Coronavirus disease 2019 (COVID-19) is a viral respiratory illness that causes fever, coughing,

and shortness of breath, but many other symptoms can occur. COVID-19 is caused by a highly
infectious virus, and it has spread throughout the world. Most people get mild to moderate illness.
Older adults and people with certain health conditions are at high risk for severe illness and death.

Major progress has been made with the COVID-19 vaccination response, and it is critical to
continue the progress, particularly for those most at risk of disease.

The COVID-19 global health emergency saw the fastest vaccine rollout the world has ever seen.
WHO recommends a simplified single-dose regime for primary immunization for most COVID-
19 vaccines which would improve acceptance and uptake and provide adequate protection at a
time when most people have had at least one prior infection.

Vaccine

A vaccine is a biological preparation that provides active acquired immunity to a particular

infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied
and verified. A vaccine typically contains an agent that resembles a disease-causing
microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one
of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a
threat, destroy it, and recognize further and destroy any of the microorganisms associated with that
agent that it may encounter in the future.

Vaccine type

There are many different types of vaccines, each working in a slightly different way to expose the
body to a weakened or inactive form of a virus or bacteria. This helps the body develop immunity

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to the disease without causing the illness itself. There are some of the most common types of
vaccines:

Inactivated vaccines: These vaccines contain viruses or bacteria that have been killed. The killed
germs cannot reproduce, but they can still be recognized by the immune system. This triggers the
immune system to develop immunity to the disease. Examples of inactivated vaccines include the
influenza vaccine, the polio vaccine, and the hepatitis A vaccine.

Subunit vaccines: These vaccines contain only a specific part of a virus or bacterium, such as a
protein or sugar molecule. The subunit is enough to trigger the immune system to develop
immunity to the disease. Examples of subunit vaccines include the hepatitis B vaccine, the
meningococcal vaccine, and the shingles vaccine.

Toxoid vaccines: These vaccines contain a toxin that has been weakened or inactivated. Toxins
are poisonous substances produced by bacteria. Toxoid vaccines help the body develop immunity
to the effects of the toxin, but not to the bacteria itself. An example of a toxoid vaccine is the
tetanus vaccine.

Messenger RNA (mRNA) vaccines: These are a newer type of vaccine that uses genetic material
called messenger RNA (mRNA) to instruct the body's cells to produce a specific protein. The
protein is then recognized by the immune system, which develops immunity to the disease. The
first COVID-19 vaccines to be approved were mRNA vaccines.

Viral vector vaccines: These vaccines use a modified virus to deliver genetic material from
another virus into the body's cells. The cells then produce a protein from the other virus, which
triggers the immune system to develop immunity. Some COVID-19 vaccines are viral vector
vaccines.

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Vaccine Against Covid-19

COVID-19 vaccines are crucial tools in controlling the spread of SARS-CoV-2, the virus
responsible for COVID-19. Several vaccines have been developed, authorized, and distributed
worldwide, each using different technologies to stimulate an immune response.

History of Covid-19 Vaccine

SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), the virus that causes COVID-
19, was isolated in late 2019.Its genetic sequence was published on 11 January 2020, triggering an
urgent international response to prepare for an outbreak and hasten the development of a preventive
COVID-19 vaccine. Since 2020, vaccine development has been expedited via unprecedented
collaboration in the multinational pharmaceutical industry and between governments. By June
2020, tens of billions of dollars were invested by corporations, governments, international health
organizations, and university research groups to develop dozens of vaccine candidates and prepare
for global vaccination programs to immunize against COVID‑19 infection. According to the
Coalition for Epidemic Preparedness Innovations (CEPI), the geographic distribution of
COVID‑19 vaccine development shows North American entities to have about 40% of the activity,
compared to 30% in Asia and Australia, 26% in Europe, and a few projects in South America and
Africa.

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In February 2020, the World Health Organization (WHO) said it did not expect a vaccine against
SARS‑CoV‑2 to become available in less than 18 months. Virologist Paul Offit commented that,
in hindsight, the development of a safe and effective vaccine within 11 months was a remarkable
feat. The rapidly growing infection rate of COVID‑19 worldwide during 2020 stimulated
international alliances and government efforts to urgently organize resources to make multiple
vaccines on shortened timelines, with four vaccine candidates entering human evaluation in
March.

