This document discusses five main types of vaccine technologies: live-attenuated vaccines, inactivated vaccines, subunit vaccines, viral vector vaccines, and messenger RNA (mRNA) vaccines. For each technology, it provides examples of existing vaccines and candidates in development for COVID-19. Live-attenuated vaccines contain weakened live pathogens, while inactivated vaccines use killed whole pathogens. Subunit vaccines contain fragments of pathogens, and viral vector vaccines use harmless viruses to deliver genetic code for antigens. mRNA vaccines teach the body to produce protein antigens to trigger immunity. The Pfizer and Moderna COVID-19 vaccines are mRNA-based.

1. Mechanisms of Different Type
of Vaccines in development
By: Emilio Molina & Germain Alanis

2. Objectives
• Recap of certain vaccines technologies against
Covid-19
• Introduce MOA of current and in development
Covid-19 vaccines

3. Understanding Five Types of Vaccine
Technologies
• Ever since the first vaccine was developed in 1796 to treat
smallpox, several different methods have been created to develop
successful vaccines. Today, those methods, known as vaccine
technologies, are more advanced and use the latest technology to
help protect the world from preventable diseases.
• Depending on the pathogen (a bacteria or virus) that is being
targeted, different vaccine technologies are used to generate an
effective vaccine.
• In total, there are five different vaccine technology platforms in this
presentation each with its own benefits, and examples.

4. Vaccine technology platforms
• Live-attenuated vaccines
• Inactivated vaccines
• Subunit vaccines
• Viral vector vaccines
• Messenger RNA (mRNA) vaccines

5. Live-attenuated vaccines
• Live-attenuated vaccines contain live pathogens from either a
bacteria or a virus that have been "attenuated," or weakened.
• They are produced by selecting strains of a bacteria or virus that
still produce a strong enough immune response but that does not
cause disease. Attenuated viruses were one of the earliest
methods of eliciting protective immune responses
• Benefits: Because these types of vaccines contain a live
pathogen, the immune system reacts very well to them and it will
typically remember the pathogen for a very long time. Additional
doses, or booster shots, are not always needed.
• Examples: Measles, mumps, and rubella (MMR) vaccine, varicella
(chickenpox) vaccine

6. Live-attenuated vaccines for
COVID-19
• Currently, there is no WHO-approved COVID-19 live attenuated
vaccine for emergency use. Two candidate COVID-19 live
attenuated vaccines, COVI-VAC and MV-014-212 (Meissa
Vaccine), have been approved for clinical trials as of March 28,
2022.
• Both are still in Phase 1 clinical trials.
• COVI-VAC is being developed as an intranasal COVID-19 vaccine.
• COVI-VAC is attenuated through removal of the furin cleavage site
and introduction of 283 silent, degrading mutations that maintain
viral amino acid sequence but slow viral replication in vivo by up to
5 logs.
• Live attenuated vaccines induce extensive responses, including
innate, humoral, and cellular immunity against viral structural and
nonstructural proteins in the recipient.

7. Inactivated vaccines
• Inactivated vaccines are produced by inactivating the in vitro
cultured viruses using chemical reagents
• An advantage of inactivated vaccines is using the entire virus as an
immunogen, and compared to vaccines of protein fragments, they
produce a wider range of antibodies.
• Wang et al. introduced the manufacturing process of the SARS-
CoV-2 inactivated vaccine by using β-propiolactone to inactivate
the virus that was obtained from patient swabs and isolated .
• Benefits: Inactivated vaccines can be mass-produced and no
deaths have been reported in clinical trials, indicating their good
safety.

8. Inactivated vaccines for COVID-
19
• A total of 21 candidate COVID-19 inactivated vaccines have been
approved for clinical trials as of March 28, 2022
• The Sinovac and CoronaVac inactivated vaccines approved by
WHO are independently developed in China.
• CoronaVac current effectiveness is approximately 65.9% for the
prevention of Covid-19, 87.5% for the prevention of
hospitalizations, 90.3% for the prevention of ICU admissions, and
86.3% for the prevention of Covid-19-related deaths

9. Subunit vaccines
• Subunit vaccines are made from a piece of a pathogen, not the
whole organism, and they do not contain any live pathogens. Some
important subunit vaccines are polysaccharide vaccines, conjugate
vaccines, and protein-based vaccines.
• Polysaccharide vaccines target an immune response to pathogenic
bacteria that are encased in a layer of sugar. This means they help
you make protective responses against the surface of the bacteria,
allowing your body to kill the bacteria.
• Conjugate vaccines are the same in that they have a
polysaccharide component, but that sugar is stuck to a protein so
your immune system will respond to the sugar on the bacteria
better.

