L13 - Trends in vaccinology 1 (Dr Anu Goenka) Flashcards

Question

How have scientists exploited immune system mechanisms in vaccine platforms?

Answer 1

🧪 Different vaccine platforms harness immune responses by delivering live attenuated, inactivated, subunit, or genetic material-based vaccines, each targeting different aspects of immunity.

Answer 2

🐄 The first vaccine was the cowpox vaccine, developed in 1798. It used the cowpox virus to inoculate individuals against smallpox.

Answer 3

🦠 Live attenuated vaccines contain weakened forms of the pathogen.

Answer 4

🔬We began engineering them in 1881, with vaccines for Anthrax, Measles, BCG (Tuberculosis), and Influenza (LAIV).

Answer 5

☠️ Scientists found that pathogens inactivated with formalin or other methods could still trigger an immune response.

Answer 6

Vaccines (e.g., Typhoid, Polio, Pertussis) were developed by 1896, but they often gave less durable protection than live vaccines.

Answer 7

🧪 Some bacteria cause disease primarily through toxins rather than the pathogen itself (e.g., Diphtheria, Tetanus). Vaccinating against the toxin rather than the whole organism prevents disease. These vaccines were developed in 1923.

Answer 8

🔬 Subunit vaccines contain specific proteins from a pathogen rather than the whole organism.

Answer 9

🧪 These were introduced in 1970 for Anthrax, Pertussis, and Hepatitis B (HepB).

Answer 10

🎭Virus-like particles mimic a virus without containing genetic material, making them excellent at stimulating the immune system e.g. HPV vaccine (1986)

Answer 11

🛡️ Encapsulated bacteria (e.g., Pneumococcus, H. influenzae type B) have a waxy polysaccharide coat that is not very immunogenic, especially in children. Conjugating it to a protein makes the vaccine much more effective by triggering T-dependent antibody production.

Answer 12

🔍 Reverse vaccinology involves sequencing a pathogen’s genome to identify common, conserved antigens for vaccine development. MnB required this approach because its polysaccharide coat cross-reacted with human CNS tissues, making whole-cell vaccines unsafe.

Answer 13

🏃‍♂️ mRNA vaccines are rapidly developed because they only require the genetic code of a pathogen (e.g., SARS-CoV-2 vaccine in 2020 or Ebola). However, they are highly reactogenic (sore arms!) and have uncertain durability.

Answer 14

⚖️ No! Vaccines are part of a toolkit, and different technologies suit different needs: - mRNA vaccines are great for outbreaks but may not provide long-term protection. - Conjugate vaccines give durable paediatric, long-lived immunity / protection - Reverse vaccinology is useful when the immunodominant antigen is unknown. - Live attenuated vaccines provide indirect effects (e.g., herd immunity).

Answer 15

🌍 Indirect effects refer to herd immunity and broader immune system benefits beyond individual protection.

Answer 16

🤰 Maternal vaccines (pertussis, influenza, RSV) protect newborns by passing antibodies through the placenta, providing early immunity before infants can be vaccinated.

Answer 17

👶 Infant vaccines target pathogens that cause severe infections in newborns, including invasive bacterial infections and diarrhoea, which exploit the infant immune system.

Answer 18

🎒 Childhood vaccines boost immunity from early doses and provide protection against additional diseases, especially when maternal antibody levels wane after six months.

Answer 19

🛡️ Maternal IgG antibodies cross the placenta in the second trimester, providing passive immunity. This protection wanes by six months, leading to increased viral infections in infants.

Answer 20

They protect from cervical cancers and meningitis as well as boosting immunity from previous vaccination

Answer 21

🏥 Indirect effects of vaccination occur when a vaccinated individual is less likely to transmit an infection, providing protection to unvaccinated individuals in the population. This is the basis of herd immunity.

Answer 22

👩‍🍼 Pregnant women receive pertussis, influenza, and RSV vaccines to provide passive immunity to their babies. These vaccines allow the transfer of maternal antibodies across the placenta and through breast milk, protecting infants from infections before their own immune system matures.

