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Salmonella Vaccines
Plan of Talk
 Aim of Salmonella vaccination
 Characteristics of an ideal Salmonella vaccine
 Types of salmonella vaccin...
Plan of Talk
 Aim of Salmonella vaccination
 Characteristics of an ideal Salmonella vaccine
 Types of salmonella vaccin...
Aim of Salmonella Vaccination
The aim of vaccination as part of a complex control programs for
Salmonella infections in po...
Plan of Talk
 Aim of Salmonella vaccination
 Characteristics of an ideal Salmonella vaccine
 Types of salmonella vaccin...
Ideal Salmonella Vaccine Strain
1. High degree of protection against systemic and intestinal
infection.
2. High protective...
Cont. …
6. Vaccines should be easy to administer and need to have
markers enabling the differentiation from salmonella wil...
Cont. …
10. Salmonella vaccine strains should have preserved the ability
to invade the gut as prerequisite to induce the i...
Plan of Talk
 Aim of Salmonella vaccination
 Characteristics of an ideal Salmonella vaccine
 Types of salmonella vaccin...
Live Virus Attenuation
The aim of attenuation is to diminish the virulence of the
pathogen, but retaining its immunogenici...
Live Attenuated Vaccines
Risk Factors
Several risks are associated with live vaccines, especially in
immunocompromised ind...
Cont. …
Under these points of view, despite their extended use, the
restrictions for the use of attenuated modified organi...
Live Attenuated Vaccines
Advantages Over Inactivated Ones
1. Easy administration.
2. Ability to carry heterologous antigen...
Live Attenuated Vaccines
Empirical Attenuation
Methods
Attenuated Mutations
Metabolic functions
Virulence factors
Methods ...
Live Attenuated Vaccines
Empirical Attenuation
Methods
Attenuated Mutations
Metabolic functions
Virulence factors
Live Attenuated Vaccines
Empirical Attenuation Methods
The empirical attenuation methods developed by Pasteur and
Koch at ...
Live Attenuated Vaccines
Empirical Attenuation
Methods
Attenuated Mutations
Metabolic functions
Virulence factors
Live Attenuated Vaccines
Empirical Attenuation
Methods
Attenuated Mutations
Metabolic functions
Virulence factors
Live Attenuated Vaccines
Attenuated Mutations
The knowledge we have nowadays about genomics allows us to
selectively knock...
Cont. …
Salmonella has around 4,500 genes.
A change in any gene (mutation) can lead to an alteration in
protein.
This muta...
Target Mutagenesis
Specific alteration by genetic manipulation of the genome;
Insertion, deletion or framshift changes al...
Deletion
 A gene or part of it is knocked out.
 The gene is no longer transcribed, no
RNA and no protein is synthesized....
Insertion
 A foreign piece of DNA is inserted into
the targeted gene.
 This knocks out the gene function
although transc...
Live Attenuated Vaccines
Attenuated Mutations
Advantages of this strategy:
1. Some important antigenic determinants can be...
Live Attenuated Vaccines
Empirical Attenuation
Methods
Attenuated Mutations
Metabolic functions
Virulence factors
Live Attenuated Vaccines
Attenuated Mutations/Metabolic Functions
The most widely studied metabolically attenuated strains...
Cont. …
In general, auxotrophy can interfere with bacterial replication
within the host whenever the required metabolites ...
Live Attenuated Vaccines
Empirical Attenuation
Methods
Attenuated Mutations
Metabolic functions
Virulence factors
Live Attenuated Vaccines
Attenuated Mutations/Virulence Factor
 The two more extensively characterized virulence-attenuat...
Plan of Talk
 Aim of Salmonella vaccination
 Characteristics of an ideal Salmonella vaccine
 Types of salmonella vaccin...
Killed Whole Organisms
 To avoid the risk of live vaccines, the use of killed organisms
was introduced as safer vaccines....
Cont. …
 However, protection induced by bacterins in poultry is
generally modest .
 The limitations of these kinds of va...
Plan of Talk
 Aim of Salmonella vaccination
 Characteristics of an ideal Salmonella vaccine
 Types of salmonella vaccin...
Subunit Vaccines
Subunit vaccines contain immunodominant components of the
bacteria.
Subunit vaccines may be:
1. Crude or ...
Cont. …
The primary goal of this approach is:
1. To identify the individual antigens of the pathogen that
are involved in ...
Cont. …
Combining genomics with our understanding of pathogenesis, it
is possible to identify specific proteins from most ...
Cont. …
The potential advantages are;
1. Vaccine safety.
2. The potential abilities to target the vaccines to the site
whe...
