L10 - Immunology of the gut mucosa 2 - Jamie Mann Flashcards
- Understand the concepts of mucosal immunity and its importance in vaccine development - Explain the differences between mucosal vaccines and traditional injectable vaccines in terms of administration, mechanism of action and advantages - Describe the challenges and barriers associated with developing effective mucosal vaccines - Discuss the various mucosal vaccine delivery routes and their advantages and limitations (159 cards)
1
Q
How are traditional vaccines generally administered?
A
Traditional vaccines are typically administered systemically, meaning they are delivered through:
- Intramuscularly (into the muscle)
- Subcutaneously (into the subcutaneous layer)
- Intradermally (into the dermis)
(Most vaccines are administered intramuscularly, with fewer being given intradermally or subcutaneously)
2
Q
what are example intramuscular vaccines
A
Influenza and Diptheria
3
Q
what are example subcutaneous injections
A
MMR and IPV
4
Q
what are example intradermal injections
A
BCG
5
Q
What are live attenuated vaccines and how do they work?
A
Live attenuated vaccines use viruses that have been cultured or engineered to remain infectious while having reduced infectivity. These viruses can infect a small number of cells but are less virulent and cannot replicate efficiently. This limitation triggers a strong immune response, as dendritic cells capture the virus and present it to T cells to stimulate the immune response, without overwhelming the body like a traditional pathogen could.Live attenuated vaccines use viruses that have been cultured or engineered to remain infectious but with reduced infectivity.
- The virus can infect a few cells but is less fit and cannot replicate efficiently.
- This triggers a robust immune response without overwhelming the body like a traditional pathogen would
6
Q
What are killed pathogen vaccines?
A
Killed pathogen vaccines use viruses or bacteria that have been inactivated so they cannot replicate or cause infection.
Their purpose is to be taken up by dendritic cells and presented to T cells to stimulate an immune response.
7
Q
what are examples of live attenuated virus vaccines
A
examples for live attenuated virus vaccines include those for Rubella and Mumps
8
Q
What are toxin-based vaccines?
A
Toxin-based vaccines are designed to generate immunity against bacterial toxins.
9
Q
What are some examples for toxin based vaccines
A
Examples include vaccines for diphtheria and pertussis, where toxins are engineered to be safely presented to the immune system.
10
Q
What are two new platforms for vaccines
A
- RNA vaccines
- Viral vectors
11
Q
What are RNA vaccines ?
A
RNA Vaccines: Use messenger RNA to encode antigens that stimulate an immune response.
12
Q
What are viral vector vaccines
A
Viral Vector Vaccines: Use a harmless virus as a delivery system to introduce genetic material coding for antigens.
Both types were widely used during the COVID-19 pandemic.
13
Q
What are the limitations of traditional vaccines?
A
Traditional vaccines are effective at generating systemic immune responses (e.g., circulating antibodies and T cells in the blood). However, they have limited effectiveness against certain global pathogens, including:
- HIV
- Malaria
- Tuberculosis (TB)
These pathogens require different immune strategies for effective protection.
14
Q
What is the current status of HIV vaccine development?
A
Despite extensive research, no effective vaccine for HIV has been developed.
Most clinical trials have shown no efficacy in preventing HIV acquisition.
One trial, known as RV 144 (or the Thai trial), showed modest protective efficacy of about 31%, but this result was never replicated in subsequent studies.
15
Q
How long has the search for an HIV vaccine been ongoing?
A
Research has been ongoing for over 40 years, since the identification of HIV as the etiological agent behind the global AIDS epidemic in 1980.
Despite decades of research, an effective vaccine has yet to be developed.
16
Q
How prevalent is TB globally, and what is its impact?
A
TB infects about 25% of the global population, and a significant number of people die from it every year, making it a major public health concern.
17
Q
What type of vaccine is the BCG vaccine, and what is it derived from?
A
The BCG vaccine is a live attenuated vaccine derived from the Mycobacterium bovis strain, which primarily infects cows.
18
Q
How effective is the BCG vaccine, and what are its limitations?