Answer 23

🤰 During the second trimester, IgG antibodies are actively transported across the placenta to the baby. These antibodies protect the newborn for about six months, after which they begin to wane, making the infant more susceptible to infections.

Answer 24

🍼 Breast milk contains high amounts of secretory IgA (sIgA), which protects mucosal surfaces from pathogens. This is particularly important for preventing gastrointestinal infections in infants.

Answer 25

🌍 Vaccines don’t just protect the individual who receives them—they also reduce disease transmission within the community.

Answer 26

This indirect protection is known as herd immunity, and it helps protect people who: ❌ Cannot be vaccinated due to medical conditions 🚼 Are too young to be vaccinated 💉 Did not mount a strong immune response

Answer 27

If no one is vaccinated, the disease spreads freely among susceptible individuals, leading to high infection rates (R0 number)

Answer 28

🔄 The disease still spreads, but at a reduced rate. Vaccinated individuals are protected, but unvaccinated people remain at risk and can still transmit the disease.

Answer 29

🚧 The disease cannot spread effectively because most people are immune. This protects even those who aren’t vaccinated.

Answer 30

🤝 Most human-to-human transmitted diseases, like measles, polio, and meningococcal infections, rely on herd immunity. However, tetanus does not, because it is not transmitted between people—it comes from environmental exposure (e.g., soil contamination).

Answer 31

📉 The MenC conjugate vaccine caused a rapid decline in meningococcal C cases, particularly in under 20s, who were the main carriers and transmitters of the bacteria.

Answer 32

🦠 Over 20s were protected by herd immunity. Since younger people stopped carrying MenC, older adults were no longer exposed to the bacteria, reducing their risk of infection.

Answer 33

🌍 The vaccine was so effective at reducing transmission that MenC may have disappeared from circulation, meaning it may no longer exists in the population’s oropharynx.

Answer 34

❌ Many people think "I get vaccinated, so I’m protected" is the full story. ✅ In reality, "I get vaccinated, so I’m less likely to transmit the infection" is just as important! Vaccination helps both individuals and entire populations.

Answer 35

👶 Infants need multiple doses because their immune system is still developing and tends to be more tolerant rather than reactive. The repeated doses act as a "kick-start" to train the immune system.

Answer 36

🤷‍♂️ We don’t know for sure if two doses would be sufficient, but one dose is probably not enough. The multiple doses ensure a stronger and longer-lasting immune response.

Answer 37

🦠 Maternal antibodies passed through the placenta neutralise the vaccine if given too early, making it less effective. These antibodies wane gradually, not all at once. By 12 months, most maternal antibodies have decreased enough for the vaccine to work properly.

Answer 38

🌍 In regions with low vaccine coverage and high measles transmission (e.g., Sub-Saharan Africa), the risk of severe measles infection outweighs the limited durability of an early vaccine. These countries vaccinate at 7-9 months to provide some protection, even if it doesn’t last as long.

Answer 39

🏥 The vaccine eliminated MenC carriage in young people, meaning infants are now protected by herd immunity. Because fewer people carry MenC in their throat, infants are less likely to be exposed, so early doses are no longer necessary.

Answer 40

📅 Originally, MenC was given at 2, 4, and 12 months. Now, the 2- and 4-month doses have been removed, leaving just the 12-month booster.

Answer 41

🔢 The R₀ (basic reproduction number) represents how many people, on average, one infected individual will pass the disease to in a completely susceptible population.

Answer 42

🤒 Measles is one of the most infectious diseases, with a very high R₀ value. It is often considered the most clinically important infectious disease due to its ability to spread rapidly.

Answer 43

🌍 Since 2009, measles cases have regularly increased across Europe, leading to frequent epidemics due to insufficient vaccine coverage.

Answer 44

🇬🇧 The UK is no longer included in EU data because it left the European Union, but if it were included, it would likely show moderate measles incidence.

Answer 45

🚸 Unvaccinated children make up the majority of severe measles cases. While vaccinated individuals can still get measles, they usually experience a milder, attenuated form of the disease.

Answer 46

📊 It shows the percentage of EU countries with >95% vaccine coverage for both measles-containing vaccines (MCV1 & MCV2). The data suggests that only 78-80% of EU countries achieve this target, which is too low to maintain herd immunity.