Cont. …
 In spite of these data, low levels of resistance against
salmonellosis can be induced by administration of flage...
Cont. …
 New generation adjuvants are designed to induce minimal
side effects, enhance the duration of the immune respons...
Ideal vaccine
properties
Attenuated Inactivated
Subunit
Classical
Adjuvant (Alum)
New adjuvants
(DDS)
I +++ + + +++
II +++...
I
A good vaccine should stimulate a strong, protective and long
lasting immune response. Through the induction of strong, ...
II
A good vaccine should induce the right sort of immune
responses.
The protective immune responses against extracellular
...
III
An ideal vaccine should be safe.
Despite the success of vaccination in eliminating disease and
death, the public accep...
IV
A single dose of vaccine should confer robust, long-lived
immunity.
Only a few live vaccines have achieved this goal. I...
V
An ideal vaccine should be affordable by the population at which
they are aimed and should be formulated to resist high ...
Plan of Talk
 Aim of Salmonella vaccination
 Characteristics of an ideal Salmonella vaccine
 Types of salmonella vaccin...
Immunoadjuvants
Adjuvants
They are defined as a group of structurally heterogenous
compounds that enhance or modulate the ...
Cont. …
 Despite the recognition of many
different types of adjuvant, however,
little is known about their mode of
action...
Cont. …
The events triggered by these immunomodulators appear to
come from one or the combination of several of the follow...
Immunoadjuvants Effects
Adjuvant Effect
Depot Effect
Effect On Antigen
Presenting Cells (APC)
Nonspecific
Immunostimulanti...
Immunoadjuvants
Depot Effect
If antigen is present in
a solution, it is mostly
quickly removed by
neutrophils and
macropha...
Immunoadjuvants
Depot Effect
Adjuvants, such as:
1. Oil emulsions
2. Antigen absorbing aluminium salts
Retain antigen at t...
Immunoadjuvants
Depot Effect
 In the case of use of alum, the mechanism of action seems to
be due to
 Formation of a dep...
Immunoadjuvants Effects
Adjuvant Effect
Depot Effect
Effect On Antigen
Presenting Cells (APC)
Nonspecific
Immunostimulanti...
Immunoadjuvants
Effect On Antigen Presenting Cells (APC)
The adjuvant induced enhancement of an immune response may
be rel...
Immunoadjuvants
Effect On Antigen Presenting Cells (APC)
This results in:
1. Increase in the provision of antigen-loaded A...
Immunoadjuvants Effects
Adjuvant Effect
Depot Effect
Effect On Antigen
Presenting Cells (APC)
Nonspecific
Immunostimulanti...
Immunoadjuvants
Nonspecific Immunostimulating Effect
 Some agents can stimulate the non-specific component of the
immune ...
Immunoadjuvants
Nonspecific Immunostimulating Effect
Some examples are:
1. Lipopolisaccharide (LPS)
2. Monophosphoryl lipi...
Immunoadjuvants Effects
Adjuvant Effect
Depot Effect
Effect On Antigen
Presenting Cells
(APC)
Nonspecific
Immunostimulanti...
Immunoadjuvants
Particulated Carrier Systems
 Particulated Carrier Systems have been proposed to improve
the mucosal bioa...
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Salmonella in poultry_vaccination

"عسى أن تكون علما ينتفع به"
Salmonella vaccine
Salmonella Entritidis
Typhoid

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Salmonella in poultry_vaccination

  1. 1. Salmonella Vaccines
  2. 2. Plan of Talk  Aim of Salmonella vaccination  Characteristics of an ideal Salmonella vaccine  Types of salmonella vaccines – Live attenuated – Inactivated – Subunit  Immunoadjuvants
  3. 3. Plan of Talk  Aim of Salmonella vaccination  Characteristics of an ideal Salmonella vaccine  Types of salmonella vaccines – Live attenuated – Inactivated – Subunit  Immunoadjuvants
  4. 4. Aim of Salmonella Vaccination The aim of vaccination as part of a complex control programs for Salmonella infections in poultry is to: 1. Reduce or prevent the intestinal colonization resulting in reduced fecal shedding and egg shell contamination. 2. Prevent systemic infection resulting in a diminished localization in the reproductive tissues.
