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
What is the significance of vaccination in public health?
🌍 Vaccination is the most effective public health tool after clean water, preventing 2-3 million infectious disease deaths annually.
What are the two types of immunisation?
🛡️ Immunisation can be active (stimulates immune response, e.g., vaccines) or passive (provides pre-formed antibodies, e.g., monoclonal antibodies).
what is immunisation
💉 Immunization is the process of inducing immunity against a pathogen, usually through vaccination. It protects individuals and communities from infectious diseases.
How does active vaccination work?
🦠 Active vaccination introduces antigens from a pathogen to stimulate an immune response.
What are the different types of active vaccines?
🦠 Active vaccines use different approaches to introduce antigens:
- Live attenuated vaccines (weakened form of the pathogen).
- Inactivated vaccines (killed pathogen).
- Subunit vaccines (specific pathogen components, e.g., proteins or polysaccharides).
- Genetic vaccines (mRNA or DNA encoding pathogen proteins).
How does passive vaccination work?
💉 Passive vaccination provides pre-formed antibodies to an individual, offering immediate but temporary protection. It does not stimulate an immune response.
what is an example of passive vaccination
RSV monoclonal antibody vaccines.
What is an antigen in the context of vaccines?
🔑 An antigen is a molecule or part of a pathogen that triggers an immune response. It is the key component in vaccines that the immune system recognizes and reacts to.
WHat is herd immunity?
👥 Herd immunity occurs when a large percentage of the population is immune (through vaccination or infection), reducing disease spread and protecting those who cannot be vaccinated.
Why do vaccines have an advantage over antibiotics?
🏆 Unlike antibiotics, vaccines rarely face escape mutations in pathogens. Antibiotics lose effectiveness due to bacterial adaptation, whereas vaccines can lead to long-term disease control and even eradication.
how do vaccines differ from antibiotics in disease control?
🏆 Vaccines prevent infections, whereas antibiotics treat infections. Unlike antibiotics, vaccines rarely face resistance because pathogens don’t easily escape immune memory.
What is an example of a disease eradicated by vaccine?
✅ Smallpox was eradicated through vaccination. Other near-eradications include polio and measles, but setbacks have prevented complete elimination.
what are possible reasons for measle resurgence?
🧩 Measles was nearly eradicated but has resurged due to vaccine hesitancy and global disruptions.
What factors influence whether a disease can be eradicated?
🔬 Eradication is possible if a disease:
- Has no animal reservoirs (e.g., smallpox).
- Has an effective and widely available vaccine.
- Requires high population immunity to prevent transmission.
who was Edward Jenner, and what was his contribution to vaccinology?
🏛️ Edward Jenner pioneered vaccination by using cowpox to protect against smallpox. His work laid the foundation for modern immunization.
What is the Temple of vaccination?
⛪ The Temple of Vaccination is where Edward Jenner reportedly administered the first vaccines, marking the birth of modern vaccinology.
What was Edward Jenners first vaccination and who to?
The first boy Edward Jenner vaccinated was James Phipps. In 1796, Jenner inoculated him with material taken from a cowpox sore on a milkmaid’s hand, later exposing him to smallpox to test immunity. James did not develop smallpox, proving Jenner’s theory that cowpox could provide protection. 🎉💉
How are vaccines commonly administered?
💉 Parenteral injection into the muscle (intramuscular). Other methods include subcutaneous, intradermal, and inhaled vaccines.
What happens to vaccine antigens once they are introduced into the body?
🦠 Vaccine antigens are taken up by antigen-presenting cells (APCs), which process and present them to the immune system.
What are the main types of antigen-presenting cells (APCs)?
🔬 Dendritic cells, macrophages, monocytes ( and B cells which can also present antigen).
How do APCs present antigens to the immune system?
🎭 APCs present antigens using MHC molecules:
1️⃣ MHC II → CD4+ T helper cells, which help activate B cells to produce antibodies.