A
The efficacy of the BCG vaccine is variable:
- Effective in young children (under five years) but efficacy declines in adults and older children.
- Provides protection against pulmonary TB but is less effective against extrapulmonary TB.
- It reduces the severity of disease and protects against death but does not necessarily prevent infection.
19
Q
What is the latest development in TB vaccine research?
A
A new tuberculosis (TB) vaccine is currently undergoing clinical trials.
In a study involving 3,300 participants, half received the vaccine while the other half received a placebo. Out of all participants, only 40 developed TB, with a significantly higher number of cases occurring in the placebo group. The vaccine demonstrated approximately 50% efficacy in reducing the acquisition of TB.
20
Q
What immune responses were observed in the new TB vaccine trial?
A
The trial showed:
- Rapid antibody response peaking at 2 months post-vaccination, followed by a plateau.
- Elevated antibody levels were maintained for 36 months, indicating durability.
- T cell responses were also durable, remaining elevated after 36 months.
21
Q
Why are there large standard deviations in the immune response data for the new TB vaccine?
A
The large standard deviations are due to the vaccine being tested in a wild-type human population with:
- Genetic diversity and social factors influencing immune responses.
- This variability contrasts with tighter error bars seen in laboratory animals like mice, which have more controlled genetic backgrounds.
22
Q
What organizations are funding further studies on the new TB vaccine?
A
The Wellcome Trust and the Melinda Gates Foundation are funding larger studies to investigate the new TB vaccine’s efficacy and durability.
23
Q
What is Respiratory Syncytial Virus (RSV) and when is it most common?
A
RSV is a respiratory virus that can cause severe respiratory infections, particularly in children.
It is commonly seen in the winter months and was part of the “quademic” alongside flu, COVID-19, and Norovirus
24
Q
Why has it been difficult to develop a vaccine for RSV?
A
Developing a vaccine for RSV has been challenging due to its complex biology and historical failures in achieving effective and safe immunity.
25
What is the latest advancement in RSV vaccine development?
The FDA has recently approved a new RSV vaccine, marking a significant milestone after years of challenges in RSV vaccine development.
26
Why is the route of vaccination important in mucosal immunology?
The route of vaccination is crucial because mucosal infections occur at mucosal surfaces, which are entry points for about 70% of all infections.
- To generate an effective mucosal immune response, vaccines should target mucosal tissues to prime local dendritic cells.
- This approach helps imprint T cells and B cells with the ability to home back to mucosal sites, offering more localized and effective immunity.
27
What is the difference between systemic and mucosal vaccines?
Systemic vaccines, such as intramuscular or subcutaneous injections, are designed to generate a broad immune response throughout the bloodstream. While they are effective in providing overall protection, they are less capable of inducing mucosal immunity, which is crucial for defending against pathogens that enter through mucosal surfaces.
On the other hand, mucosal vaccines specifically target mucosal membranes, such as the oral or nasal regions. These vaccines excel at activating local immune responses at these frontline tissues, making them particularly effective for protecting against infections that enter the body via these routes.
28
Is mucosal immunization a new concept?
No, the concept of mucosal immunization is not new .scientists were exploring immunity in the gastrointestinal tract in the early 1900s, and Louis Pasteur experimented with oral immunization in the 1800s.
29
Why is mucosal vaccination gaining renewed attention?
It shows potential for protecting against mucosal pathogens, where traditional systemic vaccines have been less effective.
30
Why are mucosal vaccines effective against mucosal pathogens?
They prime local mucosal tissues, enhancing immune surveillance where the pathogen enters.
31
What type of local antibodies do mucosal vaccines induce?
They induce local IgA antibodies, which provide targeted protection at mucosal surfaces.
32
How do mucosal vaccines enhance T cell responses?
They stimulate mucosal T cell responses that help control infections at the site of pathogen entry
33
Why consider mucosal vaccines if systemic vaccines work well?
