Vaccines L8-10 Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

Define vaccination.

A

The deliberate induction of an adaptive immune response by injecting a vaccine (a dead or attenuated, non pathogenic) form of the pathogen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Define immunization.

A

The act of making someone, something immune to a particular disease.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

____1____ can occur naturally or artificially.

____2____ can only occur artificially.

A
  1. Immunization
  2. Vaccination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Passive immunization

Protection by transfer of specific, high titre, antibody from an immune donor to a non immune recipient (____1____ transfer). Alternatively, immune cells from an immunized individual may be used to transfer immunity (____2____ transfer).

  • Gives immediate protection
  • Only offers transient effect and protection
A
  1. Passive
  2. Adoptive
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Read

Naturally acquired passive immunity

  • Required for neonatal protection
  • IgG is transferred from mother to foetus
  • Maternal IgA is transferred through colostral transfer
  • An IgG trough in neonates exists between 3-6 months of age due to the decline in maternal IgG.
A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the 3 month IgG trough.

A

Where the maternal IgG reduces and the child’s IgG is not high enough to make up for it.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Define artificially acquired passive immunity.

A

Artificially acquired passive immunity is a short-term immunization by the injection of antibodies, such as gamma globulin, that are not produced by the recipient’s cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

More than a thousand years ago, the Chinese tried to prevent smallpox by practice known as ____1____ (named after smallpox, or variola, virus). This involved peeling scabs from the lesions of smallpox survivors, drying and, grinding them to a powder and blowing them up the patient’s ____2____.

The effects of ____1____ varied ranging from mild illness in most individuals to death in a few.

A
  1. Variolation
  2. Nose
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Define immunological memory.

A

The ability of the immune system to respond more rapidly and effectively to a pathogen that has been encountered previously.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

The secondary response reflects a larger number of antigen-specific cells (memory cells) present after the primary response that have persisted (can be for decades).

During the initial expansion of antigen-specific B cell clones, some of the progeny cells do not develop into ____1____ cells. Instead, they revert to small lymphocytes bearing the same ____2____ on their surface (memory B cells).

These memory B cells respond more quickly and more effectively than naïve B cells.

A
  1. Plasma
  2. BCR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Immunological memory

Obviously no single cell can last 30+ years. Therefore the memory B cells must somehow pass on their memory to their progeny.

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

A secondary immune response produces antibody with increased ____1____. This comes about by the process of somatic hypermutation (SHM) which causes alterations in the ____2____ regions of light and heavy chains of the memory cells. This is a random process that improves antigen binding ____1____.

A
  1. Affinity
  2. Variable
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

When B cells bind an antigen in the primary response, they are selected for.

In the secondary response the new B cells have competition with the selected for antibodies. This selection process (which carries on into the tertiary response) selects for the antibodies with the greatest affinity to the ____1____.

This all takes place in ____2____ centres.

Is sort of a survival of the fittest (greatest affinity) scenario.

A
  1. Antigen
  2. Germinal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Compared to naïve B cells, memory B cells are what? (6)

A
  • Long lived
  • Have increased frequency
  • Proliferate more rapidly
  • Produce more antibody
  • Produce higher affinity antibody
  • Produce antibodies with better effector functions (IgG and IgA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

State the main difference between naïve T cells and memory T cells.

How does this knowledge help us?

A

CD45RA expressed on both types. CD45RO only expressed on memory T cells.

These therefore act as markers for distinguishing between them.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Memory T cells are long lived, have increased frequency and ____1____ more rapidly than naïve T cells.

Naïve T cells express the tyrosine phosphatase CD45RA which does not associate with the ____2____.

Memory T cells express CD45RO which associates with both the ____2____ and co-receptor (CD4). This complex tranduces signals more effectively than the receptor on naïve T cells.

A
  1. Proliferate
  2. TCR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q
  • Effector memory T cells (upon Ag re-stimulation, rapidly mature into effector cells) and move into tissues (lose ____1____ expression). Release lots of effector associated cytokines e.g. IFN-g and IL-4
  • Central memory T cells (mature into effector cells slower and stays in LN for longer due to maintenance of ____1____. Take longer to secrete effector associated cytokines.
A
  1. CCR7
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Define chemokine.

A

Molecules that the immune system secrete that help target the cells to the correct place.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is CCR7?

What is its function?

A

CCR7 is a chemokine receptor.

