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VIRUS LIKE
PARTICLES
Abrar Gayas
VB/2011/1075
3rd
YEAR
WHAT?
 VLPs are formed by structural viral
proteins which have an inherent property
for self-assembly, and mimic the
morphology of the pathogen.
 In contrast to live viruses, VLPs are non-
infective and non-replicating, since they
are essentially devoid of infectious
genetic material.
VLPs are often used in studies to identify
protein components required for viral
assembly.
 VLPs are useful tools for the
development of vaccines.
Protein Delivery
WHY TO STUDY VLPs
As Vaccines
 DEVELOPMENT
Over recent years, advances in recombinant DNA
technologies and genetic engineering have led to the
development of subunit vaccines (SUVs)
 SUVs are based on specific components of pathogens,
often located on their surface. Therefore, SUVs are
considered safer than full pathogen-based inactivated
or live attenuated vaccines
 Virus-like particles (VLPs) represent a major
advancement in the development of SUVs with
enhanced immunogenicity.
HOW????
 VLPs display antigenic epitopes in the
correct conformation and in a highly
repetitive manner, leading to cross-
linking of B cell immunoglobulin
receptors and B cell activation
 As exogenous antigens, VLPs are
efficiently taken up by professional
antigen presenting cells, particularly
dendritic cells (DCs),followed by antigen
processing and presentation by MHC class
II molecules
 DC activation and maturation through up-
regulation of co stimulatory molecules and
cytokine production, and stimulation of
CD4+T helper cells, leading to the
induction of strong humoral and cellular
immune responses
 Similar to native viruses, VLPs are
processed in the cytosol of DCs and are
presented by MHC class I molecules to
cytotoxic CD8+T cells by the cross-
presentation mechanism, inducing potent
cytotoxic immune response
 A number of VLP-based vaccine
candidates, including GSK’s anti-
malaria vaccine RTS,S, are in
clinical development while many
others, targeting pathogens such
as influenza virus, rotavirus and
human immunodeficiency virus are
undergoing pre-clinical
evaluation .
i
INFECTIOUS INFLUENZA VIRUS
To date, VLPs, non-enveloped and
enveloped, have been produced for a
number of targets using mammalian,
plant , insect , yeast or bacterial cells
and cell-free platforms
 VLPs formed in yeast or insect larvae are
purified after breaking the cells and
incorporated with fish food pellets
 Alternatively, purified VLPs are encapsulated
and mixed into feed for oral delivery
TYPES
 Non-enveloped VLPs are typically composed of one or
more components of a pathogen with the ability to self-
assemble into particles and do not include any host
components (Fig. 1A).
 This approach has been used to develop vaccines against
such pathogens as HPV and RV . Non-enveloped VLPs
continue to be explored as a preferred approach for
developing SUVs against a number of pathogens, including
canine, mink and porcine parvoviruses using VP2 protein
expressed in insect cells
 In summary, non-enveloped VLPs can consist of a single or
multiple components of a target pathogen or a single or
multiple vaccine target antigens displayed on the VLP
surface as afusion to a heterologous viral protein with the
ability to self-assemble
 Enveloped VLPs are relatively complex structures
consisting of the host cell membrane (an envelope)
with integrated target anti-gens displayed on the outer
surface
 Enveloped VLPs provide a higher degree of flexibility
for integration of more antigens from the same or
heterologous pathogens The most prominent examples
of enveloped VLPs are VLPs engineered to express
vaccine target antigens from influenza viruses
retroviruses and hepatitis C virus (HCV)
 Production of enveloped VLPs requires co-expression
of several structural viral proteins, their assembly
into particles, incorporation into host membranes
and release of particles (budding) from the cell
membrane
For example, a successful assembly and bud-ding of
influenza A/Udorn/72 (H3N2) VLPs have been
achieved by co-expressing four structural proteins
(hemagglutinin [HA], neuraminidase [NA], matrix
protein M1 and ion channel protein M2) of the
virus.
