Vaccines (Immunotherapy) along with COVID-19 Overview, Types of Vaccines, Adjuvants, Antigen Uptake Mechanism, COVID-19 Mechanism Of Action, and much more.

1. Vaccines (Immunotherapy)
& COVID-19 Overview
Prepared By: RISHAB MALHOTRA
M.PHARM (PHARMACEUTICS)
College: Lloyd Institute Of Management & Technology
Department Of Pharmaceutics
Submitted to: Dr. Chitra Gupta

2. INTRODUCTION
‘What are Vaccines’
Vaccines are biological products which act by reinforcing the immunological
defence of the body against foreign agencies (mostly infecting organisms or their
toxins).1
Vaccines impart ‘active immunity’ which means that it act as antigens (anything
that stimulates immune response) which induce production of specific antibodies
by the recipient himself.1
Antisera and Immunoglobulins impart Passive Immunity- readymade antibodies
(produced by another person or an animal who has been actively immunized) are
transferred.1
To understand it better lets first know about how the immune system works and
what Active and Passive Immunity is.

3. Immunity
Immunity can be defined as a complex biological system endowed with the
capacity to recognize and tolerate whatever belongs to the self, and to recognize
and reject what is foreign (non-self)2.
Types Of Immunity:
A. Innate Immunity
➢ Natural & genetic
➢ Immunity that an organism is born with
➢ This type of Immunity is encoded in one’s genes
➢ Protect organism throughout their life
Innate Immunity comprises 2 lines of defence which is non-specific in nature.
➢ 1st line of defence (External): Skin, tears (lysozymes), Stomach acid.
➢ 2nd line of defence (Internal): Inflammation, fever.

4. B. Adaptive or Acquired Immunity
It forms the 3rd line of defence and posses two key attributes not seen with non-
specific defences: specificity and memory.
Adaptive or Acquired Immunity again comprises of two types of immunity
1. Active Immunity: Immunity to a pathogen that occur following exposure to said
pathogen. The Body may be simulated to produce its own antibodies by.3
I. Having a disease: During the course of the illness, B-lymphocytes develop into
plasma cells that produce antibodies in sufficient quantities to overcome the
infection. After recovery, the memory B-cells produced confer immunity to
future infection by the same antigen.3
II. Having a subclinical infection: Sometimes the infection is not sufficiently
severe to cause clinical disease but can sufficiently stimulate B-cells to
establish immunity.3
Antibodies are disease specific and one type of antibody protect body from only
one disease causing agent. When B-lymphocytes encounter a pathogen, they create
memory cells in addition to antibodies such memory cells formed following primary
infection can recognize the pathogen. Memory can survive for decades, waiting
within the body until pathogen invades again. On second exposure to that pathogen
immune system is robust, quickly addresses that disease causing agent. This forms
the basis of Vaccines.

5. 2. Passive Immunity: It is the transfer of active humoral immunity of ready-made
antibodies. Passive immunity can occur naturally, when maternal antibodies are
transferred to the foetus through the placenta, and it can also be induced
artificially, when high levels of antibodies specific to a pathogen or toxin (obtained
from humans, horses, or other animals) are transferred to non-immune persons
through blood products that contain antibodies, such as in immunoglobulin therapy
or antisera therapy.4
Active artificial acquired immunity (Vaccines): This type of immunity develops in
response to the administration of dead or live artificially weakened pathogens
(vaccines) or deactivated toxins (toxoids). The vaccines and toxoids retain the
antigenic properties that stimulate the development of immunity but they cannot
cause the disease. Many infectious disease can be prevented by artificial
immunization. Active immunization against some infectious disorder gives lifelong
immunity, e.g. diphtheria, whooping cough or mumps. In other infections the
immunity may last for a number of years or only a few weeks before revaccination is
necessary. Apparent loss of immunity may be due to infection with a different strain of
the same pathogen, which has different antigenic properties but causes the same
clinical illness, e.g. viruses that cause common cold and influenza. In older or poorly
nourished individuals, lymphocyte production, specially B-lymphocytes, is reduced and
the primary and secondary response may be inadequate.3