2️⃣ MHC I → CD8+ cytotoxic T cells, which have direct effector functions (e.g., killing infected cells).
What is the role of CD4+ T cells in vaccine-iduced immunity?
🛡️ CD4+ T cells (helper T cells) assist B cells in producing antibodies and help form a long-lived memory immune response with plasma cells and memory B cells.
What is the role of CD8+ T cells in vaccine-induced immunity?
⚔️ CD8+ cytotoxic T cells recognise antigens presented on MHC I molecules and can kill infected cells directly, providing cell-mediated immunity.
How have scientists exploited immune system mechanisms in vaccine platforms?
🧪 Different vaccine platforms harness immune responses by delivering live attenuated, inactivated, subunit, or genetic material-based vaccines, each targeting different aspects of immunity.
What was the first vaccine, and how was it developed?
🐄 The first vaccine was the cowpox vaccine, developed in 1798. It used the cowpox virus to inoculate individuals against smallpox.
What are live attenuated vaccines?
🦠 Live attenuated vaccines contain weakened forms of the pathogen.
When did we start to engineer live attenuated vaccines?
🔬We began engineering them in 1881, with vaccines for Anthrax, Measles, BCG (Tuberculosis), and Influenza (LAIV).
What discovery led to the development of killed whole organism vaccines?
☠️ Scientists found that pathogens inactivated with formalin or other methods could still trigger an immune response.
What are examples of killed whole organism vaccines and what are their draw backs?
Vaccines (e.g., Typhoid, Polio, Pertussis) were developed by 1896, but they often gave less durable protection than live vaccines.
How do toxoid vaccines work, and which diseases do they target
🧪 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.
what are subunit vaccines,
🔬 Subunit vaccines contain specific proteins from a pathogen rather than the whole organism.
When and what for were subunit vaccines introduced?
🧪 These were introduced in 1970 for Anthrax, Pertussis, and Hepatitis B (HepB).
What is the role of virus-like particles in vaccines?
🎭Virus-like particles mimic a virus without containing genetic material, making them excellent at stimulating the immune system e.g. HPV vaccine (1986)
What are protein conjugate vaccines needed for encapsulated bacteria?
🛡️ 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.
What is reverse vaccinology, and why was it needed for the Meningococcal B (MnB) vaccine?
🔍 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.
Why are mRNA vaccines effective for outbreaks?
🏃♂️ 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.
Are newer vaccine technologies always better than older ones
⚖️ 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).
What are indirect effects of vaccine?
🌍 Indirect effects refer to herd immunity and broader immune system benefits beyond individual protection.
Why do we give vaccines to pregnant women
🤰 Maternal vaccines (pertussis, influenza, RSV) protect newborns by passing antibodies through the placenta, providing early immunity before infants can be vaccinated.
Why do we give infant vaccines and what do they target?
👶 Infant vaccines target pathogens that cause severe infections in newborns, including invasive bacterial infections and diarrhoea, which exploit the infant immune system.
What role do childhood vaccines play?
🎒 Childhood vaccines boost immunity from early doses and provide protection against additional diseases, especially when maternal antibody levels wane after six months.
Why don’t newborns get many viral infections in the first few weeks
🛡️ 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.
What role do adolescent vaccines play?
They protect from cervical cancers and meningitis as well as boosting immunity from previous vaccination
What are the key concepts behind indrect effects of vaccination?
🏥 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.
What vaccines are given to pregnant mothers and why?
👩🍼 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.
How are maternal antibodies transferred to the baby?
🤰 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.
What role does breast milk play in passive immunity?
🍼 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.
How do vaccines work at the population level?
🌍 Vaccines don’t just protect the individual who receives them—they also reduce disease transmission within the community.
Who does herd immunity protect (indirect protection)
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
What happens in an unvaccinated popylation
If no one is vaccinated, the disease spreads freely among susceptible individuals, leading to high infection rates (R0 number)
What happens when vaccine coverage is below the herd immunity threshold?
