Immunotherapy and vaccine

Group members: Bùi Đình Chiến BI11-046

Lưu Mộc Linh Hương BI11-109
Tô Minh Nhật BI11-208
Nguyễn Thị Hà Trang BI11-268
Nguyễn Hải Hoàng BI11-098

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Table of contents

I
Immunotherapies classification
II
Vaccines as a part of human life
III
Covid 19 vaccines, past - present and future
IV
Immunotherapy for allergies
V
Immunotherapy for cancer

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 Definition
Immunotherapy or biological therapy is
the treatment of disease by activating
or suppressing the immune system.

Classification:

● Activation immunotherapies : designed to elicit or

amplify an immune response
● Suppression immunotherapies: designed to reduce or
suppress

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Activation immunotherapies can be achieved by:

Active Passive
01 immunotherapy 02 immunotherapy

Adoptive Cell based

03 immunotherapy 04 immunotherapy

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1. Active immunotherapy : type of immunotherapy that aims to stimulate the
host's immune system or a specific immune response to a disease or pathogen

● · Non-specific active immunotherapy:

generating a general immune system response
using cytokines and other cell signaling
molecules

● · Specific active immunotherapy:

the generation of cell-mediated and antibody
immune responses focused on specific
antigens expressed by the cancer cells,
typically using a vaccine platform
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Cytokines

● Small protein- cell signaling

● Involved in autocrine, paracrine,endocrine

signaling
-> immunomodulating agents

● Include: chemokines, interferons, interleukins,

lymphokines, tumour necrosis factor

● Produced by broad range of cells

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Vaccine
Contain a weakened or an inactivated (killed) form of a virus
or bacterium, or a small part of the virus or bacterium

-> antigen.

When a person gets a vaccine -> activates the immune cells

so that they kill the disease-causing virus or bacterium and
make antibodies against it.

Activates immune cells - called T-cells and B-cells - in the

blood, in the bone marrow and throughout the body.

If the person comes into contact with the actual virus or

bacterium, their immune system will remember it.

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 Adjuvant therapy

Also known as adjunct therapy, adjuvant

care, or augmentation therapy, is a therapy
that is given in addition to the primary or
initial therapy to maximize its effectiveness.

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2. Passive immunotherapy: is the transfer of active humoral immunity of ready-made
antibodies

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3. Adoptive immunotherapy provide the patient’s body with primed specific lymphocytes

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4. Cell based immunotherapy: make the immune cells work together to
defend the body against cancers and attack by foreign and non-self invaders such as
bacteria and viruses

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 Suppression
immunotherapy
Immune suppression dampens an abnormal immune response in autoimmune diseases or reduces
a normal immune response to prevent rejection of transplanted organs or cells.

Immunosuppressive drugs Immune tolerance

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Immunosuppressive drugs: Immunosuppressive drugs help manage organ
transplantation and autoimmune disease. Immune responses depend on lymphocyte proliferation

● Cytostatic drugs: immunosuppressive

● Glucocorticoids: more specific inhibitors of lymphocyte

activation

● Immunophilins : specifically target T lymphocyte activation

● Other drugs : modulate immune responses and can be used

to induce immune regulation

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Immune tolerance

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Vaccines as a part
of human life

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 Definition

- Vaccine: biological preparation provide

antigenic stimulus to induce long -
lasting, productive immunity.
- Vaccination: The administration of
vaccines.

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Principles and Effects of Vaccination
- The adaptive immune response is mediated by B cells that produce antibodies
(humoral immunity) and by T cells (cellular immunity).
- Mainly confer protection through the induction of antibodies.
- Sterilizing immunity means that the immune system is able to stop a pathogen,
including viruses, from replicating within your body. → Long-term immunity.

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Principles and Effects of Vaccination

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Types of Vaccines

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Live, attenuated vaccine
- Reducing the virulence of a pathogen, but
still keeping it "live".
- Will not enough to cause illness, but will still
provoke an immune response that can
protect against future infection.
- Similar to the natural infection → create a
strong and long-lasting immune response.
- Protection from a live, attenuated vaccine
typically outlasts the protection provided by
a killed or inactivated vaccine.

