Vaccine Development

Question 1

what is inoculation?

Answer 1

live virus was administered to healthy individuals

Question 2

how did the smallpox vaccine come to be?

Answer 2

In the 18th century in Europe, 400,000 people died annually of smallpox, and it was common knowledge that survivors of smallpox became immune to the disease

Some communities tried to lessen the likelihood of death by scratching into their skin scab material from someone with a mild form of smallpox. This practice of deliberately giving people smallpox was later called “inoculation” or “variolation.”

Unfortunately, however,the identification of a suitable strain of the disease was not a precise science, and deaths from inoculation were not uncommon

Question 3

what is cowpox and how was it related to smallpox?

Answer 3

Being intrigued by country-lore which said that milkmaids who caught cowpox from their cows could not catch smallpox, Edward Jenner inoculated an 8-year-old boy using matter from a cowpox skin lesion of a milkmaid in 1796

A few days later, the became mildly ill with cowpox, but was well again a week later. Importantly, the boy was subsequently found to be fully protected against smallpox.

Jenner’s work represents the first scientific attempt to control an infectious disease by the deliberate use of vaccination.

In 1980, the WHO declared smallpox an eradicated disease.

Question 4

what’s the concept behind vaccines?

Answer 4

initial exposure to a pathogen induces antibody and T cell responses to various pathogen-associated antigens, but with a significant delay

when exposed to the same pathogen, immune responses can be generated more promptly

even when infected with the same pathogen years later, the individual is protected with immunological memory

vaccines are designed to mimic natural infection in immunological consequences.

Question 5

why do some vaccines require a series with multiple doses?

Answer 5

most vaccines require multiple doses to induce long-lasting protective immunity

the first immunization most likely induces relatively weak immune responses with no immunological memory

upon the second immunization, some individuals may exhibit relatively strong immune responses with memory

most individuals acquire potent protective immunity with long-lasting memory only after repeated immunizations

note that some vaccines induced detectable immune responses only after the second immunization

Question 6

what is a live attenuated vaccine?

Answer 6

live viral particles with extremely low virulence are administered

since they reproduce (albeit slowly), boosters are required less often

there is a small risk of reversion to virulence

attenuated vaccines cannot be given to immuno-compromized individuals

Question 7

what are some examples of live attenuated vaccines?

Answer 7

measles/mumps/rubella (MMR)

Sabin polio

varicella (chicken pox virus)

rotavirus

Question 8

what are inactivated vaccines?

Answer 8

viral particles are heat-killed or fixed with formaldehyde before administration.

since they do not reproduce, repeated boosters are required to induce immune responses with memory

Question 9

what are some examples of inactivated vaccines?

Answer 9

influenza

rabies

Salk polio

Question 10

what are subunit vaccines?

Answer 10

purified proteins from virus or bacteria are administered as antigens

since isolated proteins may have different 3D structures from native forms, antibodies elicited with subunit vaccines may not recognize infectious organisms

bacterial toxins are detoxified with formalin treatment before administration (toxoid vaccines)

polysaccharides purified from bacterial outer capsules are poorly immunogenic

when conjugated to carrier proteins (e.g., bacterial toxins), they produce potent antibody responses (conjugate vaccines)

some viral structural proteins (Envelop and Capsid) can self-assemble into virus-like particles (VLP), which are then administered as VLP vaccines

Question 11

what are some examples of subunit vaccines?

Answer 11

diphteria/tetanus/pertussis (DTP)

pneumococcal conjugate

Haemophilus B conjugate (HiBC)

meningococcal C conjugate

hepatitis B

human papillomavirus vaccines

Question 12

what are the three types of vaccines?

Answer 12

1. live attenuated vaccines
2. inactivated vaccines
3. subunit vaccines

Question 13

what is the mechanism for immune protection that live attenuated vaccines and inactivated vaccines use?

Answer 13

these vaccines are expected to trigger both humoral and cell-mediated immune responses against multiple viral antigens

neutralizing antibodies against viral surface components can block initial attachment and/or entry of viral particles to host cells. CD4+ helper T cells recognizing viral antigens expressed on MHC class II molecules help antibody production

moreover, CD8+ cytotoxic T cells recognizing viral antigens expressed on MHC class I molecules can kill virally infected host cells directly, thereby blocking viral replication

Question 14

what is the mechanism for immune protection that viral subunit vaccines and virus-like particle vaccines use?

Answer 14

these vaccines primarily induce neutralizing antibodies against viral surface proteins, which can block initial attachment and/or entry of viral particles to host cells

Question 15

what is the mechanism for immune protection that toxoid vaccines use?

Answer 15

toxic proteins secreted by pathogenic bacteria cause major clinical symptoms in certain bacterial infections.

toxoid vaccines are designed to induce neutralizing antibodies against these bacterial toxins

Question 16

what is the mechanism for immune protection that capsular polysaccaride vaccines use?

