Lecture 37 Flashcards
(31 cards)
1
Q
How are vaccines important?
A
came about 200 years ago and Fundamental role in fighting infectious diseases that cause sickness/death by virus or bacteria and now even some in the works for cancer
2
Q
First vaccine?
A
- King Jenner, cowpox 1798, helped control smallpox all the way until complete elimination, today we use covid vaccine to control the pandemic too but HIV that also pandemic, no vaccine we use antiretrovirals, his body of work resembled a phase III clinical trial in both size and scope
- Small pox was responsible for 300-500 million deaths during the 20th century, 20-60% died and 80% of infected children died
- Last naturally occurring case of small pox was diagnosed on 26 October 1977, 1980 WHO declared the world free of small pox
3
Q
Second major vaccine?
A
- Pasteru rabies vaccine in 1885, took virus from infected rabbit and let it dry which gave an attenuated virus and injected into 9 year old boy post exposure and it worked, now we have cell cultures, don’t use rabbits anymore to get it
- 1980 we got new human diploid cell vaccine which is both effective pre and post exposure, purified inactivated pitman Moore strain of rabies, more safe and effective
- 19th century was important for vaccinology with the germ theory of disease proven launching of mimm, discovery of numerous specific bacterial causes of distinct infectious diseases and viruses discovered at the end of the century
- Pasteur discovered the process of microbial attenuation and its implications for immunization and vaccine development
4
Q
Yellow fever virus vaccine
A
- insect vector transmission
- Causes internal bleeding
- Very fatal and pathogenic, found mostly in tropical areas
- MAx theiler developed the 17D yellow fever vaccine in 1937 => using mice and tissue culture to grow and pass virus to attenuate
- Received the Nobel prize, only Nobel prize for a vaccine virus so far
5
Q
Influenza virus vaccine
A
- 1st inactivated virus
- 1931, virus 1st discover in pigs, swine influenza virus and successfully grew in high titers in embryonated hen eggs but then in 1933 found in humans. This work allows preparation of influenza viruses that could be inactivated for vaccination trial => still used today
- 1940s/1945 US military developed the first approved flu vaccine used in world war II
6
Q
Poliovirus vaccine
A
- polio outbreak in many countries 1940-50 => infection of the spine, trouble breathing needed iron lungs to help breathe, many died since only slightly prolonged life
- Vaccine with virus grown in tissue cultire and then inactivated to get vaccine
- YFV, polio and flu all benefitted from ex vivo virus cultivation
7
Q
Name and explain three vaccines with innovative way of making vaccines
A
- Hep B (1981) RECOMBINANT subunit vaccine, not whole virus, just viral protein that confers immunity
- HPV 2006, VLP, not whole, not one single viral protein but all structural viral proteins with no genome => not infectious
- Rotavirus vaccine (1998-2006) bovine-human ressortants
- Many different ways to make vaccines and can be human or animal vaccines and all tested to make the COVID vaccine
8
Q
Honourable mentions of vaccines (4 of them)
A
- MMR (3 in 1) live attenuated
- JEV (1992) inactivated/live attenuated
- Varicella (1995) live attenuated
- Hep A (1995) inactivated
9
Q
Advantages and disadvantages of live virus vaccines?
A
can replicate a bit to stimulate better immune response but dangerous if immunocompromised cause CAN cause disease
10
Q
SO what are some game-changing events in vaccinology?
A
- Jenner’s systematic study of cowpox like standard vaccine clinical trials
- Pasteur’s discovery of antimicrobial attenuation, his experiments with anthrax and rabies vaccines
- Discovery of antitoxin (target and neutralize toxins, useful of bacterial infections) and toxoids (attenuated/inactivated toxin, often adjuvants to enhance vaccine)
- Cultivation of viruses ex vivo (tissue cultures, grow and quantify)
- Recognitionn of polysaccharides as determinants of antigenic specificity for certain pathogens (pneumococcal polysaccharide vaccine to treat pneumonia in elders)
- Development of subunit vaccine
11
Q
What are immune correlates of vaccine protection?
A
- to determine if vaccine is effective or not
- Two correlates: persisting (pre existing) Ab in high levels and T cell responses (CTL to clear infection)
- Ab bind viral particles to neutralixe and prevent infectivity, F. regain can be bound by T cells and macrophages to clear/destroy infected cells => clearance of establishment of infection
12
Q
What are most important vaccine-induced antibodies and the source of persistent antibody responses?
A
- Mucosal IgA (protection at mucosal surfaces, all respiratory viruses nasal cavities, airway, mucosa and can traverse epithelial layer to lumen where can see and recognize and neutralize viruses, more than just reducing disease severity) and serum IgG (combat systemic infections (HIV, T cell and blood) and protect infection at mucosa though lower than mucosal IgA
- Long-lived plasma cells (PC) if pathogen detected, can quickly produce many Abs to clear pathogen, immune memory and produce Abs/reside in bone marrow, Ab production, response takes a lot of energy and resource, so that’s why when infection is resolved, serum Ab goes down, majority of long lived PCs reside in the bone marrow, but some may remain in the spleen and draining lymph nodes for years even decades
13
Q
What vaccines offer lifelong immunity?