Answer 47

📉 There is a downward trend, meaning fewer countries are reaching the 95% vaccination threshold, increasing the risk of outbreaks.

Answer 48

1️⃣ Catch-up mass vaccination campaigns to improve coverage. 2️⃣ Targeted healthcare for migrant communities, as they often come from countries with low vaccine coverage. 3️⃣ Combating MMR vaccine misinformation, though this is challenging and controversial.

Answer 49

🏥 Migrants often come from countries with broken healthcare systems, leading to low vaccination rates and higher measles susceptibility.

Answer 50

💭 Plato believed in ideal forms, where the perfect version of anything exists in the mind. Applying this to vaccines, we imagine an ideal vaccine with perfect characteristics that we strive to create in reality.

Answer 51

🏆 The perfect vaccine should be: ✅ Durable – Provides long-lasting immunity / protection ✅ predictable on-target effects ✅ tolerable ✅ Minimal side effects – Safe with low risk of adverse effects ✅ Prevents transmission – Stops the disease from spreading ✅ Has indirect effects – Offers wider community protection ✅ Non-invasive – Easy to administer (e.g., needle-free) and tolerable ✅ Affordable – Relatively cheap for global accessibility and manufacturing ✅ Targets a clinically important disease – Prioritizes serious threats ✅ Predictable on-target effects – Works consistently against the pathogen ✅ establishes correlates of protection ✅ thermostable

Answer 52

📊 Resources must be prioritized for high-burden diseases first. 🔹 Example: 30 years ago, it made more sense to focus on pneumococcus and meningococcus vaccines rather than Chikungunya, which was a lower-priority threat at the time.

Answer 53

🌍 Some vaccines, particularly live vaccines, are linked to a reduction in all-cause mortality, meaning they may boost overall immune function beyond just their target disease.

Answer 54

🛡️ Trained innate immunity suggests that some vaccines can prime the innate immune system to fight a broader range of pathogens, beyond what they were designed for.

Answer 55

🎯 Vaccines should have predictable effects to ensure safety, efficacy, and public trust

Answer 56

❄️ Some vaccines (e.g., mRNA COVID-19 vaccines) require ultra-cold storage (-70 to -80°C), making global distribution difficult, especially in low-resource settings.

Answer 57

🧪 A correlate of protection is a measurable immune response (e.g., antibody levels) that indicates vaccine effectiveness. It’s essential for evaluating new vaccines and guiding booster dose strategies.

Answer 58

🔬 Scientists study: 1️⃣ Pathogen transmission – How the disease spreads 2️⃣ Immune responses – The roles of B cells (BSR) and T cells (TCR) 3️⃣ Protective antibodies – Identifying which antibodies are effective 4️⃣ Key antigens – Determining which microbial proteins trigger immunity 5️⃣ Vaccine platforms – Choosing the best delivery method for the disease

Answer 59

⏳ Decades! A successful vaccine can take 20–40 years, requiring thousands of PhDs and postdocs working on different aspects.

Answer 60

🏭 Good Manufacturing Practice (GMP) ensures vaccines are made under strict international quality and safety standards.

Answer 61

1️⃣ Clinical Research – Understanding the disease, immune responses, and transmission. 2️⃣ Microbe Identification – Determining the target pathogen. 3️⃣ Correlate of Protection – Identifying immune markers that indicate protection. 4️⃣ Antigen Selection – Choosing which part of the pathogen will trigger immunity. 5️⃣ Delivery Platform – Deciding the best method to administer the vaccine (e.g., mRNA, viral vector, protein subunit). 6️⃣ Candidate Vaccine – Developing a prototype vaccine for testing. 7️⃣ Manufacture – Producing the vaccine under Good Manufacturing Practices (GMP). 8️⃣ Safety & Immunogenicity Testing – Evaluating the vaccine in animal models (e.g., mice). 9️⃣ Phase 1 Clinical Trials – Small human trials to assess safety and immune response. 🔟 Phase 2 Clinical Trials – Larger trials to refine dosage and effectiveness. 1️⃣1️⃣ Phase 3 Clinical Trials – Large-scale trials to confirm efficacy and monitor rare side effects. 1️⃣2️⃣ Licensure – Regulatory approval for public use.