Systemic vaccines are less effective against certain mucosal pathogens e.g. HIV and TB, where mucosal vaccines may provide better protection
34
What is the main antibody produced in systemic immunity
Systemic immunity mainly induces IgG which is predominantly found in the blood
35
What is the main antibody in mucosal immunity
Mucosal immunity primarly induces IgA, which protects mucosal surfaces
36
Do mucosal compartments produce IgG
Yes, IgG is also present, but IgA is the predominant antibody in mucosal compartments
37
Why is infection prevention important in systemic vaccination
if systemic vaccine doesn't prevent infection, it may not stop the shedding of the pathogen from mucosal surfaces
38
What is a key consideration for mucosal vaccination
It's important to determine if a mucosal vaccine can also induce a sufficient systemic immune response if the pathogen spreads beyond the mucosal tissue
39
when does systemic immunisation vs mucosal immunisation act
systemic immunisation resolves the infection once the virus has spread from a mucosal site whilst the mucosal immunisation prevents the uptae of the virus into mucosal tissues therefore reducing local replication
40
Have there been successful mucosal vaccines in the past?
Yes, the oral polio vaccine is a successful example of a mucosal vaccine.
41
How was the oral polio vaccine administered in the past?
It was given on a sugar cube, but it is now typically administered as a drop `
42
What serotypes does the oral polio vaccine protect against
It protects against serotypes 1,2 and 3
43
What are iron lungs
Iron lungs were devices used to help polio patients breathe when paralysis affected their respiratory muscles
44
How did iron lungs work
They used alternating positive and negative pressure to expand and contract the chest, allowing patients to breathe.
45
Why were iron lungs widely used in the 1950s?
Polio often caused paralysis of the respiratory muscles, making iron lungs essential for patients' survival
46
how do antibdoies made against polio protect people (vaccine)
antibodies protect mucosa against spread to the nervous system
47
How widespread was polio in 1988?
In 1988, polio was widespread across many regions of the world.
48
Where is polio still found today?
Wild type poliovirus type 1 (WPV1) is now limited to a few countries, such as Afghanistan and Pakistan (where the vaccine have been hard to administer)
49
How close are we to eradicating polio?
Polio cases have been reduced by 99.99%, and global eradication is within reach with continued vaccination efforts. in 1988, two of the three wild poliovirus serotypes ( 2 and 3) were eradicated
50
What challenge remains in eradicating polio?
The main challenge is reaching populations in difficult-to-access areas to maintain high vaccination levels.
51
How does the polio virus cause infection?
The polio virus is ingested and enters the body via the fecal-oral route. It binds to receptors on intestinal epithelial cells, called enterocytes, and replicates inside these cells.
52
What happens after the polio virus replicates in the intestines?
After replication, the virus bursts from the intestinal cells and spreads through the body, eventually reaching the central nervous system.
53
How does the oral polio vaccine work?
The oral polio vaccine is a live, attenuated virus that replicates in the intestines. It induces a mucosal immune response, bringing T and B cells to the gut to fight the virus and protect against future infections.
54
What is the potential issue with the oral polio vaccine?
The live virus in the oral polio vaccine can mutate back into a virulent form, potentially causing vaccine-associated paralytic polio in rare cases.
55
How often did vaccine-associated paralytic polio occur with the oral vaccine?
Vacine - associated paralytic polio occured in ~ 1 in 2.7 million doses of the oral vaccine
56
Why was the oral polio vaccine considered beneficial despite its risks?
The risk of vaccine-associated paralytic polio was outweighed by the high rates of polio infections in society at the time.
57
Why was there a shift towards the injectable polio vaccine?
With polio becoming rare, the risk of the oral vaccine became less justified, prompting a shift to the injectable polio vaccine.
58
How does the injectable polio vaccine differ from the oral vaccine
The injectable polio vaccine does not protect the gut so indivu
59
What is significant about smallpox?
Smallpox had a mortality rate of about 35% and has been eradicated through vaccination.
60
Who is known for the smallpox vaccine?
Edward Jenner
61
Who was Edward Jenner (story of vaccination)
Jenner was an English physician who noticed that milkmaids who had cowpox didn't get smallpox. He then tested his theory by inoculating an 8-year-old boy with cowpox matter. The boy developed a local reaction but made a full recovery. Jenner published his findings in 1796
62
Who and when did Edward Jenner first immunise with the smallpox vaccine
Edward jenner immunised a young boy named James Phipps on May 14th 1796
63
What material did Edward Jenner use for the first smallpox vaccination?