  5. 5. Plan of Talk  Aim of Salmonella vaccination  Characteristics of an ideal Salmonella vaccine  Types of salmonella vaccines – Live attenuated – Inactivated – Subunit  Immunoadjuvants
  6. 6. Ideal Salmonella Vaccine Strain 1. High degree of protection against systemic and intestinal infection. 2. High protective potential against a variety of important serovars (serogroups) 3. Adequate attenuation for poultry, other animal species, humans and the environment. 4. Inactivated and live vaccines should not affect growth of the animal. 5. Vaccine strains should not be resistant to antibiotics.
  7. 7. Cont. … 6. Vaccines should be easy to administer and need to have markers enabling the differentiation from salmonella wild- type strains. 7. Application of vaccines should not interfere with salmonella detection methods. 8. Humoral antibody response after vaccination should be distinguishably from a salmonella wild-type response to allow the use of serological detection methods 9. Attenuated live salmonella vaccine strains should be able to induce the colonisation inhibition effect between salmonella organisms.
  8. 8. Cont. … 10. Salmonella vaccine strains should have preserved the ability to invade the gut as prerequisite to induce the invasion inhibition effect between salmonella organisms
  9. 9. Plan of Talk  Aim of Salmonella vaccination  Characteristics of an ideal Salmonella vaccine  Types of salmonella vaccines – Live attenuated – Inactivated – Subunit  Immunoadjuvants
  10. 10. Live Virus Attenuation The aim of attenuation is to diminish the virulence of the pathogen, but retaining its immunogenicity.
  11. 11. Live Attenuated Vaccines Risk Factors Several risks are associated with live vaccines, especially in immunocompromised individuals: 1. Some of the structural components of the microorganism used may contain immunosuppressive antigens. 2. Attenuated strains may still have some residual virulence due to an incomplete inactivation. 3. Attenuated strains, after being released into the environment, can recover their virulence in other hosts, or can acquire genes from other microorganisms by natural genetic transfer.
  12. 12. Cont. … Under these points of view, despite their extended use, the restrictions for the use of attenuated modified organisms in vaccination are becoming more and more stringent.
  13. 13. Live Attenuated Vaccines Advantages Over Inactivated Ones 1. Easy administration. 2. Ability to carry heterologous antigens. 3. Capacity to induce cellular and humoral immune responses.
  14. 14. Live Attenuated Vaccines Empirical Attenuation Methods Attenuated Mutations Metabolic functions Virulence factors Methods of Attenuation
  15. 15. Live Attenuated Vaccines Empirical Attenuation Methods Attenuated Mutations Metabolic functions Virulence factors
  16. 16. Live Attenuated Vaccines Empirical Attenuation Methods The empirical attenuation methods developed by Pasteur and Koch at the end of the twentieth century. Many successful live viral and bacterial vaccines are produced by repetitive in vitro passage in cell culture.
  17. 17. Live Attenuated Vaccines Empirical Attenuation Methods Attenuated Mutations Metabolic functions Virulence factors
  18. 18. Live Attenuated Vaccines Empirical Attenuation Methods Attenuated Mutations Metabolic functions Virulence factors
  19. 19. Live Attenuated Vaccines Attenuated Mutations The knowledge we have nowadays about genomics allows us to selectively knock out concrete virulence genes.
  20. 20. Cont. … Salmonella has around 4,500 genes. A change in any gene (mutation) can lead to an alteration in protein. This mutation may change the structure and function of the bacterium. Some mutation may have no effect.
  21. 21. Target Mutagenesis Specific alteration by genetic manipulation of the genome; Insertion, deletion or framshift changes alter the gene structure or function. Deletion and insertion frequently used experimentally and in potential vaccines.
  22. 22. Deletion  A gene or part of it is knocked out.  The gene is no longer transcribed, no RNA and no protein is synthesized. A B C A C
  23. 23. Insertion  A foreign piece of DNA is inserted into the targeted gene.  This knocks out the gene function although transcribed RNA no longer encodes correct protein.  Here gene B in an inserted.  Insertions are less stable than deletions, but easier to perform. A C A CB
  24. 24. Live Attenuated Vaccines Attenuated Mutations Advantages of this strategy: 1. Some important antigenic determinants can be retained by attenuated strains that are able to elicit both antibody and cellular immunity. 2. Growing capacity of these attenuated vaccines provides prolonged exposure of antigens to the immune system, resulting in the production of long-lasting memory cells.
  25. 25. Live Attenuated Vaccines Empirical Attenuation Methods Attenuated Mutations Metabolic functions Virulence factors
  26. 26. Live Attenuated Vaccines Attenuated Mutations/Metabolic Functions The most widely studied metabolically attenuated strains include mutants deficient in: The biosynthesis of: 1. Aromatic amino acids (i.e. aroA, or aroC and aroD) 2. Purines (purA, purE) Or in the production of: 1. Adenylate cyclase (cya) 2. Cyclic AMP receptor protein (crp).