10. Subunit vaccines
• Protein-based vaccines allow you to make a protective response
against a protein on the surface of a virus, against a protein on the
surface of a bacteria, or against a secreted toxin. In this case, the
immune response is against the protein components of the bacteria
or virus, not the sugar coat.
• Subunit vaccines can be made one of two ways: from the original
pathogen or recombinantly. Recombinant vaccines use another
organism to make the vaccine antigen.

11. Subunit Vaccines
• Benefits: Subunit vaccines only contain pieces of a pathogen, not
the whole organism, so they cannot make you sick or cause
infection. This makes them suitable for people who should not
receive “live” vaccines, such as young children, older people, and
immunocompromised people.
• Examples: Haemophilus influenzae type B (Hib) vaccine
(conjugate), pneumococcal vaccine (polysaccharide or conjugate),
shingles vaccine (recombinant protein), hepatitis B (recombinant
protein), acellular, NOVAVAX (USA)

12. NOVAVAX (In development)
• NVX-CoV2373 from the USA uses protein
subunits of the virus. These protein-based
vaccines use harmless protein fragments
or protein shells that mimic the Covid-19
virus spike protein to safely generate an
immune response.

14. Viral vector vaccines
• Viral vector vaccines use a harmless virus to deliver to the host's
cells the genetic code of the antigen you want the immune system
to fight. They are basically a gene delivery system. In doing so,
information about the antigen is delivered, which triggers the body’s
immune response.
• Benefits: Viral vector vaccines usually trigger a strong immune
response. Typically, only one dose of the shot is needed to develop
immunity. Boosters may be needed to maintain immunity.
• Examples: Ebola vaccine, COVID-19 vaccine (AstraZeneca and
Johnson & Johnson)

15. AstraZeneca and Johnson & Johnson
• The AstraZeneca vaccine uses a modified chimpanzee DNA
adenovirus, which has not been exposed to human populations
and does not generate an immune response to the adenovirus
itself, but only to the viral protein encoded in the host DNA.

17. Messenger RNA (mRNA)
vaccines
• One of the newest and most exciting areas in vaccine technology.
mRNA vaccines can be developed quickly using the pathogen’s
genetic code. mRNA is likely to be at least one of the waves of the
future for vaccines.
• When an mRNA vaccine is delivered, the RNA material teaches
our body how to make a specific type of protein that is unique to the
virus, but does not make the person sick. The protein triggers an
immune response, which includes the generation of antibodies that
recognize the protein. That way, if a person is ever exposed to that
virus in the future, the body would have the antibodies to fight
against it.

18. Messenger RNA (mRNA)
vaccines
Benefits: It is a very powerful technique to be able to create a lot of a
vaccine fast. The benefit is that the technology is very adaptable. We
can potentially go in and change the mRNA in the formulation to target
a new antigen and can make a lot of high-quality vaccine material
relatively quickly.
Examples:Pfizer-BioNTech and Moderna COVID-19 vaccine

19. Pfizer-BioNTech and Moderna
• The SARS-CoV-2 contains 25–28 proteins but the researchers just
isolated the mRNA from the spike protein which shows 3 copies of
the same protein, then only one mRNA is produced.

21. References
● Centers for Disease Control and Prevention. (2016, November 22).
Vaccines and preventable diseases. Centers for Disease Control and
Prevention. Retrieved November 28, 2022, from
https://www.cdc.gov/vaccines/vpd/index.html
● Centers for Disease Control and Prevention. (n.d.). Understanding mRNA
COVID-19 Vaccines. Centers for Disease Control and Prevention.
Retrieved November 28, 2022, from
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-
vaccines/mrna.html
● Li M, Wang H, Tian L, Pang Z, Yang Q, Huang T, Fan J, Song L, Tong Y,
Fan H. COVID-19 vaccine development: milestones, lessons and
prospects. Signal Transduct Target Ther. 2022 May 3;7(1):146. doi:
10.1038/s41392-022-00996-y. PMID: 35504917; PMCID: PMC9062866.