It detects the presence of chemokines. CCR7 binds to chemokines and keeps the cells in the lymph node.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Read

What must an effective vaccine do to induce memory?

  1. Be processed by APC for MHC presentation (generates Signal 1). Activate APC (induces co-stim (Signal 2) and Signal 3 (cytokines)
  2. Induce high levels of T and B cell primary activation, hence give a high efficiency of generating memory cells.
  3. Activate multiple T cell clones reactive with more than one epitope (to counter any antigenic variation of parasites).
  4. Provide a constant and long lasting source (depot) of antigen in lymphoid tissue.
  5. Induce protective response(s) to pathogen without causing disease.
A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

List the requirements of an effective vaccine. (8)

A
  • Safe
  • High level of protection
  • Long-lasting protection
  • Right type of response (local, systemic, antibody or T cells)
  • Low cost
  • Stable (often in high temperatures)
  • Easy to administer
  • Minimal side-effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

List the 5 types of active immunization.

A
  • Live attenuated vaccines
  • Killed vaccines
  • Sub-unit vaccines
  • Conjugate vaccines
  • Recombinant vaccines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

State the pros of live attenuated vaccines. (4)

A
  • Single dose effective
  • May be given by natural route
  • May induce local and systemic immunity
  • May induce right type of response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

State the cons of live attenuated vaccines. (4)

A
  • Reversion/alteration to virulence
  • Possibility of contamination
  • Susceptible to inactivation
  • Can cause disease in immunocompromised host
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Give examples of live attenuated vaccines (6)

A
  • Measles, mumps, rubella (MMR)
  • Oral polio (Sabin)
  • BCG
  • Yellow fever
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Give examples of killed vaccines. (4)

A
  • Salk polio vaccine
  • Pertussis (whooping cough)
  • Typhoid
  • Cholera.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

State the pros of killed vaccines. (2)

A
  • They are stable in storage
  • Killed vaccines are no longer pathogenic and therefore can no longer cause disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Recombinant Subunit Vaccines

To avoid the problems involved in bulk culture of pathogens recombinant vaccines have been introduced.

Hepatitis B was the first recombinant vaccine licensed for human use. Antibodies to Hepatitis B ______ antigen (HBsAg) are protective in natural infections.

A

Surface

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Purified Subunit Vaccines

These are vaccines that are made from purified components of pathogens. These components elicit protective immune responses, without the pathogenicity.

Give 2 examples.

A
  • HiB (Haemophilus influenza B which causes meningitis, pneumonia etc). The vaccine is made from purified capsular polysaccharides.
  • Influenza vaccine consists of purified haemagglutinin (H) and neuraminidase (N) antigens of the particular strain that is prevalent.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Define a conjugate vaccine.

A

A conjugate vaccine is created by covalently attaching a poor (polysaccharide) antigen to a carrier protein (preferably from the same microorganism), thereby conferring the immunological attributes of the carrier to the attached antigen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Give an example of a conjugate vaccine.

A

Haemophilus influenzae type b capsular polysaccharide conjugated to tetanus or diphtheria toxoid.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Define adjuvant.

A

A substance which enhances the body’s immune response to an antigen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Define herd immunity.

A

A form of indirect protection from infectious disease that occurs when a large percentage of a population has become immuneto an infection, thereby providing a measure of protection for individuals who are not immune.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Herd Immunity

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Recommended Vaccines in the UK

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Define DNA vaccination.

A

A technique for protecting an animal against disease by injecting it with genetically engineeredDNA so cells directly produce an antigen, resulting in a protective immunological response.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are the advantages of DNA vaccination? (3)

A
  • Limited or no virology
  • DNA is extremely robust
  • Less work, cheaper
38
Q

Expression plasmids used in DNA vaccination normally contain two units.

What are they?

A
  • Expression unit composed of promotor/enhancer sequences, followed by Ag encoding and polyadenylation (transcription terminator) sequences
  • The production unit composed of bacterial sequences necessary for plasmid amplification and selection.
39
Q

In DNA vaccination, the DNA is normally incorporated into a vector/______.

A

Plasmid

40
Q

Name the 3 types of DNA vaccine injection (where).

A
  • Intradermal
  • Intravenous
  • Intramuscular
41
Q

The skin and mucous membranes are best sites for DNA vaccine injections due to high concentrations of resident ______.