On 24 June 2020, China approved the CanSino vaccine for limited use in the military and two
inactivated virus vaccines for emergency use in high-risk occupations. On 11 August 2020, Russia
announced the approval of its Sputnik V vaccine for emergency use, though one month later only
small amounts of the vaccine had been distributed for use outside of the phase 3 trial.

The Pfizer–BioNTech partnership submitted an Emergency Use Authorization (EUA) request to

the U.S. Food and Drug Administration (FDA) for the mRNA vaccine BNT162b2 (active
ingredient tozinameran) on 20 November 2020. On 2 December 2020, the United Kingdom's
Medicines and Healthcare products Regulatory Agency (MHRA) gave temporary regulatory
approval for the Pfizer–BioNTech vaccine, becoming the first country to approve the vaccine and
the first country in the Western world to approve the use of any COVID‑19 vaccine. As of 21
December 2020, many countries and the European Union had authorized or approved the Pfizer–
BioNTech COVID‑19 vaccine. Bahrain and the United Arab Emirates granted emergency
marketing authorization for the Sinopharm BIBP vaccine. On 11 December 2020, the FDA granted
an EUA for the Pfizer–BioNTech COVID‑19 vaccine. A week later, they granted an EUA for
mRNA-1273 (active ingredient elasomeran), the Moderna vaccine.

On 31 March 2021, the Russian government announced that they had registered the first
COVID‑19 vaccine for animals. Named Carnivac-Cov, it is an inactivated vaccine for carnivorous
animals, including pets, aimed at preventing mutations that occur during the interspecies
transmission of SARS-CoV-2.

In October 2022, China began administering an oral vaccine developed by CanSino Biologics
using its adenovirus model. Despite the availability of mRNA and viral vector vaccines, worldwide

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vaccine equity has not been achieved. The ongoing development and use of whole inactivated
virus (WIV) and protein-based vaccines has been recommended, especially for use in developing
countries, to dampen further waves of the pandemic.

In November 2021, the full nucleotide sequences of the AstraZeneca and Pfizer/BioNTech
vaccines were released by the UK Medicines and Healthcare products Regulatory Agency in
response to a freedom of information request.

Major Types of COVID-19 Vaccines:

❖ Viral Vector Vaccines

Viral vector vaccines are an innovative approach in the fight against COVID-19, leveraging
modified viruses to deliver genetic instructions from SARS-CoV-2, the virus causing COVID-19.
These vaccines have played a crucial role in the global vaccination effort.

Mechanism of Action

Vector Selection:

A harmless virus is chosen as the vector, commonly adenoviruses, which are modified to be non-
replicating to ensure safety.

Genetic Engineering:

The vector is engineered to carry the gene encoding the SARS-CoV-2 spike protein.

Vaccination Process:

Upon administration, the vector enters human cells and delivers the spike protein gene.

Protein Production:

Human cells use the genetic material to produce the spike protein.

Immune Response:

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The immune system identifies the spike protein as foreign, triggering an immune response
including antibody production and T-cell activation.

Immunological Memory:

This primes the immune system to recognize and combat the actual SARS-CoV-2 virus if exposed
in the future.

Fig: Mechanism of Viral Vector Vaccines

Examples of Viral Vector COVID-19 Vaccines

Oxford-AstraZeneca (AZD1222), Sputnik V

Oxford Astrazeneca Vaccine :

The Oxford-AstraZeneca vaccine development process did involve pre-clinical trials before
progressing to human testing.

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Human adenovirus (Ad26) act as the vector.

Efficacy: Approximately 66% with a single dose.

Notable for its single-dose regimen, facilitating mass vaccination efforts.

Developed by University of Oxford and AstraZeneca.

Sputnik V:

Developed by the Gamaleya Research Institute in Russia.

Uses two different human adenoviruses (Ad26 and Ad5) for the first and second doses.

Efficacy: Around 91.6%, offering robust protection.

Advantages

➢ Strong Immune Response: Induces both humoral (antibody) and cellular (T-cell) immune
responses, providing comprehensive immunity.
➢ Stability: Generally stable at standard refrigerator temperatures, easing storage and
distribution logistics.
➢ Established Technology: Built on platforms used in previous vaccines (e.g., Ebola),
ensuring a reliable safety profile.