Answer 62

👩‍⚕️ Clinical testing has three main phases: 🔹 Phase 1 – Small group, tests safety & immune response 🔹 Phase 2 – Larger group, refines dose & effectiveness 🔹 Phase 3 – Thousands of participants, confirms real-world efficacy

Answer 63

🐭 First, the vaccine is tested in animals (e.g., mice) for safety and to measure immune responses.

Answer 64

👩‍⚕️ Clinical testing has three main phases: 🔹 Phase 1 – Small group, tests safety & immune response 🔹 Phase 2 – Larger group, refines dose & effectiveness 🔹 Phase 3 – Thousands of participants, confirms real-world efficacy

Answer 65

✅ If the vaccine passes all trials, it receives a license for public use.

Answer 66

💀 Most candidate vaccines never make it through trials. The 'Valley of Death' is where thousands of vaccine projects fail due to: ❌ Ineffectiveness ❌ Safety concerns ❌ Funding shortages ❌ Manufacturing challenges

Answer 67

🪦 Scientists abandon failed candidates, sometimes revisiting them years later with new technology or insights ( or crying over them)

Answer 68

1️⃣ Phase 3 Clinical Trials: Compare vaccinated and placebo groups to measure disease occurrence. Expensive and require high infection rates. 2️⃣ Immunocorrelates (Correlates of Protection): Biological measurements (often in blood) that correlate with protection. Typically identified from vaccine failures in Phase 3 trials (those vaccinated but still infected).

Answer 69

🔹 Human Sampling Challenges – Blood is the most accessible sample, but it has limitations as most immune responses to disease involve other parts of the body 🔹 Reproducibility & Assay Feasibility – Standardization is difficult across labs worldwide.

Answer 70

🧪 Binding Antibodies – Measured via ELISA (e.g., Streptococcus pneumoniae). 🛑 Neutralization Assays – Test virus-blocking ability (e.g., RSV). 🦠 Bactericidal Assays – Serial dilution tests to see antibody effectiveness in killing bacteria (e.g., Neisseria meningitidis). 🦠 Haemagglutinin Assays – Used for influenza vaccines.

Answer 71

🚀 Laboratory Advances – Standardization and improved communication across research labs. 🤖 AI & Systems Immunology – Using complex regression models to identify new correlates of protection. 🧫 Human Challenge Models – Deliberate infection with a low-dose or weakened pathogen to study immune responses.

Answer 72

🦠 Malaria poses unique vaccine challenges due to: - The parasite’s complex life cycle - Immune evasion, making traditional vaccine strategies less effective - Frequent antigenic variation, where the parasite’s proteins change throughout its life cycle

Answer 73

🔬 The circumsporozoite protein was chosen as the vaccine target.

Answer 74

- It was displayed on a virus-like particle (VLP) to trigger an immune response - Conjugated to a Hepatitis B antigen to enhance immunogenicity

Answer 75

💉 The first malaria vaccine (2015) had 32% efficacy against severe malaria with rapid waning immunity. Despite its low efficacy, WHO recommended it due to lack of better options and the urgent need for a solution

Answer 76

🏆 by optomising antigen expression : Higher antigen density on the VLP A yeast expression system was used A new adjuvant (Matrix-M) improved immune response Result: 70% efficacy, durable for at least two years

Answer 77

🌍 it is more effective with 70% effiacy, it is cheaper to produce, easier to manufacture and more thermostable making distribution easier in hot climates

Answer 78

🏭 The main challenge is global manufacturing capacity: Most vaccines are produced in India, which does not have malaria Requires large-scale bioreactors and low-cost labor Cost and delivery logistics are also challenges but can be managed

Answer 79

🏭 due to its large-scale manufacturing capacity, lower labor costs, and advanced biotechnology infrastructure. Despite India not having falciparum malaria, its bioreactors in Bangalore can produce vaccines efficiently and at a lower cost. This is a strong example of globalism, where production occurs in regions best suited for mass manufacturing rather than where the disease is most prevalent.