A

APCs

42
Q

DNA vaccination: administration

Gene Gun: biolistic (bioballistic) method where under certain conditions DNA (or RNA) become ‘sticky’ adhering to biologically ____1____ particles such as tungsten or gold.

By accelerating this complex in a partial ____2____, and placing target tissue in the acceleration path, DNA can be effectively introduced into living cells.

A
  1. Inert
  2. Vacuum
43
Q
A
44
Q

Read

DNA vaccination: in practice

  • Ag that resemble native epitopes can be synthesized. Epitopes often lost in inactivated/attenuated conventional protein vaccines
  • If APC are targeted, Ag can access MHC I and II pathways, thus CD8, CD4 and B cell responses can be induced
  • DNA vaccines can be constructed and produced more efficiently/reduced time and costs for large scale ups c.f. proteins
  • Vaccines encoding several different Ag (incl. adjuvants) can be delivered in single doses.
A
45
Q

What are the disadvantages of DNA vaccination? (2)

A
  • Many pathogens have outer capsids made of polysaccharides. This limits the use of DNA vaccines as they cannot substitute for polysaccharide based subunit/congugated vaccines.
  • Extended immuno stimulation can lead to chronic inflammation
46
Q

DNA vaccination: administration

DNA tattooing

  • Delivers DNA into the skin through thousands of punctures made with a multiple needle tattoo device.
  • Results in local ____1____ and expression of the encoded antigen by cells in murine skin
  • DNA tattooing has been shown to induce ____2____ vaccine specific immune responses in mice.
A
  1. Transfection
  2. Strong
47
Q

Dengue is caused by one of four closely related but distinct virus serotypes (DEN1, DEN2, DEN3 and DEN4) of the family Flaviviridae.

It is transmitted by the bite of a ____1____ and can cause symptoms ranging from ____2____-like symptoms to death. Approximately 100 million people are infected with Dengue every year in tropical and sub-tropical countries with about 20 000 deaths.

A
  1. Mosquito
  2. Flu
48
Q

Define serotype.

A

Distinct variations within a species of bacteria, virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their cell surface antigens.

49
Q

Read

DNA vaccination: ongoing human trials

  • H5N1 avian influenza (2011) – Immune response to H5N1 protein enhanced if adults primed with H5N1 vaccine (prime-boost strategy). H7N9 vaccine in pre-clinical trials
  • Multiple sclerosis (August 2007)–Myelin DNA was injected into 30 patients suffering from relapsing MS. Anti-myelin immune responses fell in these patients (induction of tolerance). This trial was extended to 290 patients – no results available?
  • West Nile Virus (2007) – approved for horses
  • Ebola virus (2005/06)- phase 1. (2010) Monkeys protected with prime boost strategy – DNA vaccine then Ebola proteins. Shown to be safe in humans.
  • ADVAX (anti-HIV vaccine) (2004-2012). Elicits CD4 and CD8 responses
  • Prostate Cancer (range of phase I and II trials) – shows CD8+ cells generated
A
50
Q

What are the main recruiter of CD4 T cells?

A

Dendritic cells

51
Q

Read

Dendritic cell (DC)-based vaccines

  1. Process and present Ag. to T cells
  2. Take up antigen by numerous means
  3. Thought to be first cell to take up Ag.
  4. Simultaneously activated by “danger” (PRR) to express co-stimulation molecules
  5. Migrate from peripheral site to lymph node and initiate (“prime”) immune response by presenting Ag. and activating naïve T cells
  6. Short lived to prevent prolonging of response
A
52
Q

CD80 and ______ are the co-stimulatory molecules that dendritic cells express to activate T cells.

A

CD86

53
Q

Dendritic cells (DCs) are antigen-presenting cells of the mammalian immune system. Their main function is to process antigen material and present it on the cell ____1____ to the T cells of the immune system. They act as messengers between the innate and the ____2____ immune systems.

A
  1. Surface
  2. Adaptive
54
Q

Dendritic cell function

A
55
Q

What is the main source of DCs for clinical trials?

A

CD34+ blood or bone marrow derived precursors that are initially cultured in vitro.

56
Q

Quite often in tumour biology we don’t actually know which part of the tumour is the ____1____ bit (the important tumour antigen). So we can take the patients tumour and lyse it before adding the lysate to the dendritic cells. This causes the DCs to process the ____2____ and present them effectively.