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Ideal properties of attenuated vaccine
- Accurately imitate natural infections.
- Are effective at evoking both strong antibody and cell-mediated immune reactions.
- Can elicit long-lasting or life-long immunity.
- Often only one or two doses are required.
- Quick immunity onset.
- Cost-effective (compared to some other health interventions).
- Can have strong beneficial non-specific effects.

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Killed or inactivated vaccine
- Created by inactivating a pathogen, typically using heat or chemicals such as
formaldehyde or formalin.
- Provide shorter protection than live vaccines, and are more likely to require boosters
(adjuvants) to create long-term immunity.
- Inactivated vaccines exist for many pathogens, including influenza, polio (IPV), rabies,
hepatitis A and pertussis.

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Toxoid
- Are inactivated toxins at a toxin
produced by pathogen.
- They require a series of injections for
full immunity, followed by boosters
every 10 years
- The best examples for toxoid vaccines
were against diphtheria and tetanus.

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Subunit Vaccines
- Contain only pieces of the pathogens they
protect against.
- .Subunit vaccines use only part of a target
pathogen to provoke a response from the
immune system.
+ Isolating a specific protein from
a pathogen and presenting it as
an antigen on its own.
+ Genetic engineering
- Example: pertussis, influenza, hepatitis B,
HPV

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Conjugated Vaccines
- Contain only pieces of the pathogens
they protect against.
- Have been developed in recent years to
deal with the poor immune response of
children to vaccines.
- Examples of the conjugate vaccines
include influenza vaccine (HiB), for
pneumococcal and meningococcal.

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Polysaccharide Vaccines

Unique type of inactivated subunit vaccine composed of

long chains of sugar molecules that make up the surface

capsule of certain bacteria.

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Covid-19
Vaccine
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Our process

Step 1 Overview of SARS-CoV-2 Virus

Step 2 Immunopathophysiology of
Covid-19

Step 3 Overview of Mechanism and

Classification of Covid-19 Vaccine

Step 4 Close look about Nucleic

Acid-Based Vaccine

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1. Overview of SARS-CoV-2 virus

Genome Protein N
+ssRNA Nucleocapsid Protein

Protein M
Membrane Protein

Protein S Protein E
Spike Protein Envelope Protein

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 SARS-CoV-2 structural elements, genetic makeup and viral life cycle overview.
(A) Structural organization of novel coronavirus; (B) Genomic Map of the novel coronavirus; (C)
Lifecycle of novel coronavirus 30
 2. Immunopathophysiology of COVID-19

5%
80% SARS-CoV-2 infected cases
require ventilation

15%
SARS-CoV-2 infected cases
are asymptomatic or mild

SARS-CoV-2 infected cases

require oxygen supply 31
 The
immunopathology
of COVID-19

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3. Overview of Mechanism
and Classification of
Covid-19 Vaccine
Question: How Do Vaccines Work?

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 Spike

Overview: How Do Vaccines Work?

- SARS-CoV-2 is the virus that causes COVID-19. The spike protein on the surface of
SARS-CoV-2 is an example of an antigen

- Vaccines are the best way to train our immune system to recognize viruses, or pieces of
viruses, called antigens. Our immune system creates antibodies and other defenses to
protect us.

- When a vaccinated person is exposed to SARS-CoV-2, their immune system will recognize
the viral antigens and spring into action to keep them healthy.

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Types of Vaccine
Platforms
There are two categories of COVID-19
Vaccines: Whole Virus Vaccines and
Component Viral Vaccines .