6. Types Of Vaccines
Vaccines are of 3 types:
i. Killed (Inactivated) vaccine: Consist of organisms killed by heat or chemicals.
e.g. IPV vaccine (Inactivated Polio Virus) , Whole cell pertussis vaccine.1
ii. Live attenuated Vaccines: Consist of live bacteria or viruses which have been
rendered avirulent. They nevertheless grow and multiply in the body of the
host to a limited extent. In individual with impaired host defence, e.g.
leukemia, systemic lupus erythematosus, corticosteroid recipient, AIDS and
other immune deficiency state, the limited virulence of the organism in the
live vaccine may be sufficient to cause a disease. e.g. MMR Vaccine, BCG
Vaccine.1
iii. Toxoids: They are modified bacterial endotoxins so that toxicity is lost but
antigenicity is retained. The term ‘vaccine’ is sometimes restricted to
preparations of whole microorganisms and toxoids are enumerated
separately. Tetanus, Diptheria.1

7. Uptake Of Antigen
Exogenous Antigen Processing:

8.  Endogenous Antigen Uptake:

9. Single Shot Vaccines
A single shot vaccine is a combination product of a prime component ‘antigen’ with an
appropriate adjuvant and a microsphere component that encapsulate antigen and provides
the booster immunization by delayed release of the antigen.
It provides effective patient protection, many traditional vaccines require multiple
injections, which results in a costly and inconvenient regimen.

10. Formulation And Manufacturing Of Single Shot Vaccine:

11. Covid-19 Single Shot Vaccine
Vials labelled "COVID-19 Coronavirus Vaccine" and syringe are seen in front of displayed
Johnson&Johnson logo in this illustration taken, February 9, 2021. REUTERS/Dado
Ruvic/Illustration/File Photo

12. In order to increase the therapeutic activity of the single-shot vaccines, adjuvants are
used.
Addition of adjuvants triggers the immune system to become more sensitive to the
vaccine.
Particulate Adjuvants: They form very small particles that can stimulate the immune
system and also enhances the delivery of antigen to immune cells.
1. Alum
• Most commonly used
• Unknown mechanism of action
• Consists of alum salts that are not soluble in water
• Recently used in Hepatitis-B vaccine.

13. 2. Virosome
• They are vehicles that have spherical shape with a phospholipid mono/bi-
layered membrane.
• Inside Virosome, there is a central cavity that holds the therapeutic molecules
such as nucleic acid, proteins, drugs.
• On the surface of virosome there can be different types of glycoprotein.
Virosome.png

14. 3. Cytokines
• They are small proteins that serve as chemical messengers of the immune
system.
• Because of their role in immune responses, some of them have been evaluated
as vaccine adjuvants.
The main types of cell producing cytokines

15. Mucosal Vaccine Delivery System
➢ Mucosal surface area is a major portal for the entry of disease causing
pathogens (bacteria and viruses).
➢ Immunization by mucosal routes may be effective at inducing protective
immunity against mucosal pathogens at their sites of entry.
➢ Efforts have been focused on effective delivery of vaccine antigen to mucosal
sites that facilitate mucosal immune response.
➢ Discovery of safe, effective mucosal adjuvants are also being sought to
enhance the magnitude and quality of immune response.
➢ It has been estimated that 70% of infectious agents enter the host by mucosal
routes.

16. Design and strategies for mucosal delivery:
1. Emulsion type Delivery:
➢ Oil in water
➢ Water in oil
➢ Water in oil in water
➢ Micro emulsions
➢ Nano emulsions
Antigens are dissolved in water then emulsified in oil in the presence of suitable
emulsifying agent.
Controlled release characteristics of an emulsion are determined by factors such as:
Viscosity in oil phase
Oil to water phase ratio and emulsion droplet size
Pros : Slow antigen release.
Cons: Immunogenic response
Local area irritation, sore arm.

17. 2. Liposomes based delivery:
➢ Spherical shaped vesicles
➢ Contains aqueous core enclosed by lipid bi-layer
➢ Often composed of phospholipids
Liposomes.png

18. Preparation of Liposome vaccine delivery:
Depending upon chemical nature, water soluble antigen (protein, peptides, nucleic
acid, carbohydrates, haptens) are entrapped in aqueous core of liposomes.
Lipophilic compounds (Lipopeptides, antigen, adjuvants, linker molecules) are
intercalated into lipid bi-layer.
Antigen and adjuvants can be attached to the surface of liposomes either by
adsorption or stable chemical linking.
Pros
• Easy surface modification
• Synthesis from non-toxic material
• Wide range of antigen entrapment
• Plasticity
Cons
• Stability problem
• Low antigen loading

19. 3. Polymeric Nono Particles (PNPs):
➢ PNPs are submicron colloidal particles.
➢ Because of their size they are preferentially taken up by the mucosa.
➢ Limited doses of antigen are sufficient to induce effective immunization.
➢ Use of nano particles for oral delivery if antigen is suitable because of their
ability to release proteins and to protect them from enzymatic degradation in
GIT.
Polymers used
▪ Biodegradable: Poly Alkyl Cyano-Acrylate (PACA)
▪ Biodegradable: Poly Methyl Metha Acrylate (PMMA)
4. Virosomes: As mentioned previously.