Challenges

➢ Preexisting Immunity: Some people may have preexisting immunity to the vector virus,
which can reduce vaccine efficacy.
➢ Complex Manufacturing:
➢ Production requires sophisticated technology and infrastructure, potentially limiting rapid
scale-up.
➢ Vaccine Hesitancy: Public concerns about new technologies can affect uptake rates.

❖ Protein Subunit Vaccines for COVID-19

Protein subunit vaccines are a traditional vaccine approach that utilizes specific pieces of the virus,
such as the spike protein of SARS-CoV-2, to trigger an immune response. These vaccines present

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a focused immune target without using live components of the virus, enhancing safety and
reducing the risk of adverse reactions.

Mechanism of Action

✓ Antigen Selection: The spike protein or a fragment of it is selected as the antigen because
it is crucial for the virus to enter human cells.
✓ Protein Production: The selected protein is produced in the laboratory using recombinant
DNA technology. This often involves inserting the genetic code for the spike protein into
cells that can mass-produce it.
✓ Adjuvant Addition: Adjuvants are added to enhance the immune response. These
substances boost the body’s reaction to the vaccine, ensuring a stronger and longer-lasting
immunity.
✓ Vaccination: The vaccine, consisting of the spike protein and adjuvants, is administered
into the body.
✓ Immune Response: The immune system recognizes the spike protein as foreign, initiating
an immune response that includes the production of antibodies and activation of T-cells.
✓ Memory Formation: The immune system forms memory cells that can quickly recognize
and respond to the actual virus if encountered in the future.

Fig: Protein Subunit Vaccines for COVID-19

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Examples of Protein Subunit COVID-19 Vaccines: Novavax (NVX-CoV2373), ZyCoV-D (Zydus
Cadila), COVOVAX.

Novavax (NVX-CoV2373): Contains a stabilized form of the spike protein, produced using insect
cells.

Adjuvant: Matrix-M to enhance the immune response.

Efficacy: Around 90% against symptomatic COVID-19.

ZyCoV-D (Zydus Cadila): Utilizes a plasmid DNA to produce the spike protein, which is then
used as the vaccine antigen.

Administered using a needle-free system.

Efficacy: Approximately 66% against symptomatic COVID-19.

COVOVAX: Developed by the Serum Institute of India, licensed from Novavax.

Similar composition to Novavax, with recombinant spike protein and Matrix-M adjuvant.

Advantages

➢ Safety: Protein subunit vaccines do not contain live components, minimizing the risk of
infection or severe side effects.
➢ Targeted Immune Response: The immune response is directed specifically against the
spike protein, which is crucial for neutralizing the virus.
➢ Established Technology: Leveraging well-known techniques, reducing the development
time and enhancing trust in their safety profile.

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Challenges

➢ Multiple Doses: Typically require multiple doses to achieve strong immunity, potentially
complicating vaccination campaigns.
➢ Adjuvant Dependency: The need for adjuvants can add complexity to the formulation and
manufacturing process.
➢ Logistics and Cold Chain: Requires a robust cold chain for storage and transportation,
although not as demanding as some mRNA vaccines.

❖ Inactivated or Attenuated Vaccines for COVID-19

Inactivated and attenuated vaccines are traditional vaccine approaches that use whole viruses to
elicit an immune response. Inactivated vaccines contain viruses that have been killed, while
attenuated vaccines use live but weakened viruses. These types of vaccines have a long history of
use in preventing infectious diseases.

Mechanism of Action

1. Inactivated vaccine
➢ Virus Inactivation: SARS-CoV-2 viruses are grown in cell cultures and then killed using
chemicals (e.g., formaldehyde) or heat.
➢ Immune Response: The inactivated virus cannot replicate but still presents antigens,
particularly the spike protein, to the immune system, triggering antibody production and
T-cell responses.
➢ Memory Formation: The immune system creates memory cells that recognize the virus
if encountered in the future.

2. Attenuated Vaccines:
➢ Virus Attenuation: The virus is weakened through repeated culturing or genetic
modification, reducing its ability to cause disease while still being able to replicate.
➢ Immune Response: The attenuated virus mimics a natural infection, provoking a robust
immune response including both antibodies and cellular immunity.

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 ➢ Memory Formation: This also leads to the formation of long-lasting immunological
memory, enabling quick responses to future infections.