This is why DC vaccination could be key when we do not know the tumour Ag.

A
  1. Immunogenic
  2. Proteins
57
Q

DC vaccination procedure

DC ____1____ are collected from the blood, differentiated ex-vivo and loaded with tumour Ag(s). Differentiating and loading the DC takes approximately ____2____ days. The resultant cells are then aliquoted and frozen in liquid nitrogen. The patient can then be vaccinated subcutaneously with their own Ag-loaded DC.

A
  1. Precursors
  2. 3
58
Q

With DC vaccines we are not limited to finding the ultimate antigen like in some other vaccines. We can just mash up the ____1____ cells and let the DCs find it.

Also as the immunogenic antigens differ, even in the same cancer, DC vaccination means we don’t have to constantly search for the antigen ____2____ to the patient.

A
  1. Tumour
  2. Specific
59
Q

Read

Reverse vaccinology

Use of bioinformatics to predict the proteins located in an organisms surface and candidate vaccines.

Using this method for meningococci there were 600 predicted proteins identified in silico (computational biology).

Of these, 350 were successfully expressed in E.coli as fusion products, purified and used to immunise mice.

There were 91 novel surface proteins identified, 29 of these induced bactericidal antibodies – a prediction of a good vaccine candidate.

Prior to this, only 12-15 had been identified and only 4 –5 of these had bactericidal properties.

Vaccine candidates are in clinical trials.

A
60
Q

Describe reverse vaccinology.

A

Use of bioinformatics to predict the proteins located in an organisms surface and candidate vaccines.

61
Q

What are the advantages of reverse vaccinology. (5)

A
  • Fast access to virtually every Ag
  • Non-cultivable organisms can be approached – the whole organism does not need to be grown to produce Ag
  • Non-abundant antigens can be identified – less common Ag which may be immunogenic can be identified
  • Ag not expressed in vitro can be identified
  • Non-structural proteins can be used
62
Q

______ cancer is the 2nd most common cancer in women with ~500, 000 new cases and 270 000 deaths annually.

______ screening using the smear test has been available in the UK since the 1967. In spite of this there was still 3064 new cases of cervical _______ in 2011 (UK) and 919 deaths in 2012 (Cancer Research UK).

A

Cervical

63
Q

Human papillomaviruses (HPV) is a ____1____ transmitted infection that invades ____2____ cells.

There are at least 120 types of HPV and of these 18 are associated with cervical cancer. HPV16 and 18 cause 70% of cervical cancer.

HPV 6 and 11 cause ____3____ % of cases of genital warts.

Merck and Co, Inc developed a vaccine against HPV 6, 11, 16 and 18 (Gardasil) which was been licensed in the UK in 2006.

GlaxoSmithKline also licensed a vaccine in 2007 (Cervarix).

A
  1. Sexually
  2. Epithelial
  3. 90
64
Q

HPV vaccines and cervical cancer

DNA free virus like particles (VLP) have been manufactured in Saccharomyces cervisiae.

These VLP express the major ____1____ antigen (L1) of HPV and induce a strong immune response.

The neutralizing ____2____ produced prevent infection of cells by HPV.

A
  1. Capsid
  2. Antibodies
65
Q

Read

21,000 women between the ages of 16 and 26 were vaccinated with HPV vaccine (Gardasil). In women who had not already been infected with HPV Gardasil was nearly 100 percent effective in preventing precancerous cervical lesions, precancerous vaginal and vulvar lesions, and genital warts.

The studies also evaluated whether the vaccine can protect women already infected with HPV from developing diseases related to those viruses. The results show that the vaccine is only effective when given prior to infection.

A
66
Q

What microorganism causes malaria?

A

The protozoa of the genus Plasmodium.

67
Q

Malaria is transmitted by female mosquitos of a specific genus.

Name the genus.

A

Anopheles

68
Q

______ _______ is the most wide spread, pathogenic and drug resistant malaria causing protozoa.

A

Plasmodium falciparum

69
Q

Uncomplicated Malaria

The first symptoms are non-specific and resemble ____1____. Headache, muscular ache, vague abdominal discomfort and lethargy often precede fever by up to 2 days. After this the ____2____ rises erratically at first with shivering, mild chills and a worsening headache.

If the infection is left untreated, fever with P.vivax, P.ovale and P.falciparum recurs every 48 hours and for P. malariae every 72 hours.

