Vaccine and passive immunity

primitive vaccine

attempt to induce infection

Edward jenner

founder modern vaccine (small pox), learn exposure to similar strain lead toimmunity because of similar antigens (milkmaid and cowpox)

Goals of vaccination

Eradicate disease, protect from infection, protect from symptoms/pathology

Vaccine properties (5)

Effective (stimulate correct IR), Duration, Safety, Stability, Cost

Vaccines and effectiveness

robust, need to stimulate correct IR (cell mediated or Ab mediated)

Vaccines and Duration

Short term - visit disease area (humoral), Long term (memory required), - naturally boosted by exposure (need booster if not exposed)

Vaccines and Safety

rigorous testing, avoid live attenuated bc can revert to WT, 1926 - live TB instead of BCG, 1942 - yellow fever contaminated with HBV

Vaccines and Stability

attenuated more stable at higher temp than inactive, maintaining cold chain(harder in resource poor countries)

Vaccines and Cost

resource poor regions, price of full course, transportaion/storage, society need (food?)

Types of vaccines

Live attenuated, inactive/killed, Conjugated, Toxoid, mRNA

Live/Attenuated whole agent vaccines

weaken microbs (minor mutation so doesn’t cause disease), mimics infection, stimulate antibody and cell mediated immunity, life long immunity (ex: MMRV), risk of revert back to wildtype, better for bacteria than virus bc bigger genome (where mutates)

Varicella (chicken pox)

DNA virus, latent in cell, cause shingle outbreak

Attenuated

microbs, artifically reduced virulence, majority of viral vaccines, encourage to grow at colder temps (25C)

Polio vaccine

Sabin oral vaccine (attenuated) revert back to virulent (1/1000000), lead to use of inactivated vaccine (NA and EU)

Attenuated bacterial vaccines

Calmetta and Guerin - BCG vaccine for TB, disadvantage - revert to virulent/disease in immunocompromised, current appraoch use genetically engineered mutants (avirulent)

BCG vaccine

protect severe disseminated TB and variable for pulmonary TB, attenuated bovine strain after 10yrs culture, Calmetta and Guerin

killed/ inactive whole agent vaccine

use when live vaccine not available or easily revert back, safer bc not infective, low immunogenicity (several doses needed), chemical inactivation in virus, Formaldehyde/phenol/acetone/heating inactivation for bacteria

Toxoids

Inactivated toxins - from purified proteins, immune response to toxoid, stimulates only antibody IR, require series of injections, short lived (B cell fade) - booster (DTaP)

type of subcellular fragments

Subunit vaccine, conjugated vaccines

Subunit vaccines

Subcellular fragment, only purified components, antigen stimulate antibody IR, extremely safe, Pneumoshot -capsule polysaccharide, Hep B (only DNA one) - viral coat protein

Conjugated vaccines

Subcellular fragments, for children immunity, polysaccharide antigen combined with protein antigen (stronger IR), Haemophilus influenzae - capsule w/ diphtheria toxoid

mRNA vaccines

don’t embed in nucleus, induce both IR (humoral/cell),nanolipids? travell through lymphoid to Dendritic cell, ssmRNA recognized by toll like receptors, more direct than andenovirus vaccines

Transfection vs transduction

Transfection - artifical way to transfer viral particle to host, Transduction - natural way (viral vector) to transfer viral particle to host

Viral Vector Vaccine

trigger both IR (humoral/cell), defective, into nucleus but can’t replicate, AdV like shuttle (capsule enters nucleus), dsDNA released into nucleus but not attached, booster don’t work for human strains bc cell recognize (can boost with non human strain)

Other vaccines type

Skin patches with Ag, Mucosal vaccines, Edible Plant vaccines

Skin patches with Ag

Ag taken up by langerhan’s cells (epidermis), carried to lymph nodes

Mucosal vaccines

Nasal drips fo URT infections

Edible Plant vaccines

expresse gene encoding bacterial/virus Ag in plant tissue, immunization through eating plant tissue

Adjuvant examples

CpG 1018 (Cytosine phosphoguanine), Matrix-M™ (saponin derived), AS01b (Monophosphoryl lipid A + QS-21)

Adjuvants

Increase immunity induced by vaccine, activate Toll like receptors (TLR) on dendritic cells, improve antigen presentation, Ag depot - persist and leak out slowly

Freund’s complete adjuvant

forbidden in humans (necrosis causing), for testing how vaccine work, dead mycobacteria and water in oil emulsion

Passive immunity

passive transfer of Ab - IgG, alternative for those already infected/ immunocompromised - try to control infection, pre-antibiotic era, large mammal (horse) used for production of antisera (Diphtheria/tetanus/pneumonia)

Challenges of Immunotherapy

Serum sickness - treat Ab as foreign and eliminate (because non human Ab), immune complex deposit in kidney and skin, hypersensitivity type 3, use Human sera to reduce complications

Passive immunotherapy uses

Rabies after exposure, Varicella - immunodeficient children, snakebites

Hypersensitivity

abnormal antigenic response, immune response to allergen

Hygiene hypothesis examples

Schistosoma infections have a strong protective effect against atopy (Increased atopy after anti-parasitic treatments), Necator americanus protect from asthma