Republic of the Philippines

Region I
SDO 1 Pangasinan I
LYCEUM NORTHWESTERN UNIVERSITY
Dagupan City, Pangasinan
Graduate Studies in Education

Covid-19 vaccine from Pfizer and

BioNTech shows positive results

In partial requirement
for
Special Topics for Science Teachers

Submitted to:

DR. ESMIE T. AGAPALO

Submitted by:

GABRIELA N. FERNANDEZ

July 04, 2020

Science 10 (Third Quarter)
Heredity: Inheritance and Variation
Learning Competencies and Objectives:
1. Explain how protein is made using information from DNA.
a. Identify the role of DNA and RNA in protein synthesis.
b. Relate DNA replication to its complementary structure.
c. Trace the process of replication, transcription and translation.
d. Describe the steps in protein synthesis.
2. Explain how mutations may cause changes in the structure and function of
protein.
a. Compare the different types of mutations and their possible results.

HEALTH AND SCIENCE

Covid-19 vaccine from Pfizer and BioNTech shows positive results
PUBLISHED WED, JUL 1 2020 8:59 AM EDT / UPDATED WED, JUL 1 2020
9:37 AM EDT

An experimental Covid-19 vaccine being developed by the drug giant Pfizer and
the biotech firm BioNTech spurred immune responses in healthy patients, but
also caused fever and other side effects, especially at higher doses.

The first clinical data on the vaccine were disclosed Wednesday in a paper
released on MedRXiv, a preprint server, meaning it has not yet been peer-
reviewed or published in a journal.

The Pfizer study randomly assigned 45 patients to get one of three doses of the
vaccine or placebo. Twelve receive a 10-microgram dose, 12 a 30 μg dose, 12 a
100 μg dose, and nine a placebo. The 100 μg dose caused fevers in half of
patients; a second dose was not given at that level.

Following a second injection three weeks later of the other doses, 8.3% of the
participants in the 10 μg group and 75% of those in the 30 μg group developed
fevers. More than 50% of the patients who received one of those doses reported
some kind of adverse event, including fever and sleep disturbances. None of
these side effects was deemed serious, meaning they did not result in
hospitalization or disability and were not life-threatening.

The vaccine generated antibodies against SARS-CoV-2, the virus that causes
Covid-19, and some of these antibodies were neutralizing, meaning that they
appear to prevent the virus from functioning. Levels of neutralizing antibodies
were 1.8- to 2.8-times the level of that in the recovered patients.

It’s not certain that higher antibody levels will lead to immunity to the virus. To
prove that, Pfizer will need to conduct large studies that aim to prove that people
who have received the vaccine are at least 50% less likely to become infected.
Those studies are expected to begin this summer, mostly in the United States.
Pfizer is testing four different versions of the vaccine, but only one will advance to
larger studies.

The current study did not include pregnant women, and no other information on
the ethnic diversity of participants was noted, although the paper does say that
future studies will need to include a more diverse group.

The second dose, a booster shot, was required for immunity. The patients who
received the single 100 μg dose had lower antibody levels than those who
received two shots of the lower doses.

Fourteen Covid-19 vaccines are currently in human trials, according to the Milken
Institute, including entrants from Inovio, CanSino, AstraZeneca, and Moderna.
More are expected to start soon, including entrants from Merck, Johnson &
Johnson, and Sanofi. In total, 178 vaccines are in various stages of development.

The Pfizer/BioNTech vaccine, like the Moderna vaccine, is based on a

technology called messenger RNA, which uses a key genetic messenger found
in cells to create protein that the immune system then learns to attack. Moderna
has not yet published data on its vaccine but is expected to do so soon.

RNA vaccines: an introduction

Vaccination is one of the major success stories of modern medicine, greatly

reducing the incidence of infectious diseases such as measles, and eradicating
others, such as smallpox. Conventional vaccine approaches have not been as
effective against rapidly evolving pathogens like influenza or emerging disease
threats such as the Ebola or Zika viruses. RNA based vaccines could have an
impact in these areas due to their shorter manufacturing times and greater
effectiveness. Beyond infectious diseases, RNA vaccines have potential as novel
therapeutic options for major diseases such as cancer.

