic material using the RNA
molecules, as can also be seen in case of other RNA viruses such as HIV,
influenza virus.
• The coronavirus core particle is further surrounded by an outer membrane
envelope made of lipids (fats) with proteins embedded, within are specific
viral proteins, including the spike (S), membrane (M), and envelope (E)
proteins .
• The spike proteins latch onto human cells, then undergo a structural change
that allows the viral membrane to fuse with the cell membrane. The viral
genes can then enter the host cell to be copied, producing more viruses.
Recent work shows that, like the virus that caused the 2002 SARS outbreak,
SARS-CoV-2 spikes bind to receptors on the human cell surface called
angiotensin-converting enzyme 2 (ACE2).

5. Understanding the Viral Particle Contd.
Fig. 2: Pathway of Viral Entry and
Replication inside the host cell. (Reprinted
from “Coronavirus Replication Cycle”, by
BioRender.com (2020). Retrieved from
https ://app.biorender.com/biorender-
templates)

6. Understanding the Viral Particle Contd.
Serial radiological progression seen with covid-19 pneumonia. (a) Normal posterior-anterior chest radiograph of patient C, a man in his 50s (taken up to 12
months before admission, included here for comparison). (b) AP chest radiograph of patient C when he developed covid-19 pneumonia—taken in the
emergency department (day 0 of admission), showing ground glass opacities in the periphery (outer third of the lung) of both lungs in the mid and lower zones
(white arrows), preservation of lung marking, and linear opacity in the periphery of the left mid zone (black arrow). (c) AP chest radiograph of patient C on day
10 of admission, showing progression to severe covid-19 pneumonia: patient intubated with endotracheal tube, central lines, and nasogastric tube in situ.
Source :- https://www.bmj.com/content/370/bmj.m2426

7. VACCINE PLATFORM ADVANTAGES DISADVANTAGES CLINICALLY APPROVED EXAMPLES
WHOLE INACTIVATED VIRUS
VACCINE
Stronger immune response; Safer
than live attenuated virus
Potential epitope alteration by inactivation
process
Typhoid, Cholera, Hepatitis A virus,
Plague, Rabies, Influenza, Polio
(Salk)
LIVE ATTENUATED VIRUS VACCINE Stronger immune response; Preservation
of native antigen; Mimicking
natural infection
Risk of residual virulence, especially
for immunocompromised people
Measles, Mumps, Polio (Sabin),
Rota virus, Yellow Fever, Bacillus
Calmette–Guerin (BCG), Rubella,
Varicella
VIRAL VECTOR VACCINE Stronger immune response; Preservation
of native antigen; Mimicking
natural infection
More complicated manufacturing
process; Risk of genomic integration;
Response dampened by pre-existing
immunity against vector
EBOLA Virus
SUBUNIT VACCINE Safe and well-tolerated Lower immunogenicity; Requirement
of adjuvant or conjugate to increase
immunogenicity
Pertussis, Influenza, Streptococcus
pneumoniae, Haemophilus influenzae
type b
VIRAL-LIKE PARTICLE VACCINE Safe and well-tolerated; mimicking
native virus conformation
Lower immunogenicity; More complicated
manufacturing process
Hepatitis B virus, Human Papillomavirus
DNA VACCINE Safe and well-tolerated; Stable
under room temperature; Highly
adaptable to new pathogen; Native
antigen expression
Lower immunogenicity; Difficult
administration route; Risk of
genomic integration
NA
RNA VACCINE Safe and well-tolerated; Highly
adaptable to new pathogen; Native
antigen expression
Lower immunogenicity; Requirement
of low temperature storage
and transportation; Potential risk of
RNA-induced interferon response
NA
Different Approaches for vaccine development

8. Protein Subunit Vaccines
• With a total of 13 protein subunit SARS-CoV-2 vaccines entered clinical
trials.
• Rather than injecting a whole pathogen to trigger an immune
response, subunit vaccines (sometimes called acellular vaccines)
contain purified pieces of it, which have been specially selected for
their ability to stimulate immune cells.
• These fragments are incapable of causing disease, so subunit vaccines
are considered very safe.
• Subunit vaccines contain fragments of protein and/or polysaccharide
from the pathogen, which have been carefully studied to identify
which combinations of these molecules are likely to produce a strong
and effective immune response. By restricting the immune system’s
access to the pathogen in this way, the risk of side effects is
minimised. Such vaccines are also relatively cheap and easy to
produce, and more stable than those containing whole viruses or
bacteria.
Novavax a leading company has entered with
its NVX-CoV2373 vaccine.