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Examples of Inactivated and Attenuated COVID-19 Vaccines Inactivated Vaccines: Sinopharm
(BBIBP-CorV), Sinovac (CoronaVac), Covaxin

Sinopharm (BBIBP-CorV): Developed by China National Pharmaceutical Group (Sinopharm).

Efficacy: Approximately 79% in preventing symptomatic COVID-19.

Storage: Stable at 2-8°C, suitable for standard refrigeration.

Sinovac (CoronaVac): Developed by Sinovac Biotech.

Efficacy: Varies between studies, approximately 50-83%.

Storage: Also stable at 2-8°C.

Covaxin: Developed by Bharat Biotech in India.

Efficacy: Around 78% in clinical trials.

Storage: Stable at 2-8°C.

Attenuated Vaccines: Codagenix/Serum Institute of India:

Uses live attenuated SARS-CoV-2 virus.

Still under development and undergoing clinical trials.

Potential for strong and broad immune responses due to the live attenuated approach.

Advantages

1. Inactivated Vaccines:
➢ Safety:Cannot cause disease since the virus is dead.

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 ➢ Stability:Generally stable at refrigerator temperatures, easing storage and distribution.
➢ Established Technology:Well-understood production processes with a long history of safe
use.

2.Attenuated Vaccines:

➢ Strong Immune Response: Mimic natural infection, often leading to strong and long-lasting
immunity.
➢ Broad Protection: Can stimulate both antibody and cellular immune responses.
➢ Fewer Doses: Often effective with fewer doses due to the strong immune response.

Challenges

Inactivated Vaccines:

➢ Multiple Doses:Often require multiple doses and booster shots for long-lasting immunity.
➢ Weaker Immune Response:May not provoke as strong an immune response compared to
live vaccines.
➢ Adjuvants:Often need adjuvants to enhance the immune response, which can complicate
production.

Attenuated Vaccines:

➢ Safety Concerns:Risk of causing disease in immunocompromised individuals.

➢ Complex Production:More challenging to produce and maintain attenuation consistently.
➢ Storage:May require more stringent storage conditions to maintain viability

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Oxford astrazeneca vaccine

The Oxford-AstraZeneca COVID-19 vaccine, also known as ChAdOx1-S [recombinant] or

Vaxzevria, is a viral vector vaccine developed to prevent infection by the SARS-CoV-2 virus that
causes COVID-19.

❖ Employs a weakened chimpanzee adenovirus (ChAdOx1) as a vector.

❖ This vector carries genetic material encoding the SARS-CoV-2 spike protein into human
cells.
❖ Cells then produce the spike protein, triggering the immune system to recognize and
develop defenses against the virus.

History of Oxford astrazeneca vaccine

Early Development (2016-2020): The University of Oxford's Jenner Institute had experience
developing vaccines for other viruses. With funding from the UK government, research on viral
vector vaccines began in 2016, laying the groundwork for the COVID-19 vaccine.

Rapid Response (2020):Following the emergence of COVID-19, Oxford scientists quickly

adapted their existing research to target the SARS-CoV-2 virus. Partnership with AstraZeneca
ensured large-scale manufacturing and global distribution capabilities.

Clinical Trials (2020-2021): Large-scale clinical trials across multiple countries assessed the
vaccine's safety and effectiveness.bResults showed good efficacy against symptomatic COVID-
19, with a booster shot further enhancing protection.

Approval and Rollout (2020-present): The UK became the first country to approve the vaccine
in December 2020, followed by many others globally.

AstraZeneca's commitment to affordability and wide distribution made the vaccine accessible to
low- and middle-income countries.

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Impact and Ongoing Research (present): Studies suggest the Oxford-AstraZeneca vaccine
saved millions of lives in its first year of rollout. Research continues to evaluate the vaccine's
effectiveness against new variants and explore booster strategies.

Development

• Pre-Clinical Trials: Setting the Stage

Pre-clinical trials are crucial initial steps to assess a vaccine candidate's safety and potential
efficacy before involving humans. These trials typically involve cell cultures and animal models.

The Case of Oxford-AstraZeneca Vaccine:

In the case of the Oxford-AstraZeneca vaccine, pre-clinical studies used cell cultures to evaluate
the vaccine's ability to induce immune responses.