Answer 16

certain pathogenic bacteria express unique polysaccharides in the outer capsules, and these polysaccharides can potentially serve as species-specific and strain-specific antigens

to enhance the immunogenicity, the polypeptides are conjugated with carrier proteins

conjugate vaccines produce antibodies that bind to the capsules, fix complement, and kill bacteria

Question 17

what vaccine is used for diphtheria? is diphtheria a bacteria or virus?

Answer 17

bacteria

toxoid vaccine

Question 18

what vaccine is used for tetanus? is tetanus a bacteria or virus?

Answer 18

bacteria

toxoid vaccine

Question 19

what vaccine is used for pertussis? is pertussis a bacteria or virus?

Answer 19

bacteria

killed bacteria or subunit vaccine composed of pertussis toxoid and other bacterial antigens

Question 20

what vaccine is used for paratyphoid fever? is paratyphoid fever a bacteria or virus?

Answer 20

bacteria

killed bacteria vaccine

Question 21

what vaccine is used for typhus fever? is typhus fever a bacteria or virus?

Answer 21

bacteria

killed bacteria vaccine

Question 22

what vaccine is used for cholera ? is cholera a bacteria or virus?

Answer 22

bacteria

killed bacteria or cell extract vaccine

Question 23

what vaccine is used for plague? is plague a bacteria or virus?

Answer 23

killed bacteria or cell extract vaccine

Question 24

what vaccine is used for tuberculosis? is tuberculosis a bacteria or virus?

Answer 24

bacteria

attenuated strain of bovine vaccine

Question 25

what vaccine is used for typhoid fever? is typhoid fever a bacteria or virus?

Answer 25

bacteria vi polysaccharide subunit vaccines live-attenuated oral vaccine

Question 26

what vaccine is used for meningitis? is meningitis a bacteria or virus?

Answer 26

bacteria purified capsular polysaccharide vaccine

Question 27

what vaccine is used for pneumonia? is pneumonia a bacteria or virus?

Answer 27

bacteria purified capsular polysaccharide vaccine

Question 28

what vaccine is used for yellow fever? is yellow fever a bacteria or virus?

Answer 28

virus attenuated virus vaccine

Question 29

what vaccine is used for measles? is measles a bacteria or virus?

Answer 29

virus attenuated virus vaccine

Question 30

what vaccine is used for mumps? is mumps a bacteria or virus?

Answer 30

virus attenuated virus vaccine

Question 31

what vaccine is used for rubella? is rubella a bacteria or virus?

Answer 31

virus attenuated virus vaccine

Question 32

what vaccine is used for polio? is polio a bacteria or virus?

Answer 32

virus attenuated virus or killed virus vaccine

Question 33

what vaccine is used for varicella? is varicella a bacteria or virus?

Answer 33

virus attenuated virus vaccine

Question 34

what vaccine is used for influenza? is influenza a bacteria or virus?

Answer 34

virus inactivated virus

Question 35

what vaccine is used for rabies? is rabies a bacteria or virus?

Answer 35

virus inactivated virus vaccine (humans) attenuated virus vaccine (dogs and other animals) recombinant live vaccine )animals)

Question 36

what vaccine is used for hep A/B? is hep A/B a bacteria or virus?

Answer 36

virus subunit vaccine (recombinant hepatits antigen)

Question 37

what vaccine is used for HPV? is HPV a bacteria or virus?

Answer 37

virus subunit vaccine (virus coat protein)

Question 38

what vaccine is used for rotavirus? is rotavirus a bacteria or virus?

Answer 38

virus attenuated virus or recombinant live virus vaccine

Question 39

how do you produce attenuated viruses?

Answer 39

1. the pathogenic virus is isolated from a patient and grown in human cultured cells 2. the cultured virus is used to infect monkey cells 3. the virus acquired many mutations that allow it to grow well in monkey cells 4. the virus no longer grows well in human cells (it is attenuated) and can be used as a vaccine

Question 40

what are the requirements of an attenuated vaccine?

Answer 40

an attenuated vaccine requires a mutant virus that is non-pathogenic in humans, while maintaining antigenic surface proteins of the original virus such a virus can be produced by growing the wild-type virus in cells of non-human origin

Question 41

what is the best vaccine that leads to the strongest adaptive immune response?

Answer 41

natural infection with pathogenic microbes can induce full protection from the subsequent infection with the same microbes. of all the currently available vaccine types, the live attenuated vaccines elicit the most potent immune responses, including humoral responses and T cell-mediated responses (see Slide13). the component (or subunit) vaccines induce only humoral responses thus, live attenuated vaccines are the first choice in terms of the resulting immune responses

Question 42

when someone gets a natural infection, which part of the immune system is activated?