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Whole Virus Vaccines

Inactivated
Contains copies of the virus that
have been killed (inactivated)

Component Viral Vaccines

Contains copies of the virus that
have been weakened (attenuated)

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 Component Viral Vaccines

Protein Subunit Virus-like Particles Non-Replicated Viral Vector

Contains isolated and Contains viral proteins that Contains viral genetic material
purified viral proteins mimic the structure of the virus, packaged inside another harmless
but no genetic material virus that cannot copy itself

Replicating
Viral Vector DNA-based RNA-based
Contains viral genetic material Contains viral genetic material
Contains viral genetic material
which provides the instructions for which provides the instructions for
packaged inside another harmless
making viral proteins making viral proteins
virus that can copy itself
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 4. Close look about
Nucleic Acid-Based
Covid-19 Vaccine

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 Mechanism of
nucleic acid
vaccine to
generate immune
protection
post-vaccine jab

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2 famous vaccine use that technics and
how they trigger the immune system

Country: USA
71% Moderna
Pfizer& BioNTech

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Moderna/USA:
RNA-based

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 Pfizer &
BioNTech/USA:
RNA-based
(Encodes a
prefusion
stabilized,
membrane-anchor
ed SARS-CoV-2
full-length Spike
protein)

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Immunotherapy
for allergies

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 Definition
- Allergies: Hypersensitivity of immune
system to harmless substances

- Allergen immunotherapy:
Desensitization by giving gradually
increasing doses of the allergen
-> change immune response

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 Mechanism

− Reduce the IgE-dominated response,

increase levels of IgG
− Increase levels of IL-10 and TGF-β
− Shift from Th2 to Th1 immune responses

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 Tests before treatment

− Skin test: putting a drop of liquid on the

forearm (substance may be allergic to)

− Blood test: Total IgE & Specific IgE test

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 Types of
allergy immunotherapy

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 Allergy shots

− Also subcutaneous immunotherapy

(SCIT)
− Regular injections over a period of time
− 2 phases:
Build up & maintenance phase

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 Sublingual
immunotherapy

− Liquid drops or a tablet of allergen

extracts

− Higher doses are required and can

be very expensive

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 Oral immunotherapy
− OIT involves feeding increasing amounts of a
food allergen
− Palforzia: the first OIT approved by FDA in
2020

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 Transdermal immunotherapy

− Skin-induced suppression via epicutaneous

application
− Treat perennial, seasonal and pet allergies
− Experimental models to treat autoimmune
diseases

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 Helminthic therapy
− Also an experimental type of immunotherapy
− Regular inoculation of the patient with specific parasitic
intestinal nematodes or other helminths

Proposed mechanism of action:

− Secrete immunoregulatory molecules -> promote induction of
regulatory T cells
− Th1 pro-inflammatory response -> Th2 response with reduced
inflammation
− Decrease levels of IL 12 and IFNy, and increase in the
regulatory T cells, IL 4, 5 and 10.

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Immunotherapy for
cancer

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 Immunotherapy for cancer
Goals of immunotherapy for cancer
● Aid in the recognition of cancer as foreign by the immune system
● Stimulate immune responsiveness
● Relieve inhibition of the immune system that allows tolerance of
tumor growth

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Three E theory : Cancer’s immunoediting

● Elimination: The immune system detects and destroy cancer

cells.
● Equilibrium: Cancer cells exist in a delicate balance between
growth and control by the immune system.
● Escape: The disruption of the equilibrium that leads to
Immunosuppression.

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 Three main approaches to cancer
immunotherapy
● Active immunization ( cancer vaccines )
● Adoptive cell transfer - CAR T cells
● Non-specific stimulation of immune reactions

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 1. Cancer vaccines

● Keep the cancer from coming back

● Destroy any cancer cells still in the body after treatments end
● Stop a tumor from growing or spreading

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 HBV and HPV vaccines
The vaccines for prevent certain viral infections:
● Hepatitis B (HBV)
● Human papillomavirus (HPV)

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 Two FDA - approved vaccine

● Sipuleucel - T (Provenge®), which is used for prostate cancer

that has metastasized (spread)
● T-VEC (Imlygic®), which is used to treat advanced melanoma
that cannot be completely removed with surgery

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 Sipuleucel-T production

● Isolating autologous peripheral blood mononuclear cells

(PMBCs) through leukapheresis.
● Ex vivo culturing: PA2024 (a recombinant fusion protein
composed of PAP linked to granulocyte-macrophage
colony-stimulating factor.
● Full treatment regimen: approximately 2-week intervals.