Scientists observed the vaccine successfully triggered the production of antibodies and immune
cells targeting the SARS-CoV-2 spike protein in these cultures.

Animal Models:

More importantly, pre-clinical trials also involved studies in animal models, typically rodents like
mice or rats, and sometimes non-human primates. The Oxford-AstraZeneca vaccine was likely
tested in these animal models to assess:

Safety: Whether the vaccine caused any harmful effects in the animals.

Immunogenicity: The ability of the vaccine to stimulate an immune response against the SARS-
CoV-2 spike protein.

Protection: Whether the vaccine offered some level of protection against the virus in these animals
upon exposure.

Outcomes of Pre-Clinical Trials:

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The specific details of the Oxford-AstraZeneca vaccine's pre-clinical trials haven't been widely
published. However, based on available information:

The vaccine likely demonstrated an acceptable safety profile and the ability to generate an immune
response in animal models.

These positive pre-clinical results paved the way for further evaluation in human clinical trials.

• Oxford astrazeneca vaccine clinical trial

The Oxford-AstraZeneca vaccine went through rigorous clinical trials to assess its safety and
efficacy before widespread use.

Phases of Clinical Trials:

Phase I: This initial phase involved a small group of healthy volunteers (typically 18-50 healthy
adults) to assess the vaccine's safety, dosage, and potential side effects.

Phase II: This phase expanded the study to a few hundred volunteers from diverse backgrounds,
including older adults and people with underlying health conditions.Researchers evaluated the
vaccine's ability to generate an immune response (immunogenicity) and refine the dosage regimen.

Phase III: This large-scale phase involved tens of thousands of volunteers across multiple
countries. Researchers compared the vaccine to a placebo (inactive control) to determine its
effectiveness in preventing COVID-19 and monitored for any serious adverse events.

The Oxford-AstraZeneca Trial Design:

The trials were randomized, double-blind studies. This means participants were randomly assigned
to receive either the vaccine or a placebo, and neither the participants nor the researchers knew
who received which until the study was unblinded.

The trials included diverse populations from various regions to ensure generalizability of the
results to a broader population.

Different dosing schedules were also evaluated to determine the most optimal approach.

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 • Regulatory Approval of the Oxford-AstraZeneca Vaccine:

The Oxford-AstraZeneca vaccine went through a rigorous regulatory process to ensure its safety,
efficacy, and quality before widespread use.

National and International Bodies:

Vaccines are typically approved by national regulatory agencies, although international

organizations like the World Health Organization (WHO) play a crucial role in prequalification
for low- and middle-income countries.

Key Regulatory Bodies:

United Kingdom (UK): The Medicines and Healthcare products Regulatory Agency (MHRA)
was the first to grant approval in December 2020 under a rolling review process. This allowed for
continuous data analysis from ongoing clinical trials, expediting approval without compromising
safety. A full marketing authorization followed in June 2021.

European Medicines Agency (EMA): Granted a Conditional Marketing Authorization (CMA)

in January 2021, allowing for marketing while data collection continued.

World Health Organization (WHO): Granted Emergency Use Listing (EUL) in February 2021,
facilitating access for low- and middle-income countries.

Basis for Approval:

Regulatory decisions rely on data from clinical trials, focusing on:

➢ Safety: Evaluation of potential side effects and associated risks.

➢ Efficacy: Assessment of the vaccine's ability to prevent COVID-19 infection or severe
illness.
➢ Quality: Ensuring the vaccine is pure, potent, and manufactured according to strict
standards.

The Oxford-AstraZeneca Case:

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The initial concerns regarding rare blood clots led to temporary pauses in some countries.
However, regulatory bodies thoroughly investigated these concerns and concluded the benefits of
the vaccine outweigh the risks for most individuals.

Regulatory agencies continue to monitor the vaccine's safety and effectiveness after its rollout
through pharmacovigilance programs.

Global Considerations:

The Oxford-AstraZeneca vaccine received approval from various national and international bodies
due to its positive clinical trial data.

The lower cost of the vaccine compared to some others made it particularly attractive for low- and
middle-income countries, facilitated by WHO prequalification.

• The Manufacturing

Starting Materials:

Virus Seed Stock: Scientists cultivate a highly purified stock of a genetically modified chimpanzee
adenovirus (ChAdOx1) carrying the SARS-CoV-2 spike protein gene.