- Unlike a normal vaccine, RNA vaccines work by introducing an mRNA

sequence (the molecule which tells cells what to build) which is coded for
a disease specific antigen, once produced within the body, the antigen is
recognized by the immune system, preparing it to fight the real thing
- RNA vaccines are faster and cheaper to produce than traditional vaccines,
and a RNA based vaccine is also safer for the patient, as they are not
produced using infectious elements
- Production of RNA vaccines is laboratory based, and the process could be
standardized and scaled, allowing quick responses to large outbreaks and
epidemics
- Most current research is into RNA vaccines for infectious diseases and
cancer, for which there are several early-stage clinical trials, there is also
some early research into the potential of RNA vaccines for allergies
 - There is still a lot of work to be done before mRNA vaccines can become
standard treatments, in the meantime, we need a better understanding of
their potential side effects, and more evidence of their long-term efficacy

What are RNA vaccines and how do they work?

Conventional vaccines usually contain inactivated disease-causing organisms or

proteins made by the pathogen (antigens), which work by mimicking the
infectious agent. They stimulate the body’s immune response, so it is primed to
respond more rapidly and effectively if exposed to the infectious agent in the
future.

RNA vaccines use a different approach that takes advantage of the process that
cells use to make proteins: cells use DNA as the template to make messenger
RNA (mRNA) molecules, which are then translated to build proteins. An RNA
vaccine consists of an mRNA strand that codes for a disease-specific antigen.
Once the mRNA strand in the vaccine is inside the body’s cells, the cells use the
genetic information to produce the antigen. This antigen is then displayed on the
cell surface, where it is recognized by the immune system.

How are RNA vaccines produced and administered?

A major advantage of RNA vaccines is that RNA can be produced in the

laboratory from a DNA template using readily available materials, less
expensively and faster than conventional vaccine production, which can require
the use of chicken eggs or other mammalian cells.

RNA vaccines can be delivered using a number of methods: via needle-syringe

injections or needle-free into the skin; via injection into the blood, muscle, lymph
node or directly into organs; or via a nasal spray. The optimal route for vaccine
delivery is not yet known. The exact manufacturing and delivery process of RNA
vaccines can vary depending on the type.

Types of RNA vaccine

1. Non-replicating mRNA
The simplest type of RNA vaccine, an mRNA strand is packaged
and delivered to the body, where it is taken up by the body’s cells to make
the antigen.

2. In vivo self-replicating mRNA

The pathogen-mRNA strand is packaged with additional RNA
strands that ensure it will be copied once the vaccine is inside a cell. This
means that greater quantities of the antigen are made from a smaller
amount of vaccine, helping to ensure a more robust immune response.

3. In vitro dendritic cell non-replicating mRNA vaccine

 Dendritic cells are immune cells that can present antigens on their
cell surface to other types of immune cells to help stimulate an immune
response. These cells are extracted from the patient’s blood, transfected
with the RNA vaccine, then given back to the patient to stimulate an
immune reaction.

Benefits

Benefits of mRNA vaccines over conventional approaches are:

- Safety: RNA vaccines are not made with pathogen particles or inactivated
pathogen, so are non-infectious. RNA does not integrate itself into the
host genome and the RNA strand in the vaccine is degraded once the
protein is made.
- Efficacy: early clinical trial results indicate that these vaccines generate a
reliable immune response and are well-tolerated by healthy individuals,
with few side effects.
- Production: vaccines can be produced more rapidly in the laboratory in a
process that can be standardized, which improves responsiveness to
emerging outbreaks.

Important challenges

The methods to make mRNA vaccines can be very effective. However, there are
technical challenges to overcome to ensure these vaccines work appropriately:

- Unintended effects: the mRNA strand in the vaccine may elicit an

unintended immune reaction. To minimise this the mRNA vaccine
sequences are designed to mimic those produced by mammalian cells.
- Delivery: delivering the vaccine effectively to cells is challenging since free
RNA in the body is quickly broken down. To help achieve delivery, the
RNA strand is incorporated into a larger molecule to help stabilise it and/or
packaged into particles or liposomes.
- Storage: many RNA vaccines, like conventional vaccines, need to be
frozen or refrigerated. Work is ongoing to reliably produce vaccines that
can be stored outside the cold chain, since these will be much more
suitable for use in countries with limited or no refrigeration facilities.

How could RNA vaccines be used for human health?