He used pus from Sarah Nelms, who had cowpox from a cow named Blossom.
64
Why is Edward Jenner important in medical history?
Edward Jenner is considered the forefather of modern vaccinology and immunology.
65
Where does the term "vaccine" come from?
The term "vaccine" comes from the Latin word "vaca," meaning cow, in honor of Jenner's work with cowpox.
66
Who coined the term "vaccine"?
Louis Pasteur coined the term "vaccine" in honor of Edward Jenner.
67
Was Edward Jenner the first to use vaccination techniques?
No, protective techniques against infection were used for hundreds of years before Jenner e.g in China in the 15th century
68
How did people in ancient China attempt to protect against smallpox?
They used an instrument to blow ground-up smallpox scabs into the nose of a child.
69
What was the risk of the ancient Chinese smallpox protection method?
If the scabs contained a high amount of viable virus, the person could become seriously ill.
70
What are the challenges of delivering mucosal vaccines through the oral route?
The challenges include acidic pH of the gut, mucus layers, physical barriers, and commensal microbes that degrade antigens.
71
Why are mucosal vaccines less common?
Mucosal vaccines face significant barriers like digestive enzymes and the gut's natural resistance to immune activation.
72
What makes a good mucosal vaccine?
A good mucosal vaccine must overcome gut barriers and generate a protective immune response without causing harmful inflammation.
73
Why is inflammation in the gut undesirable?
Inflammation reduces nutrient absorption, which can negatively impact nutrition in the body. this is why the gut has some barriers to immune responses
74
How do protein antigen vaccines enhance uptake at mucosal sites?
Protein antigens are encapsulated in liposomes or nanoparticles to enhance protection and uptake by M cells and enterocytes.
75
What is the role of adjuvants in mucosal vaccines?
Adjuvants target immune cells and enhance trafficking and immune responses.
76
How do whole cell vaccines work at mucosal sites
Whole cell vaccines can include live attenuated or inactivated pathogens that stimulate immune cells after uptake by M cells and enterocytes.
77
What is the benefit of using viral vector vaccines at mucosal sites?
Viral vectors deliver nucleic acid cargo, leading to enhanced protection, uptake, and targeted immune responses.
78
What is the purpose of encapsulation in mucosal vaccines?
Encapsulation protects antigens from degradation and improves uptake and immune cell targeting.
79
What is the role of dendritic cells in mucosal vaccination?
Dendritic cells process antigens and activate adaptive immune responses by mobilizing effector cells to infection sites.
80
Why is formulation important in mucosal vaccines?
Optimum formulation ensures effective delivery, antigen targeting, and activation of antigen-presenting cells, enhancing immune response through trafficking of antigens to the draining lymph nodes and activation, expansion and mobilisation of adaptive immune cells to effector sites
81
What is a benefit of mucosal vaccination
mucosal vaccination recruits immune cells to the site, providing protection and elicinting protective antibodies like IgA
82
What is the function of IgA in the gut lumen?
IgA neutralises viruses and bacteria by being transported across the epithelium into the gut lumen
83
How does IgA handle pathogens trying to cross the epithelium
IgA binds to pathogens attempting to cross the epithelium and can shuttle them back out into the lumen
84
What is the role of IgA in inhibiting adherence?
IgA prevents microbes from adhering to mucosal epithelial cells, reducing infection risk
85
How does mucus trapping work in IgA defense?
IgA binds to mucins, trapping IgA-bound microbes in the mucus layer to prevent adherence.
86
What is the function of IgA in pathogen or toxin neutralization?
IgA binds to receptors or toxins, preventing pathogen internalization and toxin entry.
87
How does IgA contribute to pathogen transport?
IgA binds pathogens and mediates their transport back out of the cell or mucosa via the pIgR.
88
What is immunological tolerance?
It is an acquired mechanism where prior exposure to an antigen reduces the immune response to that antigen upon subsequent exposure.
