Lecture 1 - patient driven drug development

Question 1

describe The structure of the corona virus and its implications for vaccines

Answer 1

1. key parts of the coronavirus are the RNA and the spike protein.
2. the RNA is surrounded by an envelope which has different roles in the life cycle of the virus. These may include the assembly of new virus and helping new virus to leave the infected cell.
3. the spike protein S are anchored into the vial envelope and form a crown like appearance like the solar corona, hence the name coronavirus. the spike proteins attack to the target cell and allow the virus to enter it
4. the RNA is inside the envelope and acts as a template so that once it is inside the hot cell, the coronavirus can replicate itself and be released int he body
5. The spike protein and the RNA have been used to develop and make different vaccines to protect against SARs-CoV-2

Question 2

how do vaccines work?

Answer 2

SARS-CoV-2is the virus that causes COVID-19. Thespike proteinon the surface of SARS-CoV-2 is an example of anantigen.

Vaccines are the best way to train our immune system to recognize viruses, or pieces of viruses, calledantigens. Our immune system createsantibodiesand other defences to protect us.

Question 3

describe the component viral type of vaccine

Answer 3

Protein Subunit: Contains isolated and purified viral proteins

Virus-like Particles (VLP): Contains viral proteins that mimic the structure of the virus, but no genetic material

DNA-basedandRNA-based: Contains viral genetic material (such as mRNA) which provides the instructions for making viral proteins

Non-Replicated Viral Vector: Contains viral genetic material packaged inside another harmless virus thatcannotcopy itself

Replicating Viral Vector: Contains viral genetic material packaged inside another harmless virus thatcancopy itself

Question 4

describe whole virus type of vaccine

Answer 4

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

Live-Attenuated: Contains copies of the virus that have been weakened (attenuated)

Question 5

what are components of the mRNA vaccine formulations for Pfizer-BioNtech ?

Answer 5

it has mRNA (Nucleoside-modified mRNA encoding the viral spike (S) glycoprotein of SARS-CoV-2

contains:

lipids - 1,2-distearoyl-snglycero-3-phosphocholine (DPSC), cholesterol, An ionisable lipid (ALC-3015; proprietary), A PEGylated lipid

buffer - phosphate buffered saline

and other components such as sucrose

Question 6

what are the components of the mRNA vaccine formulations Moderna

Answer 6

mRNA (Nucleoside-modified mRNA encoding the viral spike (S) glycoprotein of SARS-CoV-2

contains

lipids - 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), Cholesterol, An ionisable lipid (SM-102; proprietary to Moderna), A PEGylated lipid

buffers - Tris buffer, Acetic acid, Sodium Acetate

and other components such as sucrose

Question 7

summarise the manufacturing process for lipid nanoparticles (LNPs) used in mRNA vaccine delivery.

Answer 7

1. The lipids dissolved in an organic solvent (e.g. ethanol) are mixed with the mRNA at pH 4 to 5.
2. At this pH the ionisable lipid is cationic and binds to the mRNA.
3. The pH is then raised to 7.4, resulting in the outside of the LNPs being neutral
4. The particles tend to be around 80 to 100 nm.

Question 8

how does the Oxford Covid-19 Vaccine work?

Answer 8

1. The vaccine is based on a modified chimpanzee adenovirus, which has been altered to be harmless to humans. This modified virus serves as the viral vector for the vaccine.
2. The genetic code of the COVID-19 spike protein, which is found on the surface of the coronavirus, is isolated and inserted into the viral vector. This combination forms the ChAdOx1 COVID-19 vaccine.
3. Once administered, the vaccine enters human cells and uses this genetic code to produce the coronavirus spike protein. This does not cause disease but prompts the immune system to react. The immune response primes the body to recognize and attack the coronavirus if the person is exposed to the actual virus later.

Question 9

descried what happens when the virus enters a cell

Answer 9

After the vaccine is injected into a person’s arm, the adenoviruses bump into cells and latch onto proteins on their surface. The cell engulfs the virus in a bubble and pulls it inside. Once inside, the adenovirus escapes from the bubble and travels to the nucleus,where DNA is s

The adenovirus pushes its DNA into the nucleus. The adenovirus is engineered so it can’t make copies of itself, but the gene for the coronavirus spike protein can be read by the cell and copied into a molecule called messenger RNA, or mRNA.

Question 10

How does the vaccine cause building of spike proteins?

Answer 10

1. The mRNA leaves the nucleus, and the cell’s molecules read its sequence and begin assembling spike proteins.
2. Some of the spike proteins produced by the cell form spikes that migrate to its surface and stick out their tips. The vaccinated cells also break up some of the proteins into fragments, which they present on their surface. These protruding spikes and spike protein fragments can then be recognized by the immune system.
3. The adenovirus also provokes the immune system by switching on the cell’s alarm systems. The cell sends out warning signals to activate immune cells nearby.

Question 11

describe the immune response - spotting the intruder

Answer 11

When a vaccinated cell dies, the debris contains spike proteins and protein fragments that can then be taken up by a type of immune cell called an antigen-presenting cell.