9. DNA Vaccine
• There are 4 DNA vaccines for SARS-CoV-2 currently under clinical trials.
• In this type of vaccine, a gene from a virus or bacterial is used to stimulate the immune system. When
the DNA vaccine is administered to a patient, their cells' machinery produces a viral or bacterial
protein, which the immune system recognizes as a foreign body. From there, the immune system will
remember the foreign body and can detect it the next time it enters the body, preventing illness.
• All DNA vaccines being tested in clinical trials for COVID-19 use the S protein as the antigen.
• Recently Zydus Cadilla, an Indian Pharmaceutical giant has seeked approval for the first Plasmid DNA
based Covid-19 vaccine.
Source:- https://indianexpress.com/article/explained/explained-
how-zycov-d-works-how-it-is-different-7385000/

10. mRNA Vaccine.
• mRNA vaccines carry genetic material that teaches cells how to make a harmless piece of “spike protein,”
which is found on the surface of the SARS-CoV-2 virus.
• Genetic material from the vaccine is destroyed by our cells once copies of the spike protein are made and
it is no longer needed.
• Cells display this piece of spike protein on their surface, and an immune response is triggered inside our
bodies. This produces antibodies to protect us from getting infected if the SARS-CoV-2 virus enters our
bodies.
• mRNA vaccines do not affect our DNA; mRNA does not enter the cell nucleus.
• mRNA COVID-19 vaccines cannot give someone COVID-19.
• mRNA vaccines are new, but the technology is not. mRNA vaccines have been studied for influenza, Zika,
rabies, and cytomegalovirus (CMV).
• Two vaccines have received FDA Emergency Use Authorizations (EUAs) :
• Pfizer/BioNTech (BNT162b2) – 95% effective (manufacturer data)
• Moderna (mRNA-1273) – 94.5% effective (manufacturer data)
• Both are mRNA vaccines with a 2-dose schedule. People being vaccinated should complete the two-dose
series with the same vaccine product.
• Duration of protection is not yet known.

11. COVID-19 vaccine trials by the numbers
As of December 21, 2020
Pfizer/BioNTech
– 45,302 enrolled
• 43,125 received 2nd dose
– 150 clinical sites
• 39 U.S. states
– Racial/ethnic distribution
• 13% - Hispanic
• 10% - African American
• 6% - Asian
• 1% - Native American
– 40% ages 56-85
Moderna
– 30,000 enrolled
• 25,654 received 2nd dose
– 89 clinical sites
• 32 U.S. states
– Racial/ethnic distribution
• 63% - White
• 20% - Hispanic
• 10% - African American/Black
• 4% - Asian
• 3% - All others
– 64% ages 45 and older
• 39% ages 45-64
• 25% ages 65+
Sources: https://www.pfizer.com/science/coronavirus/vaccine;
https://www.modernatx.com/cove-study
For more information, visit www.clinicaltrials.gov

12. Whole inactivated viral particle technology
Inactivated vaccine
The first way to make a vaccine is to take the disease-carrying virus or bacterium, or one very similar to it, and
inactivate or kill it using chemicals, heat or radiation. This approach uses technology that’s been proven to work
in people – this is the way the flu and polio vaccines are made – and vaccines can be manufactured on a
reasonable scale.
Among all of the ongoing trials of whole inactivated COVID-19 vaccine, there are three of them who have publicly
reported their preclinical or clinical data. SinoVac Inc. developed CoronaVac (also called as PiCoVacc) and Another
from Bharat Biotech also known as Covaxin are approved and used you vaccination drives
However, it requires special laboratory facilities to grow the virus or bacterium safely, can have a relatively long
production time, and will likely require two or three doses to be administered.
Covaxin vial Sinovac

