Manipulating the Immune Response Flashcards

Question

What stages help ensure a vaccine is safe and potentially effective? What is their primary goal?

Answer 1

Preclinical testing and safety evaluation Primary goal – Assess the safety, immunogenicity, and potential efficacy of a vaccine candidate using laboratory and animal models This stage helps predict how the vaccine might behave in humans

Answer 2

Methods - In vitro studies – Initial tests are conducted using lab-grown cells to evaluate the vaccine’s ability to induce an immune response and to identify any cytotoxic effects - Animal models – Vaccine candidates are tested in animals, such as mice, rats, or non-human primates, to assess safety and immunogenicity; These studies help determine the appropriate dosage and identify potential side effects - Toxicology Studies – These studies evaluate the potential toxicity of the vaccine, including single and repeat-dose toxicity, reproductive toxicity, and other specific safety concerns Outcomes: - Preclinical testing provides data on the vaccine’s ability to elicit an immune response and its safety profile - Successful preclinical results are necessary to proceed to human clinical trials

Answer 3

Phase I – Involves small group of 20-100 healthy volunteers; Primary goal is to assess safety of the vaccine and determine appropriate dosage Phase II – This phase expands to several hundred participants who have characteristics similar to the target population to further evaluate safety and optimise dosage Phase III – In this phase, the vaccine is tested on thousands of participants to confirm its efficacy and monitor for any rare side effects; This phase provides the critical data needed for regulatory approval

Answer 4

Submission of Data – Vaccine manufacturer submits all data from preclinical and clinical studies to regulatory agencies Regulatory Review – Regulatory experts review the data to ensure the vaccine meets all safety, efficacy, and quality standards; This process includes inspecting the manufacturing facilities to ensure they comply with Good Manufacturing Practices (GMP) Licensure – If the vaccine meets all requirements, it is granted a licence for public use - Post-licensure surveillance (Phase IV) continues to monitor the vaccine's safety and effectiveness in the general population

Answer 5

Antigen Production - Depending on the type of vaccine, antigens are produced using various methods such as cell culture, recombinant DNA technology, or viral vectors e.g. cell culture methods involve growing cells that produce the necessary components for the vaccine e.g. recombinant techniques use genetic engineering to produce specific proteins Formulation - Antigen is combined with other components, such as adjuvants, stabilisers, and preservatives, to enhance the immune response and ensure the vaccine's stability and shelf life Purification - The vaccine components are purified to remove any contaminants and ensure the final product's safety and efficacy Filling and Packaging - The purified vaccine is filled into vials or syringes under sterile conditions and then packaged for distribution Quality Control and Assurance - Throughout the manufacturing process, rigorous quality control measures are implemented to ensure that the vaccine meets all safety, efficacy, and quality standards This includes testing for potency, purity, sterility, and consistency

Answer 6

CpG 1018 - Synthetic oligonucleotide that mimics bacterial DNA, used in the Heplisav-B vaccine for hepatitis B to enhance the immune response Aluminium Salts: - Widely used in vaccines for diseases like diphtheria, tetanus, and hepatitis B They have a long history of safe use but are limited in their ability to stimulate a broad immune response

Answer 7

Good Manufacturing Practices (GMP): - All vaccine manufacturing processes must adhere to GMP standards, which ensure that products are consistently produced and controlled according to quality standards This includes maintaining aseptic conditions, proper documentation, and regular inspections Batch Testing: - Each batch of the vaccine is tested for quality and consistency before it is released for distribution This includes tests for sterility, potency, and absence of contaminants Post-Market Surveillance: - Even after a vaccine is approved and distributed, ongoing monitoring is conducted to detect any adverse effects and ensure continued safety and efficacy

Answer 8

Cold Chain Management: - Most vaccines require refrigerated storage at temperatures between 2°C and 8°C - Some vaccines, like mRNA vaccines, require ultra-cold storage at temperatures as low as -70°C Specialised equipment and protocols are used to maintain these temperatures during transportation and storage Distribution Networks: - Vaccines are distributed through a network of refrigerated trucks, warehouses, and portable iceboxes to ensure they remain within the required temperature range until they reach the point of administration

Answer 9

Rapid response: - Emerging diseases require a swift response to develop and distribute vaccines - Often involves accelerated research and regulatory processes, as seen with the COVID-19 vaccines Unknown pathogens: - New pathogens may have unknown characteristics, making it difficult to identify suitable antigens and develop effective vaccines quickly