Answer 80

🦠 Respiratory Syncytial Virus (RSV) causes severe respiratory disease, especially in babies and the elderly. It is a major cause of hospitalization and complications in these vulnerable groups.

Answer 81

😷 The vaccine generated antibodies against the Post-F conformation of the RSV fusion protein. These antibodies helped the virus enter cells instead of blocking it, leading to more severe disease.

Answer 82

🔬 Pre-F is the stable form of the RSV fusion protein before the virus attaches to a cell. Post-F is the form after attachment. Vaccines must target Pre-F because Post-F antibodies can worsen infection.

Answer 83

🏆 They stabilized the Pre-F protein through biochemical modifications to prevent it from shifting into Post-F. This ensured that vaccines generated the right immune response (protective antibodies) without increasing disease severity.

Answer 84

⏳ Scientists needed decades to discover that antibodies against Post-F did not protect against RSV and instead enhanced viral entry into cells, making the disease worse.

Answer 85

💉 Different RSV vaccines are used for different groups: Babies → Monoclonal antibody vaccines Elderly & pregnant individuals → Protein subunit vaccines Live attenuated and mRNA vaccines are still in trials.

Answer 86

🇬🇧 The UK vaccinates pregnant individuals to pass RSV immunity to babies. Most other countries give monoclonal antibody vaccines directly to infants instead.

Answer 87

🍼 Monoclonal antibodies provide immediate passive immunity by directly neutralizing the RSV virus. This protects babies who are too young to mount their own strong immune response.

Answer 88

🤰 The vaccine stimulates the mother's immune system to produce protective antibodies, which are passed to the baby through the placenta, giving newborns early immunity.

Answer 89

🏥 The protein subunit vaccine is safer because it only contains a stabilized Pre-F protein, triggering a strong immune response without the risk of disease enhancement.

Answer 90

🔬 Live attenuated RSV vaccines are being tested, similar to nasal spray flu vaccines. mRNA RSV vaccines are also in trials, aiming to use the same technology as COVID-19 vaccines.

Answer 91

🎉 RSV vaccine development represents a breakthrough in understanding viral protein structures and has led to multiple new vaccine approaches that could improve future vaccine design.

Answer 92

🇬🇧 The UK is one of the only countries to choose maternal RSV vaccination, where pregnant individuals are vaccinated to pass immunity to their babies. Most other countries use monoclonal antibody vaccines for infants instead. The UK also vaccinates both the elderly and pregnant individuals against RSV.

Answer 93

💉 The route of delivery affects the magnitude, quality, and location of the immune response. Most vaccines are given intramuscularly (IM) or intradermally (ID), but mucosal vaccines can provide better protection at the site of infection.

Answer 94

🦠 Mucosal immunity plays a key role in blocking infections at the point of entry, particularly for respiratory diseases. It can reduce transmission better than systemic immunity from injected vaccines.

Answer 95

🤧 Mucosal vaccines, like the Live Attenuated Influenza Vaccine (LAIV), trigger a strong local immune response in the respiratory tract, which helps block transmission of respiratory viruses more effectively than injected vaccines.

Answer 96

🏫 Children are major spreaders of flu, especially to their elderly grandparents. A nasal spray vaccine was needed to provide non-invasive, transmission-blocking immunity to protect both children and older adults.

Answer 97

🌬️ LAIV (Live Attenuated Influenza Vaccine) is a nasal spray that contains weakened forms of the flu virus. It is easy to administer and provides mucosal immunity, reducing flu transmission.

Answer 98

🇬🇧 The UK started rolling out LAIV in 2013 for 2- and 3-year-olds. Over time, the program expanded to school-age children, with 5- to 7-year-olds added by 2015-16 to increase protection.

Answer 99

🌬️ LAIV is delivered directly into the nose, where flu infections typically start. This allows the body to build a strong mucosal immune response, which helps block infection at the entry site and reduce transmission.

Answer 100

⚖️ The inactivated flu vaccine does not strongly block transmission, meaning it wouldn’t effectively protect elderly family members. Since LAIV is non-invasive and effective at reducing transmission, it is the preferred option for children.