Host Cell Bank: A specific human cell line is grown and preserved as a master cell bank for
efficient viral vector production.

Large-Scale Production:

Bioreactors: Host cells from the master bank are cultured in large stainless-steel tanks under
optimal conditions.

Viral Infection: The ChAdOx1 vector is introduced to the host cells, turning them into factories
that produce viral vectors with the spike protein.

Cell Harvesting: Cells are lysed to release viral particles containing the spike protein.

Purification:

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Filtration: Filters remove large particles and cell debris.

Chromatography: This technique separates viral particles from other components, ensuring high
purity.

Stringent Quality Control: Rigorous testing confirms the absence of contaminants and verifies the
presence of the spike protein.

Pooling and Concentration: Purified viral fractions are pooled and concentrated.

Final Product Formulation:

Buffering: Purified viral particles are combined with buffers and stabilizers to ensure stability
during storage and transport.

Aseptic Filling: The final product is filled into sterile vials under aseptic conditions.

Quality Control and Release:

Extensive Testing: Each batch undergoes rigorous testing for sterility, potency, and safety.

Regulatory Compliance: The vaccine must meet all regulatory requirements and receive approval
from bodies like the MHRA or EMA before widespread use.

Oxford-AstraZeneca Vaccine: Quality Control in a Nutshell

The Oxford-AstraZeneca vaccine adheres to stringent quality control measures throughout its
production process to ensure safety, purity, and potency.

Rigorous testing happens at each stage of production, not just at the end. Purity and identity of the
virus seed stock and host cell line are verified. Viral growth, cell harvesting, and purification are
monitored for efficiency and potential contamination. Extensive testing ensures.Absence of
microorganisms that could cause infections. Presence of the desired amount of the SARS-CoV-2
spike protein. Absence of harmful contaminants or unexpected byproducts. Testing protocols
comply with regulations set by agencies like MHRA and EMA. These tests ensure the final vaccine

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meets pre-defined safety and efficacy standards. Even after release, regulatory bodies monitor the
vaccine's safety and effectiveness through ongoing surveillance programs.

Novavax (NVX-CoV2373)

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Novavax's NVX-CoV2373 vaccine stands out as a recombinant protein subunit vaccine designed
to combat COVID-19. NVX-CoV2373 is a non-replicating protein subunit vaccine targeting the
SARS-CoV-2 virus, the cause of COVID-19..Unlike mRNA or viral vector vaccines, it doesn't
introduce genetic material into cells. Instead, it delivers purified spike proteins, a crucial
component on the surface of the virus, to the immune system.

➢ Once injected, the immune system recognizes the purified spike proteins as foreign and
triggers an immune response.
➢ This response involves the production of antibodies and immune cells specifically targeted
against the spike protein.
➢ If a person later encounters the actual virus, their immune system is prepared to fight it off
effectively.

Pre-Clinical Trials: Setting the Stage

Novavax (NVX-CoV2373) is a protein subunit vaccine candidate against COVID-19. It was

developed by Novavax, a biotechnology company based in Gaithersburg, Maryland. The vaccine
is made using a recombinant baculovirus vector system to express the SARS-CoV-2 spike protein.
The spike protein is the part of the virus that allows it to enter cells.

➢ Pre-clinical trials are studies that are conducted in animals before a vaccine is tested in
humans. The purpose of pre-clinical trials is to evaluate the safety and efficacy of a vaccine
candidate.
➢ Novavax's NVX-CoV2373 vaccine candidate was evaluated in a number of pre-clinical
trials. These trials included studies in mice, rats, monkeys, and rabbits. The results of these
trials showed that the vaccine candidate was safe and induced a strong immune response.
➢ Based on the results of the pre-clinical trials, Novavax was able to begin clinical trials of
the NVX-CoV2373 vaccine candidate in humans.

Findings from Novavax's pre-clinical trials of NVX-CoV2373:

• The vaccine candidate was safe and well-tolerated in all animal species studied.
• The vaccine candidate induced a strong immune response in all animal species studied.

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 • The immune response induced by the vaccine candidate was protective against SARS-
CoV-2 challenge in mice and monkeys.