  27. 27. Cont. … In general, auxotrophy can interfere with bacterial replication within the host whenever the required metabolites are: 1. Absent. 2. Present in amounts insufficient for bacterial growth in the compartment where the bacteria reside.
  28. 28. Live Attenuated Vaccines Empirical Attenuation Methods Attenuated Mutations Metabolic functions Virulence factors
  29. 29. Live Attenuated Vaccines Attenuated Mutations/Virulence Factor  The two more extensively characterized virulence-attenuated vaccine strains have mutations in the two-component regulatory system phoP/phoQ or in Salmonella pathogenicity island 2 (SPI2) loci.
  30. 30. Plan of Talk  Aim of Salmonella vaccination  Characteristics of an ideal Salmonella vaccine  Types of salmonella vaccines – Live attenuated – Inactivated – Subunit  Immunoadjuvants
  31. 31. Killed Whole Organisms  To avoid the risk of live vaccines, the use of killed organisms was introduced as safer vaccines.  These vaccines are made from the entire organism but inactivated (killed) by physical or chemical agents.
  32. 32. Cont. …  However, protection induced by bacterins in poultry is generally modest .  The limitations of these kinds of vaccines are: 1. Their immunogenicity usually has to be enhanced by co- administration with adjuvants. 2. Multiple doses are necessary for obtaining long-term protective immunity; besides, as live vaccines, they may contain immunosuppressive antigens.
  33. 33. Plan of Talk  Aim of Salmonella vaccination  Characteristics of an ideal Salmonella vaccine  Types of salmonella vaccines – Live attenuated – Inactivated – Subunit  Immunoadjuvants
  34. 34. Subunit Vaccines Subunit vaccines contain immunodominant components of the bacteria. Subunit vaccines may be: 1. Crude or purified extracts of the pathogen. 2. Synthetic peptides. 3. Obtained by the use of recombinant DNA technology, pure DNA or RNA.
  35. 35. Cont. … The primary goal of this approach is: 1. To identify the individual antigens of the pathogen that are involved in inducing protection. 2. Avoiding the immunosuppressive ones.
  36. 36. Cont. … Combining genomics with our understanding of pathogenesis, it is possible to identify specific proteins from most pathogens that are critical in inducing the right protective immune responses.
  37. 37. Cont. … The potential advantages are; 1. Vaccine safety. 2. The potential abilities to target the vaccines to the site where immunity is required. 3. To differentiate vaccinated animals from the infected ones through the right selection of the components.
  38. 38. Cont. …  In spite of these data, low levels of resistance against salmonellosis can be induced by administration of flagella, porins or polysaccharide fractions.  The potency of these vaccines is often poor when administered without adjuvant and/or a delivery system.
  39. 39. Cont. …  New generation adjuvants are designed to induce minimal side effects, enhance the duration of the immune response, and concurrently stimulate humoral and cellular immune responses.
  40. 40. Ideal vaccine properties Attenuated Inactivated Subunit Classical Adjuvant (Alum) New adjuvants (DDS) I +++ + + +++ II +++ + + +++ III + ++ ++ +++ IV + + + +++ V + +++ + +++ Strong, protective and long lasting immune response Right sort of immune responses. Safe Single dose of vaccine should confer robust, long-lived immunity. Affordable
  41. 41. I A good vaccine should stimulate a strong, protective and long lasting immune response. Through the induction of strong, long- lived immunological specific T and B cell memory cells. Measurement of the specific subsets elicited by immunization may guide vaccine development.
  42. 42. II A good vaccine should induce the right sort of immune responses. The protective immune responses against extracellular pathogens seem to be mediated by long-lived humoral immune responses through the production of antibodies. However, in the control of intracellular infection, cellular immune responses have been shown to be crucial in mediating protection. Therefore, the development of a successful vaccine against those diseases will be facilitated by a thorough understanding of how cellular immune responses are generated and maintained in vivo.
  43. 43. III An ideal vaccine should be safe. Despite the success of vaccination in eliminating disease and death, the public acceptance of even minor side effects of vaccination is very low. One major challenge faced in developing new vaccines is to achieve strong immunogenicity without increasing reactogenicity.
  44. 44. IV A single dose of vaccine should confer robust, long-lived immunity. Only a few live vaccines have achieved this goal. In contrast to the results with live vaccines, it has been difficult to promote long lived immunity with a single dose of non-living antigen vaccines. One goal of vaccine development is to rectify this using new adjuvants and antigen delivery systems.