Answer 101

🦠 The original trivalent LAIV contained: A(H1N1) A(H3N2) One influenza B strain From 2014 onwards, a quadrivalent LAIV was introduced, adding a second influenza B strain for broader protection.

Answer 102

🔄 LAIV is a seasonal vaccine, meaning it is reformulated every year to match the most prevalent flu strains circulating in the population.

Answer 103

👦 LAIV is licensed for children aged 2 to 18 years in the UK. The rollout initially started with younger children and was later expanded to include older age groups in school-based programs.

Answer 104

The UK introduced LAIV in phases: - 2013 – Vaccinated 2- and 3-year-olds, with school pilot programs. - 2014 – Added 4-year-olds and expanded school pilots. - 2015-16 – Included 5- to 7-year-olds to increase coverage.

Answer 105

👵 The elderly are at higher risk of severe flu complications. Since children are the main spreaders, vaccinating them with LAIV helps reduce "grandparenticide"—the unintentional transmission of flu from grandchildren to grandparents.

Answer 106

🤒 Young children are generally more infectious for most viruses, as their immune systems are still developing and may not effectively contain the virus, making them more likely to spread infections, particularly in close-contact settings like schools.

Answer 107

Vaccines often have indirect effects, meaning they can help protect not only those who are vaccinated but also others in the community by reducing transmission. This is important for vulnerable groups, like the elderly, who may not receive direct protection.

Answer 108

📅 Vaccination schedules are adapted based on the epidemiology of diseases. Doses may be reduced or adjusted to save money, reduce the number of injections, and better fit the needs of the population while maintaining effective immunity.

Answer 109

🤰 The UK chose maternal RSV vaccination because it provides passive immunity to infants, starting at birth, and offers protection for longer durations. This allows for early protection while avoiding the high costs and logistical challenges of administering monoclonal antibodies.

Answer 110

💉 Monoclonal antibodies provide immediate protection right after birth, typically within the first seven days, while maternal vaccines offer protection that starts later but can last longer. Countries focused on short-term protection for infants chose monoclonal antibodies.

Answer 111

⏳ The half-life of monoclonal antibodies was engineered to be longer, offering protection for 6-12 months, similar to naturally acquired transplacental antibodies. This ensures longer protection for infants compared to previous monoclonal antibody treatments, which lasted about one month.

Answer 112

🌍 Maternal vaccination not only protects the infant but also offers benefits like cost-effectiveness and simplified delivery, as it reduces the need for multiple appointments. Additionally, combining vaccines for different diseases (like flu and RSV) can save resources and improve healthcare efficiency.

Answer 113

💸 Monoclonal antibodies are very expensive to produce, and using them extensively for RSV could divert funds from other critical vaccines. In contrast, maternal vaccination offers a more cost-effective solution in the long run, though both approaches have their place depending on the situation.

Answer 114

🌐 Resource allocation is a constant challenge in global health. Spending on expensive vaccines like monoclonal antibodies means less funding for other vaccines (e.g., chickenpox). Vaccination strategies often need to balance cost with the greatest public health impact.

Answer 115

🌍 The UK’s maternal RSV vaccination strategy is being closely watched by the global community. As more data is collected, the UK could serve as a model for other countries considering maternal vaccines as a way to protect infants from RSV.

Answer 116

🧑‍🤝‍🧑 Cost, efficacy, duration of protection, and delivery are all critical factors in deciding between monoclonal antibodies and maternal vaccination. Monoclonal antibodies offer short-term protection, while maternal vaccination provides longer-lasting immunity at a lower cost.

Answer 117

🌐 Emerging viruses, like SARS-CoV-2, benefit from accelerated development due to advanced vaccine platforms (e.g., mRNA) and global collaboration. While typical vaccines take decades to develop, the urgent need for SARS-CoV-2 vaccines pushed timelines to months ( China sent out the full sequence which sped up)

L13 - Trends in vaccinology 1 (Dr Anu Goenka) Flashcards

1. Describe the key concepts in vaccinology 2. Understand and evaluate the important milestones of vaccinology • Technological advancements • Types of vaccine • Current schedule (UK) 3. Describe the benefits and limitations associated with different vaccine types/strategies (141 cards)