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 Sipuleucel-T mechanism of action
● Increase in APC activation
● Prostatic acid phosphatase (PAP) - an antigen that is highly
expressed in most prostate cancer cells
● Stimulation of cytotoxic T-lymphocyte activity
● Antigen spread
● Increasing cytotoxic T-cell activity

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 Talimogene laherparepvec (T-VEC)
● Oncolytic viral immunotherapy
● Local treatment of unresectable metastatic stage melanoma
● Local and systemic immunologic responses leading to tumor
cell lysis
● Release of tumor-derived antigens and subsequent activation
of tumor-specific effector T cells
● This immunostimulatory agent successfully synergizes with
immune checkpoint inhibitors

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T-VEC mechanism of actions

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2. Chimeric antigen receptor (CAR) T cells
● Chimeric antigen receptor (CAR) T-cell therapy is a way to get
immune cells called T cells (a type of white blood cell) to fight
cancer
● Cell-based gene therapy: altering the genes inside T cells to
help them attack the cancer

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 CAR-T cells advantages
● MHC - independent recognition of malignant cells
● A large number of polyclonal T cells
● Targeted therapy => fewer side effects

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3.Non-specific stimulation of
immune reactions

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 3.1 Stimulate effector cells

● Interleukin-2 (IL-2) :
○ Cytokines with pleiotropic effects on immune system
○ Produced predominantly by antigen-simulated CD4+ T
cells
○ Promote CD8+ T-cell and NK cell cytotoxicity activity
○ Modulate T-cell differentiation programs in response to
antigen
○ Promoting naive CD4+ T-cell differentiation into Th1, Th2
cells while inhibiting Th17 differentiation

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 Inhibit regulatory factors
● CTLA -4 (cytotoxic T lymphocyte antigen 4): the cDNA for a
T-cell expressed, CD28-related molecule
● PD-1: A protein found on T cells that helps keep the body’s
immune responses in check
● The 2018 Nobel Prize in Physiology or Medicine was jointly
awarded to James P.Allison and Tasuku Honjo for their
discovery of cancer therapy by inhibition of negative immune
regulation

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 References
1. American Cancer Society. How immunotherapy is used to treat cancer.
https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/wh
at-is-immunotherapy.html. Accessed on September 2, 2020.
2. Anassi E, Ndefo UA. 2011;36(4):197-202.
3. Cancer Research Institute. New report charts dramatic growth in the global clinical trial landscape for
PD-1/L1 immune checkpoint inhibitors.
https://www.cancerresearch.org/news/2018/pd-1-l1-checkpoint-inhibitor-landscape-analysis.
Accessed on September 2, 2020.
4. Cancer Research Institute. PD-1/PD-L1 Landscape.
https://www.cancerresearch.org/scientists/immuno-oncology-landscape/pd-1-pd-l1-landscape.
Accessed on September 2, 2020.
5. Chaudhari PB.. Indian J Med Paediatr Oncol. 2017;doi:10.4103/ijmpo.ijmpo_193_16.
6. Chemocare. Pembrolizumab. http://chemocare.com/chemotherapy/drug-info/Pembrolizumab.aspx.
Accessed on September 2, 2020.
7. Conry RM, et al. Hum Vaccin Immunother. 2018;doi:10.1080/21645515.2017.1412896.
8. Diagnostics PT. Proleukin (Aldesleukin). https://www.proleukin.com/. Accessed on September 2,
2020.
9. FDA approves second CAR T-cell therapy. Cancer Discov.
2018;doi:10.1158/2159-8290.CD-NB2017-155.
10. Finkelmeier F, et al. Expert Rev Anti-cancer Ther. 2018;doi:10.1080/14737140.2018.1535315.
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