The most active areas of research into RNA vaccines are infectious diseases and
cancer where there is research ongoing as well as early-stage clinical trials.
Work into the use of RNA vaccines to treat allergy is still at the early research
stage2.

Infectious diseases
Researchers using conventional approaches have struggled to develop effective
vaccines against a number of pathogens, particularly viruses, that cause both
acute (Influenza, Ebola, Zika) and chronic (HIV-1, herpes simplex virus) infection.
RNA vaccines are being explored as a way to more rapidly and cheaply produce
vaccines for these diseases, particularly in response to emerging outbreaks.
Clinical trials have been carried out or are ongoing on mRNA vaccines for
influenza, cytomegalovirus, HIV-1, rabies and Zika virus.

Case study: A recent study explored the use of programmable self-replicating

RNA vaccines, delivered in a nanoparticle, for a range of infectious diseases
including Ebola virus, H1N1 Influenza and Toxoplasma gondii, which were
effective in mice. These vaccines can be manufactured in approximately one
week and made against a range of diseases, demonstrating potential terms of
swift response to disease outbreaks.

Cancer vaccines

Cancer vaccines are a form of immunotherapy, where the vaccine triggers the
immune system into targeting the cancer. Both dendritic cell vaccines and
ersonalized cancer vaccines, where the RNA sequence in the vaccine is
designed to code for cancer-specific antigens, are being explored. Over 50
clinical trials are listed on clinicaltrials.gov for RNA vaccines in a number of
cancers, including blood cancers, melanoma, glioblastoma (brain cancer) and
prostate cancer.

Case study: Researchers sequenced the genomes of tumours from patients with
melanoma. They made RNAs coding for mutant proteins, specific to the patients’
cancers, that could generate an immune response and made these into patient-
specific vaccines. Eight out of thirteen people vaccinated stayed tumour free up
to two years later4

RNA vaccines – who’s involved?

There are a number of companies and initiatives with an interest in RNA

vaccines including the Merit Consortium, which is a European initiative to
develop cancer vaccines, while UniVax is a research collaboration to develop a
universal influenza vaccine. Companies such as Moderna Therapeutics,
CureVac and BioNTech, are involved in phase I trials of RNA vaccines in cancer
and infectious disease. These companies are also exploring the broader use of
RNA therapeutics for diseases where important proteins are missing or defective
and mRNA treatments could be used to express a functional copy of the protein.

Harnessing RNA vaccines for health – what are the challenges and key
considerations?
 - Research and clinical trials: further research is needed to address
technical hurdles such as vaccine stability and delivery. It is not yet certain
which production method(s) are currently the best. Clinical trial data is
limited – more long-term studies are needed to determine the
effectiveness of RNA vaccines.
- Production: vaccine production is currently small scale and it is not clear if
current methods are capable of epidemic-level vaccine production.
- Resources: the personalised approach for cancer vaccines is time and
resource intensive and work is needed to determine if this approach is
cost-effective.
- Safety: better understanding of vaccine adverse effects is needed – these
can include inflammation or autoimmune reactions.

REFERENCES:

 https://www.cnbc.com/2020/07/01/coronavirus-vaccine-from-pfizer-and-
biontech-shows-positive-results-report-says.html?__source=facebook
%7Cmain&fbclid=IwAR0xDWnlMxMlooVaA2GFixYnWUjthJW_kz0Z6GYo
TBV37pA_zk5YZkFE0-Q
 Pardi N, Hogan MJ, Porter FW, et al. mRNA vaccines - a new era in
vaccinology. Nat Rev Drug Discov. 2018; 17(4): 261-279.
 Weiss R, Scheiblhofer S, Thalhamer, J. Generation and Evaluation of
Prophylactic mRNA Vaccines Against Allergy. Methods Mol Biol. 2017;
1499: 123-139.
 Chahal JS, Kahn OF, Cooper CL, et al. Dendrimer-RNA nanoparticles
generate protective immunity against lethal Ebola, H1N1 influenza, and
Toxoplasma gondii challenges with a single dose. Proc Natl Acad Sci
USA. 2016; 113(29): E4133-42.
 Sahin U, Derhovanessian E, Miller M, et al. Personalized RNA mutanome
vaccines mobilize poly-specific therapeutic immunity against cancer.
Nature. 2017; 547(7662): 222-226.