Biologics - Add? Flashcards
what are preventative vaccines?
Contain weakened or inactive antigens or pathogens, or genes for antigens that trigger an immune response within the body. This creates antibodies specific to these antigens, allowing a stronger secondary immune reaction when next infected by this pathogen.
What are therapeutic vaccines?
Administered after a disease or infection has already occurred. Often used to treat Cancer, Autoimmune disease (e.g. Coeliac disease and rheumatoid arthritis) or Chronic infections (e.g. HIV)
How are biologics delivered?
Viral vectors: viral vectors can stimulate direct tumouricidal effects and simultaneously elicit immune-enhancing responses from the payloads designed for the malignant target and its tumour microenvironment
Virus like particles
Nanomaterial delivery
Subcutaneous delivery:
Compounds with molecular weights <16kDa can reach systemic circulation via uptake by blood capillaries, higher molecular weights exhibit limited transport into blood capillaries and therefore enter circulation via lymphatic vessels
Whar are attenuated vaccines?
(modified live) -
Mostly viruses (MMR, flu, rotavirus, varicella) but also BCG and cholera (vaxchora). Active organisms that have lost virulence. Mild infections may occur
Not suitable for immunocompromised or pregnant people
Regulatory agencies now require molecular basis for attenuation (removal of genes)
Created by serial passage of the organism within cells
what are inactivated vaccines?
Whole agent vaccines, killed by heat or formaldehyde
Safer than attenuated but does not create strong memory response, can cause inflammatory response causing side effects. Require adjuvants, high dose or booster
E.g. Polio -
Contained virus from polio type 1,2 and 3. Inactivated by formaldehyde
Serial passage of virus in VERO cells in sub-physiological temperature allows mutations in virus
Can replicate in intestines but not nervous system. Can revert to wild type within host leading to disease
Used in countries with low risk of polio (pentavalent inactivated vaccine). Live attenuated is used in countries with high risk of polio outbreak
What are subunit vaccines?
Antigenic fragments, often conjugate vaccines. Antigenic polysaccharides from infecting agents used, usually serotype specific (should contain serotypes that cause disease)
More stable than other types (e.g., meningitis vaccine can withstand temperatures of up to 40°C)
Can be immunotolerant if polysaccharides are similar to human cell components
E.g. Toxoid vaccines -
Treats bacterial diseases – tetanus, C. difficile, Diptheria etc. Toxins from these bacteria are inactivated by formaldehyde to create toxoids
After activation the toxoid must keep the same structure of the toxin to be effective
E.g. pneumococcal vaccine – Streptococcus pneumoniae
Immunity required for each serotype as reinfection with another serotype can cause disease
2 different vaccines – for under 2 years old (pneumococcal conjugate vaccine) and for over 2 years (pneumococcal polysaccharide vaccine)
The polysaccharide vaccine is less robust immune response, no mucosal immunity provoke (no IgA) so respiratory tract infections are not prevented. Immunity lasts for 5-6 years, no response in under 2 years old and some adults
The conjugate vaccine is more robust, but a booster is still needed. Effective for young children and elderly. Less serotypes covered so infection from another serotype is likely. Mucosal immunity is triggered therefore carriage of these serotypes is reduced
What are recombinant vaccines?
Isolated DNA coding for antigen is taken from pathogen and inserted into DNA of a virus or cell. Virus or cell presents pathogen’s antigen
E.g. hepatitis B -
First recombinant vaccine, recombinantly produced in yeast cells, protein purified and prepared for storage
Requires 3 vaccinations for full protection and now thought to be protective for life
What are DNA vaccines?
Plasmids containing genes that encode an antigen are injected into host cells. Cells produce antigen from plasmid and body mounts a reaction to antigen
Still in experimental phase as immune response has not been significant
What are RNA vaccines?
Similar to DNA vaccine
mRNA of gene for antigen, transported with a vector into host cells, antigen displayed as foreign on MHC molecules
Synthetic production is possible. Can be designed within 1 week of identifying novel virus
HIV vaccine example
Uses Salmonella as a vector as both (HIV and salmonella) infect M cells in intestinal lining, salmonella is attenuated by removal of pathogenicity islands. contains a plasmid with antigen DNA with eukaryotic promoter
Still use the type III secretion system (one of the bacterial secretion systems to secrete effector proteins into host cell),
Ebola vaccine example
Live attenuated recombinant, replication competent vaccine
Vesicular stomatitis virus genetically engineered to express a glycoprotein from the Zaire Ebolavirus
Used so far in ring vaccination (strategy of vaccinating those most likely to be infected), not sure how long immunity lasts or if booster is needed
SARS-CoV-2 vaccine
Pfizer -
mRNA used to encode spike antigen, delivered in a lipid nanoparticle
95% effective but must be stored at -80°C
Astrazeneca -
Adenovirus vaccine with plasmid containing gene for spike protein
Non replicating virus (just delivers the DNA)
60-90% effective, more stable delivery system (normal cold temperatures required)