Clinical Trials

NVX-CoV2373 COVID-19 Vaccine in Adolescents" provides an in-depth analysis of a clinical

trial evaluating the NVX-CoV2373 vaccine in adolescents aged 12 to 17 years. The study aimed
to assess the safety, immunogenicity, and efficacy of the NVX-CoV2373 COVID-19 vaccine in
adolescents, following its successful evaluation in adults.

➢ Design and Participants: This was a phase 3, randomized, observer-blinded, placebo-

controlled multicenter clinical trial conducted in the US. Participants were enrolled
between April 26 and June 5, 2021. A total of 2247 adolescents were randomized, with
1487 receiving the NVX-CoV2373 vaccine and 745 receiving a placebo.
➢ Interventions: Participants were given two intramuscular injections of either NVX-
CoV2373 or placebo, 21 days apart.
➢ Outcomes Measured: The main outcomes included the serologic noninferiority of
neutralizing antibody responses compared to young adults (aged 18-25 years), protective
efficacy against laboratory-confirmed COVID-19, and the assessment of reactogenicity
and safety.

Results:

➢ The mean age of participants was 13.8 years, with 52.5% being male and 74.4% being
White individuals.
➢ The vaccine demonstrated a neutralizing antibody response in adolescents that was
noninferior to young adults, with a geometric mean titer ratio of 1.5.
➢ The vaccine efficacy against COVID-19 was 79.5%, and 82.0% against the Delta variant
specifically.
➢ Reactogenicity was mostly mild to moderate and transient, with serious adverse events
being rare and evenly distributed between vaccine and placebo groups.

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 • Regulatory: Review and Approval

The NVX-CoV2373 vaccine, also known as Nuvaxovid™, has undergone various regulatory
reviews and received approvals for use in multiple regions.

European Union: The Nuvaxovid™ COVID-19 vaccine received conditional authorization for
use in adolescents aged 12 through 17 on July 5, 2022.

Australia: On July 26, 2022, the vaccine was granted provisional registration for use in
adolescents aged 12 through 17.

New Zealand: Expanded provisional approval for the vaccine in adolescents aged 12 through 17
was granted on August 18, 2022.

Japan: The vaccine received expanded approval for use in adolescents aged 12 through 17 on July
26, 2022.

United States: The U.S. FDA granted emergency use authorization for the Novavax COVID-19
vaccine, adjuvanted, for adolescents aged 12 through 17 on August 19, 2022

The manufacturing of the NVX-CoV2373 COVID-19

➢ Production Facilities: The vaccine is manufactured using facilities in different parts of the
world. This includes production capacities developed by partners such as the Serum
Institute of India, which has been integral in scaling up the production.
➢ Production Process: The vaccine is produced using recombinant nanoparticle technology
to generate antigen derived from the coronavirus spike protein. This process is designed to
ensure high levels of purity and consistency in the vaccine product.
➢ Quality Control: Stringent quality control measures are in place to ensure the safety and
efficacy of the vaccine. These measures are critical in maintaining the vaccine’s high
standards across all production batches.
➢ Global Distribution: The produced vaccine is distributed globally, meeting the demands of
different countries and ensuring widespread availability. This global distribution is
supported by regulatory approvals and partnerships with various international
organizations
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The quality control

➢ Clinical Trials: Extensive clinical trials have been conducted to evaluate the safety,
immunogenicity, and efficacy of the NVX-CoV2373 vaccine. These trials included various
age groups and were carried out in multiple phases to gather comprehensive data.
➢ Adverse Events Monitoring: The monitoring of adverse events is a critical part of the
quality control process. During the clinical trials, adverse events were closely tracked, with
findings indicating that serious adverse events were rare and balanced between the vaccine
and placebo groups. No adverse events led to study discontinuation, highlighting the
vaccine's safety profile.
➢ Regulatory Oversight: Regulatory bodies such as the US Food and Drug Administration
(FDA) have been involved in the approval process of the vaccine. The vaccine met the
threshold of efficacy and safety required for emergency use authorization, which includes
rigorous quality control standards set by these agencies.
➢ Global Manufacturing Standards: The manufacturing process adheres to stringent global
standards to maintain the vaccine's quality across different production batches. This
includes the use of recombinant nanoparticle technology to produce the antigen with high
purity and consistency.

Mechanism of NVX-CoV2373

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 Thank You

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