The cell presents fragments of the spike protein on its surface. When other cells called helper T cells detect these fragments, the helper T cells can raise the alarm and help marshal other immune cells to fight the infection.

Question 12

outline how the body generates an immune response to stop the virus after vaccination

Answer 12

Making antibodies:
Other immune cells, called B cells, may bump into the coronavirus spikes on the surface of vaccinated cells, or free-floating spike protein fragments. A few of the B cells may be able to lock onto the spike proteins. If these B cells are then activated by helper T cells, they will start to proliferate and pour out antibodies that target the spike protein.

stopping the virus:
The antibodies can latch onto coronavirus spikes, mark the virus for destruction and prevent infection by blocking the spikes from attaching to other cells.

Killing Infected Cells
The antigen-presenting cells can also activate another type of immune cell called a killer T cell to seek out and destroy any infected cells that display the spike protein fragments on their surfaces.
Remembering the Virus

The immune system also contains special cells called memory B cells and memory T cells that might retain information about the coronavirus for years or even decades.

Question 13

outline the patient invovlebemnt in clinical trials

Answer 13

phase 1 clinical trials assess the initial safety of the vaccine and typically enrol hundreds and thousands of people

phase 2 are larger studies to continue safety assessment and test immunosuppression in health individuals

phase 3 The largest trials providing robust evidence of the vaccine’s safety and efficacy, involving tens of thousands or sometimes over 100,000 volunteers who are randomly assigned to receive either the vaccine or a placebo.

Question 14

what are key factors that inform the UK vaccination policy ?

Answer 14

The Joint Committee on Vaccination and Immunisation (JCVI) advises the UK health departments on immunizations. They assess the availability and suitability of vaccines based on safety and effectiveness, and the need for a vaccination program.

The availability of a suitable vaccine that is safe and effective is crucial.

The SARS-CoV-2 virus, which has caused a significant public health problem with widespread and sustained transmission, affects all age groups and has led to outbreaks in nursing and residential homes, schools, and communities

Question 15

what are the legal requirements for the supply and administration of vaccines?

Answer 15

The regulation of medicines is defined under the Human Medicines Regulations 2012 * All vaccines are classified as Prescription Only Medicines (POMs)

This means that they are subject to legal restrictions and in order to give them, there needs to be an appropriate legal framework in place before they can be supplied and/or administered to eligible people

Additionally, any person who supplies and administers a vaccine must have a legal authority to do so

Question 16

what is the regulatory approval and licensing for vaccines in the UK?

Answer 16

In the UK, vaccine manufacturers apply to the Medicines and Healthcare products Regulatory Agency (MHRA) or the European Medicines Agency (EMA) for a product licence but they may issue a temporary authorisation ahead of the full UK product licence

In exceptional situations, the MHRA may enact Regulation 174, this enables them to temporarily authorise the supply of an unauthorised medicinal product in response to certain identified public health risks, such as the SARS-CoV-2 pandemic

The MHRA assess all of the available safety, quality and efficacy data and consider whether the evidence supports the use of the medicine or vaccine under the legal basis of regulation 174 until it can be licensed (they do not consider cost)

The process involves the same level of scrutiny as the usual licensing process and this exception is only used when strictly necessary to speed up access to a potentially lifesaving intervention

Question 17

what msut the immuniser get before administering vaccination ?

Answer 17

The person giving consent must be appropriately informed.
Consent must be voluntary by the individual without undue pressure or coercion.
The person consenting must have the capacity to make the decision.
the immuniser should be guided by the principles of the Adults with Incapacity (Scotland) Act 2000

Question 18

what information must be provided to the patient when gaining consent?

Answer 18

1. Vaccine to be given and the disease that will be prevented
   2.Benefits/risks of vaccination versus risks of the disease
2. Any new information that has become available since consent to previous doses of this vaccine were given if applicable
3. Any possible vaccine reactions and how to treat these
4. Follow-up/information as to any further doses required
5. How any personal data will be stored and kept (information governance)

Question 19

What should an adult be able to do to be considered to have capacity?

Answer 19

Understand the information that you are giving them about the vaccine and any potential risks from it or from the disease it protects against

Consider the information you have given them and retain it for long enough to make a decision on whether to accept or decline the offer of vaccination

Communicate their decision to you

Question 20

how can we support this process of allwoing an adult capacity for consent?

Answer 20

Using communication tools such as ‘easy read’ leaflets
Speaking with them at their best time of day
Asking someone who the person knows and trusts to speak to them

Question 21

what is patient driven drug development?

Answer 21

patient driven drug development is a collaborative approach with pharmaceutical research into rare diseases and patent advocacy groups. patients participate in drug development through clinical trials and compassionate-use programs. they can also help decide which drugs should receive funding over others. they are experts in the filed with first hand experiences of the condition therefore help develop drug development and evaluation

Question 22

what are the advantages of patient driven development?

Answer 22

The advantages of patient-driven drug development include a more patient-centric approach to clinical development

Companies that incorporate the patient perspective early in the product design stage are more likely to create treatments that truly meet the needs of patients and deliver the benefits that patients are looking for.