In conclusion, enveloped VLPs represent complex
structures consisting of multiple components of
target pathogens and host membrane components
and resemble the pathogen
As Protein Delivery:
Cell Culture Transfection
Using Three Components:
1. Protein(Thereupetic Drug)
2. Structural Protein Isolated From Virus
3. Surface Proteins Dotted With Glycoproteins
Used In Prostate Cancer
Thank you
Virus Like Particles

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Virus Like Particles

  • 2. WHAT?  VLPs are formed by structural viral proteins which have an inherent property for self-assembly, and mimic the morphology of the pathogen.  In contrast to live viruses, VLPs are non- infective and non-replicating, since they are essentially devoid of infectious genetic material.
  • 3.
  • 4.
  • 5. VLPs are often used in studies to identify protein components required for viral assembly.  VLPs are useful tools for the development of vaccines. Protein Delivery WHY TO STUDY VLPs
  • 6. As Vaccines  DEVELOPMENT Over recent years, advances in recombinant DNA technologies and genetic engineering have led to the development of subunit vaccines (SUVs)  SUVs are based on specific components of pathogens, often located on their surface. Therefore, SUVs are considered safer than full pathogen-based inactivated or live attenuated vaccines  Virus-like particles (VLPs) represent a major advancement in the development of SUVs with enhanced immunogenicity.
  • 7. HOW????  VLPs display antigenic epitopes in the correct conformation and in a highly repetitive manner, leading to cross- linking of B cell immunoglobulin receptors and B cell activation  As exogenous antigens, VLPs are efficiently taken up by professional antigen presenting cells, particularly dendritic cells (DCs),followed by antigen processing and presentation by MHC class II molecules
  • 8.  DC activation and maturation through up- regulation of co stimulatory molecules and cytokine production, and stimulation of CD4+T helper cells, leading to the induction of strong humoral and cellular immune responses  Similar to native viruses, VLPs are processed in the cytosol of DCs and are presented by MHC class I molecules to cytotoxic CD8+T cells by the cross- presentation mechanism, inducing potent cytotoxic immune response
  • 9.  A number of VLP-based vaccine candidates, including GSK’s anti- malaria vaccine RTS,S, are in clinical development while many others, targeting pathogens such as influenza virus, rotavirus and human immunodeficiency virus are undergoing pre-clinical evaluation .
  • 11. To date, VLPs, non-enveloped and enveloped, have been produced for a number of targets using mammalian, plant , insect , yeast or bacterial cells and cell-free platforms
  • 12.  VLPs formed in yeast or insect larvae are purified after breaking the cells and incorporated with fish food pellets  Alternatively, purified VLPs are encapsulated and mixed into feed for oral delivery
  • 13.
  • 14. TYPES  Non-enveloped VLPs are typically composed of one or more components of a pathogen with the ability to self- assemble into particles and do not include any host components (Fig. 1A).  This approach has been used to develop vaccines against such pathogens as HPV and RV . Non-enveloped VLPs continue to be explored as a preferred approach for developing SUVs against a number of pathogens, including canine, mink and porcine parvoviruses using VP2 protein expressed in insect cells  In summary, non-enveloped VLPs can consist of a single or multiple components of a target pathogen or a single or multiple vaccine target antigens displayed on the VLP surface as afusion to a heterologous viral protein with the ability to self-assemble
  • 15.  Enveloped VLPs are relatively complex structures consisting of the host cell membrane (an envelope) with integrated target anti-gens displayed on the outer surface  Enveloped VLPs provide a higher degree of flexibility for integration of more antigens from the same or heterologous pathogens The most prominent examples of enveloped VLPs are VLPs engineered to express vaccine target antigens from influenza viruses retroviruses and hepatitis C virus (HCV)
  • 16.  Production of enveloped VLPs requires co-expression of several structural viral proteins, their assembly into particles, incorporation into host membranes and release of particles (budding) from the cell membrane For example, a successful assembly and bud-ding of influenza A/Udorn/72 (H3N2) VLPs have been achieved by co-expressing four structural proteins (hemagglutinin [HA], neuraminidase [NA], matrix protein M1 and ion channel protein M2) of the virus. In conclusion, enveloped VLPs represent complex structures consisting of multiple components of target pathogens and host membrane components and resemble the pathogen
  • 17. As Protein Delivery: Cell Culture Transfection Using Three Components: 1. Protein(Thereupetic Drug) 2. Structural Protein Isolated From Virus 3. Surface Proteins Dotted With Glycoproteins Used In Prostate Cancer