20. 5. Melts in mouth strips:
➢ Quick dissolving films containing immunogens.
➢ It melts into liquid that children and infants will swallow easily.
➢ Rota virus protection vaccine has been created using this technology.

21. Transdermal Vaccine Delivery
➢ Micro needles: Creation of micro pores in stratum corneum.
➢ Velocity based devices: Application of high velocity to puncture skin. E.g. Injector
Tjet device. It can be used in diabetic patients to deliver insulin without
puncturing the skin. Deliver subcutaneous to intra muscular region.
➢ Sonophoresis: (Waves of frequency 20 to 100 KHz) applied.
➢ Ionophoresis: Application of electrical current forms micro pores in stratum
corneum.
➢ Thermal Ablation: Creation of micro channels in stratum corneum upon laser
ablation. It generates micron size small holes in the stratum corneum by selectively
heating small areas of the skin surface to 100˚. Heat is applied for mili-sec so that
heat transfer to tissues is avoided.

22. Vaccines & Current aspects
Dealing with Covid-19
Case fatality rate = 𝒏𝒐. 𝒐𝒇 𝒅𝒆𝒂𝒕𝒉/𝒕𝒐𝒕𝒂𝒍 𝒏𝒐. 𝒐𝒇 𝒄𝒂𝒔𝒆𝒔 × 𝟏𝟎𝟎
Severe Acute Respiratory Syndrome (SARS) (2002)
Bat Civit Human C.F.R = 10%5(Global Data)
Middle East Respiratory Syndrome (MERS-CoV) (2012)
Bat Camel Human C.F.R = 34%6 (Global Data)
COVID-19 or SARS-CoV-2 (2019)
Bat Pangolin Human C.F.R = 1.12% (as per 22nd of May 2021)7(Indian Data)
C.F.R= 2.076% (as per 22nd of May 2021)8(Global Data)

23. Covid-19 Mechanism of action

24. Vaccines Currently being used and
how effective they are

25. References:
1. Tripathi, K., 2007. Essentials of medical pharmacology. 6th ed. New Delhi: Jyapee,
p.879.
2. Encyclopedia of biomedical engineering. Amsterdam. ISBN 9780128051443.
3. Waugh, A. and Grant, A., 2010. Ross & Wilson anatomy and physiology in health and
illness. 11th ed. Edinburgh: Elsevier, p.373.
4. "Vaccines: Vac-Gen/Immunity Types". www.cdc.gov. Retrieved 1st of May 2021.
5. Chan-Yeung M, Xu RH (November 2003). "SARS: epidemiology". Respirology. 8 Suppl
(s1): S9-14. doi:10.1046/j.1440 1843.2003.00518.x. PMC 7169193. PMID 15018127.
6. Middle East respiratory syndrome coronavirus (MERS-CoV) [Internet]. Who.int. 2021
[cited 2 May 2021]. Available from: https://www.who.int/health-topics/middle-east-
respiratory-syndrome-coronavirus-mers#tab=tab_1
7. Coronavirus in India: Latest Map and Case Count [Internet]. Covid19india.org. 2021
[cited 22 May 2021]. Available from: https://www.covid19india.org/
8. Worldometers.info. 2021. COVID Live Update: 166,624,759 Cases and 3,460,618
Deaths from the Coronavirus - Worldometer. [online] Available at:
<https://www.worldometers.info/coronavirus/> [Accessed 22 May 2021].

26. Images’ Sources Cited:
 Reuters. 2021. France approves J&J's Janssen COVID-19 vaccine. [online] Available
at: <https://www.reuters.com/business/healthcare-pharmaceuticals/france-
approves-jjs-janssen-covid-19-vaccine-2021-03-12/> [Accessed 22 May 2021].
 Babar et al., CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via
Wikimedia Commons
 Cusabio.com. 2021. Get an Overview of Cytokines- CUSABIO. [online] Available at:
<https://www.cusabio.com/cytokines.html> [Accessed 22 May 2021].
 <a href="https://commons.wikimedia.org/wiki/File:Liposome.jpg">Kosi
Gramatikoff w:user:kosigrim</a>, Public domain, via Wikimedia Commons
 Roberts, M., 2021. Oxford Covid vaccine 'safe and effective' study shows. [online]
BBC News. Available at: <https://www.bbc.com/news/health-55228422> [Accessed
22 May 2021].

27. Thank You