89
How does tolerance relate to allergy prevention
Tolerance protects against allergy induction such as eczema, hay fever, asthma and food allergies
90
How is mucosal tolerance different in adults?
In adults, the mucosal immune system is mainly geared towards tolerance, avoiding unnecessary responses to foreign antigens unless needed
91
Why is tolerance a challenge for mucosal vaccines
Mucosal vaccines risk inducing tolerance to the vaccine antigen, potentially preventing an effective immune response
92
What is a conern when administering oral vaccines
There is a risk of inducing immune responses against co - ingested substances e.g. food, leading to unintended allergies
93
What type of immunity do animals develop after recovering from a mucosal infection?
They generally develop solid immunity against homologous re-challenge, protecting them from reinfection by a similar strain of the pathogen.
94
What does homologous re challenge mean
It refers to being exposed again to a similar strain of a virus, bacteria or pathogen that the immune system has previously encountered
95
How does feeding on proteins affect immune responses?
Consuming proteins can lead to immunological tolerance to those proteins preventing unnecessary immune responses
96
Why are danger signals or activation signals important in vaccine design
They help trigger immune responses by signalling the presence of a threat preventing tolerance to the vaccine antigen
97
What are Toll-like receptors (TLRs)?
They are evolutionarily conserved pattern recognition receptors that bind to pathogen-associated molecular patterns (PAMPs), which are essential structures on viruses and bacteria.
98
Why might live vaccines elicit stronger immune responses than protein-based vaccines?
Live vaccines involve viral replication, amplifying antigens and generating danger signals, which enhance antibody and T cell responses.
99
What are the advantages of live vaccines?
They cause viral replication, antigen amplification, cell death, and danger signals, providing inherent adjuvant properties that strengthen immune responses.
100
What are some novel adjuvants and delivery vehicles being explored for vaccines?
Attenuated Salmonella, cholera-like enterotoxins, ISCOMS, nanoparticle formulations, and viral vectors are being developed to enhance vaccine efficacy.
101
Why is the site of antigen uptake important in vaccine design?
The site affects the immune outcome; Peyer's patch immunization induces active immunity, while uptake across villus epithelium promotes tolerance.
102
What are examples of bacteria used as vaccine vectors?
Mycobacteria, Vibrio cholerae, Listeria, Shigella, and Salmonella are used to deliver antigens and stimulate immune responses.
103
What are examples of viruses used as vaccine vectors?
Adenoviruses, poxviruses (e.g., MVA), and VSV are used to deliver genetic material, causing endogenous expression of vaccine antigens.
104
Why is it important to consider the location of vaccine uptake in the gastrointestinal tract?
Different sites may induce different immune responses, impacting the efficacy and safety of the vaccine.
105
What type of bacterium is Salmonella?
Salmonella is a rod-shaped, gram-negative, facultative anaerobe belonging to the Enterobacteriaceae family.
106
Which strains of Salmonella are used as vaccine vectors?
Attenuated strains of Salmonella Typhi (S. Typhi) and Salmonella Typhimurium (S. Typhimurium) are commonly used.
107
Why is Salmonella an effective vaccine vector?
It naturally infects through mucosal surfaces, mimicking many mucosal pathogens which help induce a strong immune response
108
How does Salmonella enhance immune responses as a vacine vector
It is an intracellular pathogen that survives and replicates within antigen presenting cells, continuously processing ad presenting foreign antigens
109
What is a key advantage of using Salmonella for vaccine production?
It is relatively inexpensive to produce, making it suitable for large-scale mass immunizations.
110
Why is Salmonella considered safe for use in humans as a vaccine vector?
It can be irreversibly attenuated, meaning it is modified to be non-virulent and has a better safety profile compared to viruses.
111
How can adverse reactions to Salmonella-based vaccines be managed?
They can be easily treated with antibiotics if adverse reactions occur.
112
What is an advantage of delivering Salmonella-based vaccines orally?
Oral delivery improves compliance, especially among children, as it is more practical and socially acceptable than injections.
113
Why is Salmonella suitable for delivering multiple antigens?