A
chicken pox and Hep B
14
Q
Role of memory B cells in vaccine-mediated immunity
A
- Memory B cells provide a second line of defence since the 1st line is innate immunity which is not specific but only takes hours, while adaptive takes days
- Memory B cells are long-lived (decades)
- The role of memory B cells is not to block the infection nor maintain serum antibody levels but rather reduce disease severity following infection, this is the mechanism of COVID vaccine
15
Q
Contribution of memory T cells to vaccine-mediated protection
A
- Memory T cells do not directly block infection
- They can reduce or eliminate virus replication after infection has occurred through CTL from CD8 T cells
16
Q
What are benefits and risk of vaccines and how can we fix things?
A
- Attenuated or inactivated viruses have high protection efficacy but risk and subunit vaccines have low immunogenicity though low risk
- Solution to boost immunogenicity of subunit vaccines, formulation with adjuvant
17
Q
Roles of adjuvants
A
- Protect immunogènes from degradation in vivo (because more stable and can store for longer at 4 ºC or even RT) and enhance their targeting to dendritic cells (APCs to increase immunogenicity)
18
Q
Some licensed adjuvants
A
- Aluminum hydroxide (HBV, tetanus)
- MF59 (squalene droplets combined with two surfactants, used in influenza vaccines)
- AS04 (aluminum and bacterial lipid, used in GSK HPV vaccine)
- Toxoids (haemophilia influenza type b (Hib) vaccine)
19
Q
What are the criteria of successful vaccine?
A
- Safety (protects without causing other harm)
- Protective efficacy
- Cost (low to be more accessible to everyone)
20
Q
What is the current timeline and cost to produce a vaccine? Was it the same for the COVID vaccine?
A
- From concept to licensed product: 10-15 years
- Estimated cost: 500 to 800 million dollars due to phase I/II/III clinical trial
- COVID only 9 months, very hopeful for future pandemics
21
Q
What is the relation between vaccines and herd immunity?
A
- High vaccine coverage is required to acquire herd immunity, reduce transmission and protect vulnerable populations who may not be able to get vaccinated
22
Q
What are vaccinomics?
A
New term
- An integration of immunogenetics and immunogenetics with systems biology and immune profiling
- helps to understand immune responses to vaccines, identify correlates of protective immunity (Ab, T cell response, etc.), understand variations in an individual’s immune responses, design personalized vaccines (specifically for treatment of cancer)
23
Q
What is the difference between prophylactic and therapeutic vaccines?
A
- Most vaccines are prophylactic, given to prevent infection
- Some have therapeutic value, given as a post exposure prophylaxis like rabies vaccine
- Has some preexposure prophylaxis (given at high risk of contracting rabies, given in three doses, 0,7,21/28 weeks)
- Postexposure prophylaxis (given to those who are exposed to suspected or confirmed rabid animals, given together with rabies Ab in five doses 0,3,7,14 and 28 weeks)
24
Q
What are some human pathogenic viruses without vaccines?
A
HSV, HCV and HIV
25
What human pathogenic viruses recently got vaccines?
- Ebola (have one now)
- RSV approved this year, probably due to rise after then pandemic since the poor kids were not exposed young when they still had mum Abs due to isolation and masking and now BOOM and their immune systems are simply not trained
26
Why don't we have an HIV vaccine yet?
- Many ways have been tested to deliver HIV proteins to stimulate immune response (basically all ways to make vaccines, maybe not mRNA though)
HOWEVER
- High diversity of HIV subtypes and strains, may be too late, as time passes, more and more difficult to develop vaccine, almost impossible to make one to cover all Dif types and strains, think COVID and omicron in just two years just not as great with vaccine, however HIV vaccine research did help with COVID vaccine like stabilizing envelope proteins through modification in certain residues and keeping the virus in perfusion conformation so it doesn't infect cells
- Undefined correlates of protective immunity
- Lack of reliable animal models to test the vaccine cuz monkeys not infected by HIV-1 and chimpanzees cannot really be used due to ethical reasons
27
What are the criteria for an effective HIV vaccine?
- Induce broadly neutralizing Abs (at least 80-90% of Dif HIV strains)
- Induce cytotoxic T cell response in vast majority of recipients
- Induce strong mucosal immune responses bus major route of HIV transmission
28
What has been the most successful HIV vaccine clinical trial so far?
- 16000 volunteers, 8000 vaccine, 8000 placebo
- Two vaccines that's had failed individually were combined in hope of a miracle: ALVAC-HIV (env, ga and pol expression) and AIDSVAX B/E (genetically engineered gp120)
- results announced in 2009, only 31% protection and only for types B/E
29
What are the 4 COVID vaccine baddies?
- mRNA: pfizer, moderna lipid nanoparticles from SARS research and years of research to get mRNA technology
- Adenovirus vector vaccines: Oxford astrazenca, aJ and J
- Subunit vaccine: novavax (purified spike protein)
- Inactivated virus vaccine: SinoPharm
30
What is the COVID vaccine adherence like?
- Peak of vaccination mid-end 2021 and then another peak when omicron hit as people were getting their boosters
31
A few words on vaccine inequity
- Not a matter of income, it should not matter, it's a matter of equity, this is a global pandemic and we all need to be vexed bus variants come from large untaxed populations