Answer 10

Misinformation: - Spread of misinformation about vaccine safety and efficacy can lead to reduced vaccination rates and outbreaks of preventable diseases Public Trust: - Building and maintaining public trust in vaccines is crucial - Transparent communication about the benefits and risks of vaccines, as well as addressing concerns and misconceptions, is essential to combat vaccine hesitancy - Expense, lack of appropriate medical infrastructure, patient compliance - Personal/religious objections - “Fake news”

Answer 11

Distribution Inequities - Disparities in vaccine distribution can leave low- and middle-income countries without adequate access to vaccines, exacerbating health inequalities Global Collaboration - Initiatives like COVAX aim to ensure fair distribution of vaccines worldwide, but logistical, financial, and political challenges remain

Answer 12

mRNA vaccines use messenger RNA to instruct cells to produce a protein that triggers an immune response Mechanism – mRNA vaccines deliver genetic instructions to cells to produce a viral protein, such as the spike protein of the SARS-CoV-2 virus Once the protein is made, the immune system recognises it as foreign and mounts an immune response, including the production of antibodies Advantages – These vaccines can be developed and produced more quickly than traditional vaccines They are also highly adaptable, allowing for rapid updates to address emerging variants Examples – Pfizer-BioNTech and Modern vaccines were the first mRNA vaccines authorised for emergency use and have shown high efficacy in preventing COVID-19

Answer 13

Vector virus is engineered to be harmless and unable to replicate Carries genetic code for an antigen, such as protein from target pathogen Once inside body, cells produce the antigen, eliciting immune response - AstraZeneca/Oxford COVID-19 Vaccine – Uses a chimpanzee adenovirus vector to deliver the spike protein gene of SARS-CoV-2 - Beyond COVID-19, viral vector vaccines are being explored for diseases such as Ebola, HIV, and Zika virus

Answer 14

Types of Nanomaterials – Lipid nanoparticles, polymeric nanoparticles, and inorganic nanoparticles are commonly used Functions: - Stabilisation – Protects the antigen from degradation - Targeted delivery – Enhances delivery to specific cells or tissues - Adjuvant Effect – Enhances the immune response by acting as an adjuvant - Pfizer-BioNTech and Moderna COVID-19 vaccines use lipid nanoparticles to encapsulate and deliver the mRNA into cells

Answer 15

Vaccines tailored to the individual characteristics of a patients disease, particularly in the context of cancer Mechanism – These vaccines are designed based in specific mutations or antigens present in a patients tumour They aim to elicit a strong immune response against these unique antigens Applications – BioNTech and Genentech have been conducting clinical trials for mRNA vaccines targeting various cancers, including melanoma, colorectal and lung cancers These trials involve creating individualised vaccines based on each patients tumour profile Personalised vaccines are also being explored for infectious diseases (e.g. HIV), where individual genetic differences affect disease susceptibility

Answer 16

Disease limited to human - No reinvasion by microbe from animal No long term carrier state - No reinvasion by microbe from human carriers Few unrecognised clinical cases - Good surveillance One or few serotypes - Single vaccine is enough Stable, cheap and effective vaccine and programme - Worldwide programme feasible

Answer 17

Polio – Caused by the poliovirus, polio can lead to paralysis and even death; Disease has been nearly eradicated globally due to widespread vaccination with the inactivated polio vaccine (IPV) and oral polio vaccine (OPV) Human Papillomavirus (HPV) – Group of viruses that can cause genital warts and are linked to several cancers, including cervical cancer; HPV vaccine is recommended for adolescents to prevent infection and associated cancers

Answer 18

Barriers in developing effective vaccines for existing infectious diseases due to: - Complex life-cycle of pathogen - T cell immunity needed - High mutation rates - Many types of pathogen

Answer 19

Malaria – Approximately 249 million cases (2022) and 608,000 deaths (2012) African Region bears a disproportionate burden, accounting for 94% of malaria cases (233 million) and 95% (580,000) of malaria deaths in 2022 Malaria vaccine, R21/Matrix-MTM licensed for use in Ghana 2023, 77% effective in clinical trials (endorsed by WHO)

Answer 20

Approximately 1.3 million people became newly infected with HIV in 2022 In 2022, around 630,000 people died from AIDS-related illnesses worldwide, compared to 1.2 million in 2010 Substantial economic impact of HIV/AIDS No really effective current vaccine Treatment – not cure Treatments consume the majority of household budget, especially in low-income settings without adequate healthcare coverage

Answer 21

Preventing Disease Outbreaks – High vaccination coverage is necessary to maintain herd immunity and prevent the resurgence of vaccine-preventable diseases Protecting Vulnerable Populations – Vaccination protects those who cannot be vaccinated, such as infants and immunocompromised individuals, by reducing the spread of infectious diseases Global Health Security – Vaccination is a key component of global health security, helping to prevent and control infectious disease outbreaks and pandemics