Vaccine development Flashcards
What are vaccines?
a pharmaceutical preparation of an immunogenic substance or compound that induces an active immunity against a particular disease
can be prophylactic or therapeutic
What are the classifications of vaccines?
first generation
- live attenuated vaccines = BCG, shingles
- killed/inactivated vaccines
second generation
- subunit (peptide & protein) vaccines = tetanus toxoid
third generation
- DNA/mRNA vaccines
What is the MMR vaccine?
protects against three separate illnesses
- measles, mumps and rubella
What are the ingredients of the MMR vaccine?
pork gelatin - stabiliser
recombinant human serum albumin - stabiliser
may contain small amounts of eggs protein (vaccine is grown on cells from chick embryos)
small amounts of antibiotic, neomycin
- prevents bacterial growth during vaccine production and storage
What is the meningitis B vaccine?
protects against infection by meningococcal group B bacteria
Meningococcal infections can cause
- meningitis
- septicaemia (blood poisoning)
= which can lead to severe brain damage, amputations and even cause death.
What does an ideal vaccine consist of? How can they be prepared?
vaccine should consist of only the key antigenic determinants which will elicit a potent, specific immune response against the target pathogen
requires availability of either
- highly purified subunit antigens
- synthetic determinants
What are the advantages of synthetic vaccines?
they are devoid of unrelated antigenic determinants inherently present in vaccine extracts obtained from microbes
- do not induce undesirable side-effects seen in some conventional vaccines
What are the disadvantages of synthetic vaccines? How can this be countered?
they are weak immunogens primarily because of their relatively low molecular weight.
to counter this
- synthetic vaccines require the association of their synthetic antigenic moiety with an appropriate vaccine adjuvant.
What is the function of adjuvants in synthetic vaccines?
adjuvants improve the immunogenicity of weakly immunogenic compounds such as synthetic vaccines
- increases antigen specific responses
What are virosomes?
are made of viral envelopes with viral membrane components intercalated in the phospholipid bilayer membrane
are effective at cell targeting and fusion as the original virons
- deliver directly to the targeted cell
they have a improved safety profile over viruses
What is recombinant DNA technology?
it is a process for the production of a biological products such as proteins, hormones, enzymes using deoxyribonucleic acid (DNA).
What are the characteristics of plasmid DNA?
plasmids are extra chromosomal double stranded circular DNA
- are present in bacteria
they transport genetic information
What is the mechanism of DNA/mRNA vaccine therapy?
the carrier with DNA or mRNA encoding specific gene of interest binds to the host cell receptors
Transfection - DNA or mRNA loaded carrier enters the host cell for protein expression primarily via endocytosis
After the disruption of the endosomal membrane, DNA in the cytoplasm is
directed into the nucleus of the host cell (while mRNA proceeds for protein expression i.e. translation, without the need for transcription)
Transcription – the genetic information from DNA is transferred to mRNA in
the nucleus
Translation – mRNA is decoded to produce a specific protein (antigen in this case) in the cytoplasm with the help of ribosomes
The expressed protein (antigen) triggers an immune response in the host
How are DNA/mRNA vaccines typically deliver? What are the different types used?
most are delivered using a vector/vehicle
vectors
- colloidal vectors
= nanoparticles, microspheres, lipidic vesicles (liposomes), polymer condensed structures and micro emulsions
Why are colloidal carriers needed in DNA/mRNA vaccinations?
to protect the nucleic acid from premature inactivation in the presence of nucleases
to reduce side effects
to achieve relatively high nucleic acid concretion at the target site
to increase shelf life, easier sterilisation
to enhance the potential to engineer surface characteristics