As the ____2____ rises there is intense headache and muscular discomfort. The patient will feel cold and starts ____3____. Within minutes the limbs begin to shake and teeth chatter.

The rigor usually lasts for 10-30 minutes. At the end of the rigor the skin feels hot due to peripheral vasodilation and a profuse sweat will break out.

Defeverescence (reduction in temp.) usually takes 4-8 hours.

As the infection continues the spleen and liver enlarge and ____4____ develops. The patient will lose weight. If no treatment is given the infection will stabilize for several weeks or months and then gradually resolve.

A
  1. Influenza
  2. Temperature
  3. Shivering
  4. Anaemia
70
Q

Malaria - relapse

P.vivax and P.ovale have a tendency to relapse after the primary infection due to ____1____ of persistent hypnozoites in the ____2____.

Relapses can occur weeks, months or years after the primary infection.

A
  1. Maturation
  2. Liver
71
Q

In ______ malaria, the parasite goes to the brain, and is much more dangerous.

A

Cerebral

72
Q

Malaria in pregnancy

In areas of intense transmission the principal impact of P. falciparum malaria in pregnancy there is an increased incidence of ____1____ and a reduction in birth weight of babies.

If pregnant women develop severe malaria ______ 2 ______ is common.

Mortality from cerebral malaria in pregnancy is approximately 50% in pregnant women as compared to 20% in non-pregnant women.

A
  1. Anaemia
  2. Foetal loss
73
Q

Severe malaria

Death from acute P. vivax, P. ovale or P. malariae malaria is very rare. _.______ malaria is potentially fatal. The progression to severe disease is rapid. Severe malaria is rare in malnourished children and often affects the healthiest people.

A

P. falciparum

74
Q

The immune response to malaria is what kills the host. The parasite causes lots of ______ to be released leading to fever and death.

A

Cytokines

75
Q

Cerebral malaria

In cerebral malaria the onset of coma may be sudden, often following a generalized ____1____. The duration of coma varies considerably but is shorter in children than adults (1 day to 2-3 days). Untreated cerebral malaria is uniformly ____2____. The case fatality rate in treated children is 10%-40%.

A
  1. Seizure
  2. Fatal
76
Q
A
77
Q

Malaria vaccine – pre-erythrocytic disease prevention

The primary objective of pre-erythrocytic stage vaccines is provision of a level of protection that prevents any invasion of the ____1____ and hence any clinical malaria.

This has been achieved readily in experimental malarias by vaccination with radiation-____2____ sporozoites.

Complete protection was also achieved in humans against P. falciparum and P. vivax by exposing them to the bites of mosquitoes that had been irradiated to attenuate their sporozoites. However, this delivery procedure was totally impractical for use in the field.

A
  1. Blood
  2. Attenuated
78
Q

Pre-blood stage malaria vaccines

Knowing the biology of the parasites, we know that we have about 1 month from when the parasite enters the host to when it accesses the liver. The immune response to clear the parasite must happen before they can hide in the liver.

A
79
Q

Read

Malaria Vaccine – pre-erythrocytic disease prevention

There has been a renewal of interest in the development of attenuated-sporozoite vaccines (PfSPZ vaccine).

Phase I clinical trials have shown the vaccine to be safe, immunogenic and that it triggers high levels of malaria specific CD8+ T cells.

A recent Phase II trial has shown that 0/6 subjects receiving 5 doses and 3/5 subjects receiving 4 doses of 1.35 x 105 PfSPZ vaccine and 5/6 non vaccinated controls developed human malaria.

Prior to this the RTS, S/AS01 vaccine candidate was considered to be the most promising vaccine to date.

This vaccine is a hybrid molecule expressed in yeast, that consists of the tandem repeat tetra-peptide (R) and C-terminal T-cell epitope containing (T) regions of CSP (circumsporozoite protein) fused to the hepatitis B surface antigen (S), plus unfused S antigen.

The first challenge trials with RTS, S/ASO2 gave impressive, but short-lived, protection in naïve adults

Similarly, in a trial in Gambian adults, there was greater than 70% protection against parasitaemia in the nine weeks post-vaccination, but the immunity waned rapidly.

Adjuvants ASO2, which consists of an oil in water emulsion containing monophosphoryl lipid A and QS-21, a fraction of the inner bark from Quillaia saponaria (Soapbark tree) are essential components of this vaccine.

