Vaccination Flashcards
Vaccination discovery: Small pox
1796: Edward (Eddie) Jenner
- Used cowpox blisters from milk maid to incubate gardener’s son (wtf)
- protected boy from subsequent small pox infection (cow pox closely related to small pox)
Vaccines harness the Adaptive Immune system
Provide protective immunity through B memory cells:
Clonal selection –> Clonal Expansion –> Memory cells (and effectors)
Antibodies mediate humoral immunity
IgG important against blood-borne pathogens
IgA important against mucosal pathogens
Antibodies neutralise antigens:
- binding toxins to prevent them binding targets
- Preventing viruses from binding to host cell surface
- Preventing bacteria attaching to host cell
- Opsinising antigens for phagocytic uptake
- Activating Complement
CD4 T cells promoting antibody production
Important in humoral response to vaccines targeting non-protein antigens
Bind B cells via CD40 and cytokines
Activating Dendritic Cells in Vaccines
Vaccines MUST promote DC maturation to initiate an adaptive immune response. Activation done using Danger Signals:
- Direct Signals predominantly by TLRs
- Indirect signals by molecules who’s secretion is triggered by pathogens (TNFa or IL-1B)
Vaccines contain Adjuvants for DC activation
Vaccine Adjuvants
Component of vaccine containing ‘danger signals’; many vaccines have inherent adjuvant properties (e.g. Live attenuated vaccines)
- Alum-based
- MF59
- GSK Adjuvant System 04 (ASO4)
Alum-based adjuvants
Alum = precipitate of Aluminium Hydroxyphosphate
- Widely used (DTP, Hep A/B, Anthrax and Rabies)
- Activates inflammasome, promotes neutrophil infiltration and DAMP release
- Increases DC maturation/migration
- Promotes humoral immunity (poor activator of CTL immunity)
MF59 adjuvant
Oil-in-water adjuvant using squalene
- induces monocyte recruitment to injection site and DAMP release
- Increases DC migration and co-stimulatory molecule expression
- Used in humans: Flu vaccines
GSK Adjuvant System 04 (ASO4)
Combination of Alum with MonoPhosphoryl Lipid A (MPL)
- MPL = endotoxin-like molecule (less toxic than LPS) activating TLR4
- Increases co-stimulatory molecule expression
- Found in Cervarix (an HPV cervical cancer vaccine)
Vaccine Types
Live Attenuated
Inactivated
Subunit
Conjugate
Live Attenuated Vaccines
Diminished virulence with same antigens: attenuated by selection for reduced virulence in a cell culture (often has inherent adjuvant properties)
E.g. Sabin Oral Polio Vaccine
- Contains 3 attenuated strains of virus
- Orally administered: transiently infects host to stimulate IgA production (mucosal immunity)
- Risk of reverting to virulent form to cause Vaccine-Associated Paralytic Polio (shouldn’t be used in immunodeficient patients)
Inactivated Vaccines
Killed, unable to divide and no virulence risk
- Can be given to immunocompromised patients
- Unable to divide, don’t persist as long to create as strong an immunity
E.g. Salk Inactivated Polio Vaccine
- Contains 3 different strains of virus
- Grown in cell culture and inactivated with formaldehyde
- Administered by IM injection (less mucosal immunity than Sabin)
Subunit Vaccines
Contain parts of pathogen (associated proteins/inactivated toxins/non-protein antigens) that are a lot less immunogenic than whole pathogen (make up immunogenicity with multiple doses + adjuvants)
E.g. Gardisil (HPV vaccine)
- L1 capsid protein from HPV used but no nucleic acid so non-infectious
E.g. Tetanus toxoids vaccine
- The dangerous C.tetani toxin is inactivated with formaldehyde
- Requires Alum adjuvant to stimulate immunity
Conjugate vaccines
T cells can’t recognise polysaccharides so conjugation with proteins allows recognition of bacterial capsular polysaccharides
- enables antibody binding to polysaccharide
New Vaccine Approaches
1) Cancer vaccines containing DCs
- Loading DCs with tumour antigens/lysates can give a tumour-specific immune response
- DCs isolated from patients, pulsed with tumour antigen, reinserted
- Active Tumour-specific CD8 T cells
2) Heat Shock Proteins (HSPs) as adjuvants in cancer vaccination
- HSPs carry tumour’s peptide fingerprint (inc antigens)
- Purified from tumour and used to immunise same individual