Answer 42

natural infection with pathogenic microbes produces potent immune responses because they introduce foreign antigens, microbial products (which activate Toll-like receptors), as well as tissue damages (which induce inflammation) so it can activate both adaptive and innate arms of the host immune system a natural pathogenic infection has: 1. foreign antigens 2. microbial products 3. tissue damage

Question 43

when someone gets a subunit vaccine, what parts of the immune system are activated?

Answer 43

component (or subunit) vaccines provide only foreign antigens there are no microbial products or tissue damage in the absence of microbial products or tissue damages, component (or subunit) vaccines activate only the adaptive immunity

Question 44

what type of vaccine is the safest?

Answer 44

contrary to the relative potency, component (or subunit) vaccines are the first choice in terms of the safety

Question 45

what is the relative safety of the types of microbes that could be in vaccines?

Answer 45

least safe 1. live pathogenic microbes 2. live attenuated microbes 3. killed microbes 4. microbial components most safe

Question 46

what are adjuvants?

Answer 46

components in vaccine formulations that are added to enhance the resulting immune responses they augment adaptive immune responses by otherwise weak vaccines

Question 47

what is in-water and oil-in-water emulsion?

Answer 47

both types of adjuvant oil-in-water helps antigen retention at the vaccination site and antigen uptake by professional antigen presenting cells in-water emulsion is used for dead mycobacteria mycobacterial products trigger innate immune responses (i.e., tissue inflammation) and APC activation via binding to Toll-like receptors and other receptors

Question 48

what are the only currently approved adjuvants?

Answer 48

Alum and MF59 due to safety concerns

Question 49

what is Freund's incomplete adjuvant?

Answer 49

oil-in-water emulsion it delays the release of the antigen which enhances uptake by macrophages

Question 50

what is Freund's complete adjuvant?

Answer 50

oil-in-water emulsion with dead mycobacteria it delays release of antigen which enhances uptake by macrophages and induces co-stimulators in macrophages

Question 51

what is Freund's adjuvant with MDP?

Answer 51

oil-in-water emulsion with MDP (a constituent of mycobacteria) it's similar to Freund's completely adjuvant

Question 52

what is Alum?

Answer 52

aluminum hydroxide gel delays release of antigen and enhances macrophage uptake

Question 53

what is Alum plus?

Answer 53

aluminum hydroxide gel with killed B. pertussis delayed release of antigen which enhances uptake by macrophages and induces co-stimulators

Question 54

what is immune stimulatory complexes?

Answer 54

ISCOMs is a matrix of lipid micelles containing viral proteins delivers antigen to cytosol which allows induction of cytoxic T cells

Question 55

what is MF59 adjuvant?

Answer 55

squalene-oil-emulsion delayed release of antigen

Question 56

what's the difference between MHCI and MHCII?

Answer 56

antigens incorporated from extracellular space are presented on MHC class II molecules to CD4 T cells antigens being produced within APC are presented on MHC class I molecules to CD8 T cells

Question 57

what were ISCOM made to do?

Answer 57

ISCOM = immune stimulatory complexes (adjuvant) were developed in an attempt to load peptide antigens on MHC class I molecules for the induction of cytotoxic T cell responses lipid micelles containing peptide antigens are designed to fuse with cell membrane, thus, delivering the antigens directly into the cytosol of APC

Question 58

which cytokine stimulates the production of TH1?

Answer 58

IL-12 and IL-2

Question 59

which cytokine stimulates production of TH2?

Answer 59

IL-4 and IL-2

Question 60

how do DNA-based vaccines work?

Answer 60

attenuated microorganisms genetically engineered to express DNA encoding immunogenic antigens derived from a pathogen (e.g., HIV-1) are administered via oral or subcutaneous route the microorganisms produce recombinant antigens in the GI tract or skin, thereby, eliciting pathogen-specific immune responses in the recipients alternatively, DNA encoding immunogenic antigens can be administered directly to humans via needle injection or gene gun-mediated skin delivery system recombinant antigens are then synthesized by host cells themselves, thus, eliciting pathogen-specific immune responses in the recipients.

Question 61

ideal vaccines have which characteristics?

Answer 61

1. since vaccines are administered to healthy individuals, they must be absolutely safe. 2. since vaccines are often administered to children, they must be painless 3. they must elicit potent and long-lasting immunity after single administration 4. they must induce the most desired types of immune responses (e.g., antibody response versus cytotoxic T cell response) depending upon the target pathogen 5. considering the use in developing countries, they must be cheap and stable without refrigeration 6. considering the application to newly emerging pathogens, they must be manufactured fast within a few weeks after an endemic

Question 62

which diseases do we still not have a vaccine for?

Answer 62

HIV/AIDS (2 million) tuberculosis (1.5 million) malaria (1 million) diarrheal disease (2.2 million) respiratory infections (4 million)