  45. 45. V An ideal vaccine should be affordable by the population at which they are aimed and should be formulated to resist high and low temperatures to facilitate distribution. This is a main problem for alive attenuated vaccines
  46. 46. Plan of Talk  Aim of Salmonella vaccination  Characteristics of an ideal Salmonella vaccine  Types of salmonella vaccines – Live attenuated – Inactivated – Subunit  Immunoadjuvants
  47. 47. Immunoadjuvants Adjuvants They are defined as a group of structurally heterogenous compounds that enhance or modulate the immunogenicity of the associated antigens.
  48. 48. Cont. …  Despite the recognition of many different types of adjuvant, however, little is known about their mode of action.  Janeway called adjuvants “the immunologists dirty little secret”, because their mode of action is poorly understood.
  49. 49. Cont. … The events triggered by these immunomodulators appear to come from one or the combination of several of the following effects:
  50. 50. Immunoadjuvants Effects Adjuvant Effect Depot Effect Effect On Antigen Presenting Cells (APC) Nonspecific Immunostimulanting Effect Particulated Carrier Systems
  51. 51. Immunoadjuvants Depot Effect If antigen is present in a solution, it is mostly quickly removed by neutrophils and macrophages. Subsequently, antigens are unable to prime naive T cells. Following that, the antigens disappear and the immune response is hardly detectable.
  52. 52. Immunoadjuvants Depot Effect Adjuvants, such as: 1. Oil emulsions 2. Antigen absorbing aluminium salts Retain antigen at the injection site, Then, it is released in minute quantities over a prolonged period of time. These compounds mainly stimulate the production of antibodies by the induction of Th2-lymphocytes.
  53. 53. Immunoadjuvants Depot Effect  In the case of use of alum, the mechanism of action seems to be due to  Formation of a depot of free alum that will induce the recruitment and activation of immune cells to the site of inoculation.
  54. 54. Immunoadjuvants Effects Adjuvant Effect Depot Effect Effect On Antigen Presenting Cells (APC) Nonspecific Immunostimulanting Effect Particulated Carrier Systems
  55. 55. Immunoadjuvants Effect On Antigen Presenting Cells (APC) The adjuvant induced enhancement of an immune response may be related to the improved delivery of antigens into the draining lymph nodes. This may be achieved by: 1. Facilitating the antigen uptake by APCs. 2. Increasing the influx of APCs into the injection site.
  56. 56. Immunoadjuvants Effect On Antigen Presenting Cells (APC) This results in: 1. Increase in the provision of antigen-loaded APCs, and in turn, effective priming of specific T cells. 2. Promoting the activation state of APCs by upregulating costimulatory signals or MHC expression. 3. This results in the corresponding cytokine release, enhancing the speed, magnitude and duration of the specific immune response.
  57. 57. Immunoadjuvants Effects Adjuvant Effect Depot Effect Effect On Antigen Presenting Cells (APC) Nonspecific Immunostimulanting Effect Particulated Carrier Systems
  58. 58. Immunoadjuvants Nonspecific Immunostimulating Effect  Some agents can stimulate the non-specific component of the immune system.  Numerous microorganisms contain “alert signals”, the so called “microbial or pathogen associated molecular patterns” (MAMPs or PAMPs, respectively), which is not present in mammalian cells.  These structures activate immune cells through interaction with specific receptors (toll like receptors, TLRs).
  59. 59. Immunoadjuvants Nonspecific Immunostimulating Effect Some examples are: 1. Lipopolisaccharide (LPS) 2. Monophosphoryl lipid A (MPL) 3. Flagellin 4. Lipoproteins 5. Muramil dipeptide (MDP) 6. Trehalose dimycolate (TDM), 7. Cpg DNA, among others. Besides, the special chemical nature of some polymers used in the formulation of vaccine delivery systems may also be recognized as scavenger ligands for the APCs.
  60. 60. Immunoadjuvants Effects Adjuvant Effect Depot Effect Effect On Antigen Presenting Cells (APC) Nonspecific Immunostimulanti ng Effect Particulated Carrier Systems
  61. 61. Immunoadjuvants Particulated Carrier Systems  Particulated Carrier Systems have been proposed to improve the mucosal bioavailability of antigens. These carriers protect labile molecules from degradation in the gastrointestinal tract.  Nanoparticles are submicron-sized colloidal systems that may protect antigen against chemical, enzymatic or immunological degradation, and facilitates targeting and presentation of antigens to inductive sites of mucosal immune system.

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