🔄 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.
What happens when vaccine coverage is above the herd immunity threshold
🚧 The disease cannot spread effectively because most people are immune. This protects even those who aren’t vaccinated.
what types of diseases rely on herd immunity?
🤝 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).
What was the impact of intriducing the MenC vaccine in the early 200-s?
📉 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.
Why did meningococcal C cases also decline in over 20s who weren’t vaccinated?
🦠 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.
What unexpected effect did the MenC vaccine have on bacterial circulation
🌍 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.
What is the biggest misconception about how vaccines work?
❌ 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.
Why do infantst recieve three doses of primary immunisation at 2,3, and 4 months?
👶 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.
Would one or two doses be enough to give for primary immunisation?
🤷♂️ 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.
WHy don’t we give the MMR vaccine at 6 months instead of 12?
🦠 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.
Why do some countries give the measles vaccine earlier at 7-9 months?
🌍 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.
Why was MenC vaccination at 2 and 4 months removed from the schedule in the UK?
🏥 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.
What was the previous MenC schedule?
📅 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.
What does the R₀ value represent in infectious diseases?
🔢 The R₀ (basic reproduction number) represents how many people, on average, one infected individual will pass the disease to in a completely susceptible population.
How infectious is measles compared to other diseases?
🤒 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.
What does the epidemiological data show about measles in Europe?
🌍 Since 2009, measles cases have regularly increased across Europe, leading to frequent epidemics due to insufficient vaccine coverage.
Why is there no UK data in the European measles reports?
🇬🇧 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.
WHy do most measles cases occur in unvaccinated children?
🚸 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.
What does the dark green histogram in the lecture represent
📊 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.
What trend is seen in measles vaccination coverage in Europe?
📉 There is a downward trend, meaning fewer countries are reaching the 95% vaccination threshold, increasing the risk of outbreaks.
What are the key stretegies for controlling measles outbreaks?
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.
Why are migrant communities more affected by measles?
🏥 Migrants often come from countries with broken healthcare systems, leading to low vaccination rates and higher measles susceptibility.
How does Plato’s ‘World of Ideas’ relate to the concept of a perfect vaccine?
💭 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.
What are the key attributes of an ideal vaccine
🏆 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
Why is there an “ order of importance” in vaccine development?
📊 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.
What are nonspecific effects of vaccines?
🌍 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.
What is the concept of trained immunity?
🛡️ 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.
Why is predictability important in vaccinology?
🎯 Vaccines should have predictable effects to ensure safety, efficacy, and public trust
Why is thermostability crucial for vaccines?
❄️ 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.
What is a correlate of protection and why is it important?
🧪 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.
WHat are the key research areas in vaccine development?
🔬 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
How long does it typically take to develop a vaccine?
⏳ Decades! A successful vaccine can take 20–40 years, requiring thousands of PhDs and postdocs working on different aspects.
what is GMP and why is it important in vaccine production?
🏭 Good Manufacturing Practice (GMP) ensures vaccines are made under strict international quality and safety standards.
What are the key stages in vaccine development?
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.
What are the phases of human vaccine trials.
👩⚕️ 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
What are the preclinical steps in vaccine development?
🐭 First, the vaccine is tested in animals (e.g., mice) for safety and to measure immune responses.
What are the phases of human vaccine trials?
👩⚕️ 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
What happens after successful clinical trials?
✅ If the vaccine passes all trials, it receives a license for public use.
Why do most vaccines fail?
💀 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
What happens to failed vaccine projects?
🪦 Scientists abandon failed candidates, sometimes revisiting them years later with new technology or insights ( or crying over them)
How do we know a vaccie works?
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).
What are the limitations of using correlates of protection as a marker for vaccine efficacy?
🔹 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.
What are different types of serum / antibody correlates of protection?
🧪 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.
What are future directions in vaccine research?
🚀 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.
Why ahs malaria vaccination been such a major challenge?