It can carry large amounts of foreign DNA (large multivalent antigen capacity), enabling the delivery of one or more foreign antigens.
114
How does Salmonella’s ability to avoid rapid immune clearance enhance its effectiveness as a vaccine vector?
It hides within cells, allowing prolonged antigen presentation, which helps generate a stronger immune response.
115
What type of virus is an adenovirus?
Adenovirus is a nonenveloped icosahedral virus with a double-stranded DNA genome, about 70-90 nm in size.
116
What is the structure of an adenovirus?
It has an outer protein shell surrounding an inner nucleoprotein core, with penton fibers extending from its apexes.
117
Why is the adenovirus genome suitable for vaccine development?
Its genome is 34-43 kb, making it easy to manipulate for genetic modifications.
118
What makes adenoviruses versatile as vaccine vectors?
They can infect a wide range of mammalian cells, including both dividing and quiescent cells.
119
How is transgene expression enhanced in adenovirus vectors?
It is robust and can be further enhanced using strong heterologous promoters.
120
Why are adenoviruses considered safe as vaccine vectors?
Their genome remains mostly epichromosomal and does not integrate into the host chromosome, minimizing the risk of insertional mutagenesis.
121
How can adenovirus vectors be administered?
They can be administered via parenteral routes (subcutaneous, intravenous, intramuscular, or intraperitoneal) and mucosal routes (oral or intranasal).
122
What is an advantage of adenovirus replication in vaccine delivery?
Replication amplifies the amount of vaccine antigen generated, enhancing immune responses.
123
What type of immune response do adenovirus vectors induce?
They induce strong antibody and T-cell immune responses.They induce strong antibody and T-cell immune responses.
124
Why is the production of adenovirus vectors advantageous for large-scale vaccination?
They can be easily grown on a large scale in tissue culture, making production relatively simple)
125
What are the advantages of using adenovirus vectors as vaccines?
Adenovirus vectors can infect a wide range of mammalian cells, including dividing and quiescent cells. They provide robust transgene expression, which can be enhanced by strong heterologous promoters. Their production is simple, as they can be grown on a large scale in tissue culture. The vector genome remains epichromosomal, avoiding risks of insertional mutagenesis. Additionally, they induce strong immunity when administered via parenteral or mucosal routes.
126
What are attenuated viral vectors used for in vaccines?
They are used to deliver wreaked viruses that stimulate an immune response without causing disease e.g. rabies, influenza and polio
127
How is the attenuated rabies vaccine administered to wild animals?
he vaccine was placed into bait and distributed in areas with rabies concerns, such as the countryside, to vaccinate wild fox populations.
128
What is a drawback of the attenuated rabies vaccine?
The attenuation is not always stable, which is why recombinant vaccines based on poxvirus and adenovirus vectors are now preferred.
129
ow does the live attenuated influenza vaccine (LAIV) work?
It is designed to replicate at a temperature lower than the body’s core temperature, leading to limited replication but strong mucosal immunity.
130
How is the live attenuated influenza vaccine administered?
It is given as a nasal spray (e.g., FluMist Quadrivalent).
131
How is poliovirus attenuated for vaccine use?
Mutations in the capsid protein gene and non-coding regions prevent viral RNA translation in the central nervous system (CNS), making it safer for vaccination.
132
Why are adenoviral vectors effective for vaccine delivery?
They can infect a wide range of cells, deliver genetic sequences that replicate to amplify antigen production, and induce strong systemic and mucosal immune responses.
133
What are the advantages of viral vector-based vaccines?
They generate strong antibody and T-cell responses and can be applied both systemically and mucosally.
134
What are non-living delivery systems used in vaccines?
- Microparticles and nanoparticles (e.g., polylactides and polylactides-co-glycolides)
- Liposomes (phospholipid vesicles that can entrap antigens or present them on the surface)
- DNA vaccines (delivered via a gene gun for needle-free injection)
- Transgenic plants (e.g., ‘Mucorice’) that produce vaccines and can be consumed for mucosal immunity.
135
How do liposomes function in vaccine delivery?