13. Viral Vector Vaccine.
Viral vector vaccines use a modified version of a different virus (the vector) to deliver important instructions to our cells.
1.First, the vector (not the virus that causes COVID-19, but a different, harmless virus) will enter a cell in our body and then use the cell’s
machinery to produce a harmless piece of the virus that causes COVID-19. This piece is known as a spike protein and it is only found on the
surface of the virus that causes COVID-19.
2.Next, the cell displays the spike protein on its surface, and our immune system recognizes it doesn’t belong there. This triggers our immune
system to begin producing antibodies and activating other immune cells to fight off what it thinks is an infection.
3.At the end of the process, our bodies have learned how to protect us against future infection with the virus that causes COVID-19. The
benefit is that we get this protection from a vaccine, without ever having to risk the serious consequences of getting sick with COVID-19. Any
temporary discomfort experienced after getting the vaccine is a natural part of the process and an indication that the vaccine is working.
4.Currently, 12 viral vector vaccines are in clinical trials with an additional 36 viral vector based vaccines under preclinical development
5.AZD1222 developed by AstraZeneca and Oxford University is a chimpanzee adenovirus-based viral vector vaccine (ChAdOx1) and Gamaleya
Research Institute of Russia produced Gam-COVID-Vac (or Sputnik V). Both are approved under emergency protocols,
ChAdOx1 Sputnik-V

14. Strategies for building vaccine confidence in facility or
system
1. Encourage senior leaders to be vaccine champions.
2. Host discussions where personnel at different levels can provide input and ask
questions.
3. Share key messages with staff through emails, breakroom posters, and other
channels.
4. Provide information and resources to healthcare teams about COVID-19
vaccines, how they are developed and monitored for safety, and how teams
can talk to others about the vaccines.
5. Talk to non-medical staff about the importance of getting vaccinated.
6. Make the decision to get vaccinated visible and celebrate it!
Photo credit: Dr. Anthony Fauci after
receiving the vaccine dose. National
Foundation for Infectious Diseases

15. Challenges faced for vaccine development

16. References.
• Centers-for-Disease-Control-and-Prevention. Human Coronavirus Types. 2020.
https://www.cdc.gov/coron aviru s/types .html.
• van der Hoek L. Human coronaviruses: what do they cause? Antivir Ther. 2007;12(4 Pt B):651–8.
• World-Health-Organization. Coronavirus disease (COVID-19) pandemic. Geneva: World-Health-
Organization; 2020b.
• Moderna’s COVID-19 Vaccine Candidate Meets its Primary Efficacy Endpoint in the First Interim
Analysis of the Phase 3 COVE Study. Moderna,2020. https ://investors.moder natx.com/news-
releases/news-releasedetails/modernas-covid -19-vaccine-candidate-meets -its-primary-efficacy.
• Pfizer and BioNTech Conclude Phase 3 Study of COVID-19 Vaccine Candidate, Meeting All Primary
Efficacy Endpoints. Pfizer, 2020. https ://www.pfize r.com/news/press -release/press -release-detai
l/pfize r-andbiontech-concl ude-phase -3-study -covid -19-vaccine.
• The-New-York-Times. AstraZeneca Pauses Vaccine Trial for Safety Review. 2020
• http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=51254&EncHid=&userName=ZyCoV-D
• Second Interim Analysis of Clinical Trial Data Showed a 91.4% Efficacy for the Sputnik V Vaccine on
Day 28 After the First Dose; Vaccine Efficacy is Over 95% 42 Days After the First Dose. Sputnik V, 2020.
https://sputn ikvac cine.com/newsr oom/press relea ses/secon d-inter im-analysis-of-clinical-trial -
data-showe d-a-91-4-efficacy-for-the-sputnik-v-vaccine-on-d/.
• Wang N, Shang J, Jiang S, Du L. Subunit vaccines against emerging pathogenic human coronaviruses.
Front Microbiol. 2020;11:298.

17. Thank You.