The latest trials with this vaccine show:

  • In large Phase 3 trials in African infants (6-12 weeks) RTS,S/ASO1 reduced the rates of clinical and severe malaria acquired over a 12 month period by 31.3% and 36.6%
  • Approx. 50% of subjects are protected against controlled human malaria infection 2-3 weeks after the last dose of vaccine and 22% at 5 months after the last immunization

In July 2014 GSK applied for a regulatory application to the European Medicines Agency for the RTS vaccine. If approved by EU may then go onto potential approval by WHO.

A
80
Q

______ malaria is caused by blood stage parasitemia and acquired immunity in humans largely targets blood stage antigens.

A

Symptomatic

81
Q

Read

Malaria vaccine – transmission blocking

The concept of a inducing antibodies targeted against sexual-stage specific surface molecules (Pfs 48/45 and Pfs 230) in P. falciparum that would be ingested by feeding mosquitoes was developed 30 years ago.

Experimentally, sera from rabbits, monkeys and mice vaccinated with the vaccine candidates Pfs25 from P. falciparum and Pvs25 from P. vivax contained antibodies with transmission-blocking activity.

Phase 1 human vaccine trials with the Pfs25 have also been effective though not yet at the level that will be required and can be achieved experimentally.

A conjugate of Pfs25H Ag linked to a detoxified form of Pseudomonas aeruginosa exoprotein A (EPA) has recently been developed for use in human clinical trials.

The Pfs25-EPA conjugate nanoparticle induced 75-110x increase in Pfs25H specific antibodies in mice compared to unconjugated Pfs25H.

A phase 1 trial is ongoing in humans with this conjugate vaccine.

A
82
Q

What kind of virus is the Ebola virus?

How many genes does it contain?

A

ss RNA filovirus

7

83
Q

Which cell types does the ebola virus infect? (3)

How does it gain entry? (2)

A

Ebola mainly infects endothelial cells, mononuclear phagocytes and hepatocytes.

Via C-type lectins and integrins.

84
Q

Ebola virus encoded glycoprotein (GP) and its secreted form (sGP) play an essential role in the pathogenesis of ______ ______ ______ (EVD).

A

Ebola Virus Disease

85
Q

Name the microorganism that causes tuberculosis.

A

Mycobacterium tuberculosis

86
Q

The tuberculosis vaccine, BCG, was first used in 1921 and has been given to more people than any other vaccine.

BCG (Bacille Calmette Guerin) contains a ______ 1 ______strain of Mycobacterium bovis.

The vaccine prevents TB meningitis in children but has very little ____2____ against adult pulmonary disease.

A
  1. Live attenuated
  2. Efficacy
87
Q

The blocking hypothesis suggests that natural immunity to environmental Mycobacterium bovis that develops with age impairs the vaccine effect of BCG in adults to protect against Mycobacterium tuberculosis.

Thus a better vaccine for Mycobacterium tuberculosis. would have what features/be given when? (3)

A
  • Given at birth as a non-living formulation
  • Be a transmitting blocking vaccine that would decrease the positivity of sputum smears
  • Be a therapeutic vaccine that could be used in adjunct with therapy to shorten current treatment protocols.
88
Q

Currently the most promising TB vaccine is the MVA85A vaccine

This is a ____1____ modified vaccinia virus Ankara expressing Mycobacterium tuberculosis Ag 85A.

Ag 85A is immunodominant in human studies and is protective in small animals.

In phase 1 trials in volunteers who had been vaccinated produced substantially higher levels of mycobacterium specific IFN-g secreting ____2____ cells as compared to those individuals given a single BCG boost.

Phase II trials have shown that the vaccine is well tolerated and safe in patients with HIV and M. tuberculosis.

A
  1. Recombinant
  2. T
89
Q

Define recombination.

A

The rearrangement of genetic material, especially by crossing over in chromosomes or by the artificial joining of segments of DNA from different organisms.

90
Q

Upon Ag re-stimulation, effector memory T cells rapidly mature into effector cells and move into tissues (lose ___1___ expression). They release lots of effector associated ___2___ e.g. IFN-g and IL-4.

A
  1. CCR7
  2. Cytokines
91
Q

Describe somatic hypermutation.

A

Somatic hypermutation involves a programmed process of mutation affecting the variable regions of immunoglobulin genes in order to improve antigen binding affinity.