They are phospholipid vesicles that can trap antigens inside an aqueous core or present them on their surface, mimicking viruses to enhance immune responses.
136
What is the concept behind transgenic plants as vaccines
Genetically modified plants can produce vaccine antigens, and consuming them may trigger an immune response.
137
What is the advantage of using transgenic plants in vaccine development?
They allow large-scale vaccine production and can induce immunity when consumed, providing a practical and cost-effective vaccination method.
138
What is mucosal linkage in mucosal vaccines?
Mucosal linkage refers to the phenomenon where priming one mucosal surface can generate an immune response at a different mucosal surface.
139
What type of immune response does oral immunization generate?
Oral immunization generates a mucosal immune response in the gastrointestinal tract and also in breast milk.
140
ow does nasal immunization affect immune responses?
Nasal immunization produces immune responses in the lungs and respiratory tract, as well as in the genital urinary tract, but not in the gut.
141
Does vaginal immunization provide immune responses to the respiratory tract?
No, vaginal immunization does not generate immune responses in the nasal or respiratory mucosa.
142
How might mucosal vaccines be used in developing an AIDS vaccine?
A nasal delivery method could be used to generate immune responses in the genital urinary tract.
143
What is cholera and what causes it?
Cholera is a disease caused by Vibrio cholerae, leading to severe dehydration from diarrhea and hypovolaemic shock which can be fatal if untreated
144
what is the stool output in severe cases of cholera
stool output can be as high as 1000 mL/h in adults and 10–20 cm3/kg per h in children.
145
How does Vibrio cholerae cause severe diarrhea?
The cholera toxin disrupts the intestine’s ability to absorb liquids and increases water and bicarbonate secretion, leading to profuse watery diarrhea.
146
What are the two parts of the cholera toxin and their functions?
The A subunit is the active enzyme, and the B subunit binds to intestinal epithelial cells.
147
What is the infectious dose of Vibrio cholerae?
Typically, around 100 million bacteria, but this can be lower depending on conditions.
148
How long does natural infection with Vibrio cholerae provide protection?
Human challenge studies show high protection for 3+ years after infection with the same serogroup.
149
What is the incubation perioid of cholera
usually between half a day and 4.5 days (median 1.4 days) after illness typically starts suddenly with fequent stool passage and often vomiting
150
What is the role of IgA in cholera protection?
IgA is a key mediator of immunity against cholera, neutralizing the pathogen and its toxin.
151
What are the types of oral cholera vaccines available?
1. killed whole-cell vaccines (Shanchol, Shantha Biotechnics, Hyderabad, India; and Euvichol, Eubiologics, Gangwon-do, South Korea),
2. killed whole cell vaccine with a recombinant B subunit (Dukoral, Valneva, Sweden),
3. live attenuated vaccine (Vaxchora, Emergent Biosolutions, Rockville, MA, USA; table).
152
How long do killed whole-cell vaccines provide protection against cholera?
At least 5 years
153
Is cholera immunity serogroup-specific?
Yes, protection is serogroup-specific, and cross-protection between O1 serotypes (Ogawa and Inaba) is incomplete and asymmetric.
154
How do cholera vaccines work?
They elicit B cells that secrete IgA, which binds to and neutralizes Vibrio cholerae.
155
What role does innate immunity play in cholera protection?
It helps control V. cholerae at the mucosal surface and initiates adaptive immunity through a broad inflammatory response.
156
What immune cells are involved in the innate response to cholera infection?
Macrophages and neutrophils.
157
What is the primary adaptive immune response against Vibrio cholerae?
It targets V. cholerae lipopolysaccharide O-antigen and cholera toxin.
158
What are the key antibodies involved in cholera immunity and their functions?
- Anti-O-antigen antibodies: Inhibit colonization and motility.
- Anti-cholera toxin antibodies: Block receptor binding.
- Vibriocidal antibodies: Indirect markers of mucosal immunity, correlating with protection but lacking a definitive protective titer.
159
What are some considerations for future vaccine development?
Whether to continue systemic vaccines or develop mucosal vaccines for diseases like SARS-CoV-2, HIV-1, influenza, and TB.