🦠 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
What protein was targeted for malaria vaccine development?
🔬 The circumsporozoite protein was chosen as the vaccine target.
How was the circumsoirozite protein used for the malaria vaccine?
- It was displayed on a virus-like particle (VLP) to trigger an immune response
- Conjugated to a Hepatitis B antigen to enhance immunogenicity
What is the efficacy of the first malaria vaccine and why was it accepted
💉 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
How was malaria vaccine efficacy improved?
🏆 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
What are the benefist of the improved malaria vaccine
🌍 it is more effective with 70% effiacy, it is cheaper to produce, easier to manufacture and more thermostable making distribution easier in hot climates
What is the biggest challenge in vaccinating 40 million children per year?
🏭 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
Why is the malaria vaccine primarily manufactured in India?
🏭 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.
What is RSV and who is most at risk?
🦠 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.
Why did the first RSV vaccine from the 1960s make the disease worse?
😷 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.
What is the difference between Pre-F and Post-F conformations in RSV?
🔬 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.
How did scientists solve the RSV vaccine problem?
🏆 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.
WHy did it take 30 years to understand the failure of the first RSV vaccine?
⏳ 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.
What types of RSV vaccines are available for different age groups?
💉 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.
How does the UK’s RSV vaccination strategy differ from other countries?
🇬🇧 The UK vaccinates pregnant individuals to pass RSV immunity to babies. Most other countries give monoclonal antibody vaccines directly to infants instead.
How does the monoclonal antibody RSV vaccine for babies work?
🍼 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.
How does the maternal RSV vaccine protect newborns?
🤰 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.
What are the advantages of protection subunit RSV vaccine?
🏥 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.
What type of RSV vaccines are still in development?
🔬 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.
Why is RSV considered a major milestone in vaccinology?
🎉 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.
How is the UK’s RSV vaccination strategy unique?
🇬🇧 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.
How does the route of vaccine delivery impact the immune response?
💉 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.
Why is mucosal immunity important for vaccine effectiveness?
🦠 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.
What is the main advantage of mucosal vaccines?
🤧 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.
Why was a nasal flu vaccine (LAIV) developed for children?
🏫 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.
What is LAIV and how is it delivered?
🌬️ 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.
How has the UK’s childhood flu vaccination program expanded?
🇬🇧 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.
Why is LAIV considered more effective for reducing flu transmission?
🌬️ 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.
Why is it unethical to give children the inactivated flu vaccine instead of LAIV?
⚖️ 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.
What type of flu strains are included in LAIV?
🦠 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.
How often does the LAIV formulation change?
🔄 LAIV is a seasonal vaccine, meaning it is reformulated every year to match the most prevalent flu strains circulating in the population.
What is the age range for LAIV vaccination in the UK?
👦 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.
How did the UK roll out the childhood flu vaccine program?
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.
Why are elderly individuals a key focus in flu prevention?
👵 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.
Why are young children often more infectious than adults for most viruses?
🤒 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.
What is the importance of the indirect effects of vaccines?
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.
Why do vaccine schedules change over time?
📅 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.
Why was a maternal RSV vaccination chosen in the UK instead of monoclonal antibodies for infants?
🤰 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.
Why did most countries, apart from Argentina, choose monoclonal antibodies for infant RSV protection instead of maternal vaccines?
💉 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.
What is the half-life of monoclonal antibodies, and why is it significant for infant protection?
⏳ 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.
What are the benefits of maternal vaccination beyond protecting the infant?
🌍 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.
Why is the cost of monoclonal antibodies a challenge in RSV vaccination?
💸 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.
How does the cost of vaccines affect global health priorities?
🌐 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.
How will the UK’s maternal RSV vaccination strategy impact global health?
🌍 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.
What factors determine the choice between monoclonal antibodies and maternal vaccination for RSV protection?
🧑🤝🧑 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.
How do vaccines for emerging viruses, like SARS-CoV-2, differ in development timelines?
🌐 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)
