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Vaccines.

Vaccine : A natural or synthetic substance resembling or derived from a disease-causing agent and designed to incite immunity against this agent. Vaccination vs Immunization: While vaccination is the act of administering a vaccine, immunization indicates triggering protective immunity against the disease-causing agent..

Crude death rate for infectious diseases (USA). Anti-infection medicine highly contributed to global decrease in the frequency of death from infectious diseases.

Life expectancy globally and by world regions since 1770 10 — 1770 1800 Scuce Lite expectancy 1850 1900 1950 2015 — data 1990 WHO Bank data (by Max Rosen in Chta Ocean La Amoncas F ormer Sowet t.Jnon CC BY.SA.

Historical milestones. 1796, Edward Jenner used cowpox material to immunize humans against smallpox. 1885, Louis Pasteur, Rabies vaccine. Coined the term vaccine, from vacca (cow, latin ) honoring Jenner. 1900-1950s, typhoid, cholera, plague, influenza, and polio vaccines had been introduced..

Gives sustained protection Induces neutralizing antibody Induces protective T cens Practical considerations Vaccine must not itself cause illness or death Vaccine must protect against illness resulting from exposure to live pathogen Protection against illness must last for several years Some pathogens (such as polio virus) infect cells that cannot be replaced (e.g. neurons). Neutralizing antibody is essential to prevent infection of such cells Some pathogens, particularly intracellular, are more effectively dealt with by cell-rnediated responses LN' cost per dose Biological stability Ease of administration Few side-effects.

Active vs passive adaptive immunity. Natural Artificial Active Exposure to disease-causing agent Vaccination with disease-causing agent derivative (active vaccine/vaccination) Passive Transmission of antibodies via placenta/colostrum Administration of antibodies or sera against disease causing agent (passive vaccine/vaccination) Passive transfer of immune cells is referred to as “adoptive” immunization.

Attenuation Replication natural virus vaccine 8 Inactivated virus vROne The virulent parental virus Nonrecombinant. purified subunit Replication virus vector vaccine Bxterial cell Human APC RNA/DNA vaccines 00 Virus-like particle Protein Subunit.

Types of vaccines. Type of Vaccine Live attenuated or killed bacteria Live attenuated or"killed" viruses Subunit (antigen) vaccines Conjugate vaccines Synthetic vaccines Viral vectors DNA vaccines Examples Bacillus Calmette-Guérin, cholera Polio, influenza, rabies Tetanus toxoid, diphtheria toxoid Haemophilus influenzae, pneumococcus Hepatitis (recombinant proteins) Clinical trials of HIV antigens in canarypox vector Clinical trials ongoing for several infections.

Inactivated vs live-attenuated vaccine. Live-Attenuated Inactivated Definition Contains living microorganism altered not to cause disease. Contains microorganism treated with heat, chemicals or irradiation to kill the agent OR a toxin treated to inhibit its toxic effect (toxoid) OR may be a microorganism-derived factor/antigen. Toxoids and microorganism-derived factors/antigens are also referred to as subunit vaccines. Advantages Strong and longer-lasting immune response. Do not cause infection/disease Easier to manufacture and store/transport. Disadvantages May revert to pathogenic. Cannot be given to immunocompromised. More difficult to produce and store/transport (require refrigeration). Weaker immune response, typically require multiple shots..

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Virulence attenuation. Currently achievable in a more rapid and reliable manner using recombinant DNA techniques and genetic manipulation.

Inactivated vs live-attenuated vaccine. Inactivated virus Initial dose Third Time Replication competent virus vaccine nitial dose Amplification of injected dose Time.

What occurs when a booster dose of a vaccine is given?.

Conjugate vaccines. Some serious childhood-disease causing bacteria have an outer capsule composed of polysaccharides ex. Neisseria meningitidis , Streptococcus pneumoniae and Haemophilus influenzae. Defense against these highly relies on opsonization of the polysaccharide capsule with an antibody. The target of vaccination against these is therefore to elicit antibodies against their capsules..

Conjugate vaccines ( cntd ). Capsular polysaccharides are T-cell independent antigens. Children under the age of 2 years do not generate appropriate T-cell independent antibody responses and therefore cannot be vaccinated effectively with polysaccharide vaccines. An efficient way of overcoming this problem is to conjugate bacterial polysaccharides chemically to protein carriers that can be recognized by antigen-specific T cells. This converts a T-cell independent response into a T-cell dependent antibody response..

Conjugate vaccines. abstract. Ex. The Haemophilus influenzae type b (Hib) vaccine is a conjugate of bacterial polysaccharide + tetanus toxoid protein. B cell recognizes and binds the polysaccharide, internalizes and then degrades the entire conjugate Toxoid-derived peptides are subsequently presented on surface MHC class II molecules. T helper cells generated in response to earlier vaccination against toxoid recognize the complex on B-cell surface and activate the B-cell to produce anti-polysaccharide antibody. This antibody is protective against H. influenzae type b..

Untitled-1. Synthesis typically employs recombinant DNA technology. Propagation of viruses in a host is not necessarily the most efficient means of viral antigen production. Ex: Hepatitis B virus cannot be propagated in good quantities in host systems. Viral genes can be cloned and propagated in eukaryotic or prokaryotic cells for in vitro expression of viral antigens in mass quantities..

DNA/RNA vaccines. Rely on introducing a plasmid containing the DNA sequence/RNA encoding the antigen(s) into the appropriate tissues, production of target antigen(s) in the tissues thus eliciting an immune response against the antigen(s). None approved for human use until the SARS-CoV-2 other ex. clinical trials for HIV. Some were approved for veterinary use before that. Although they carry no risk of infection and are easy to produce and store, they raise concerns about host genome modulation, triggering immune responses against DNA itself and possible induction of tolerance to the antigen..

Vaccinate with tumor-antigen pulsed dendritic cell Dendritic cells pulsed with tumor antigens CD8+ T cell Tumor antigen presentation to patient's tumor- specific T cells Activation of tumor-specific T cells and killing of tumor cells.

a. Which of the following is theoretically the most effective vaccine against Bacterium X, a toxin-producing encapsulated bacterium?.

Vaccine adjuvants. An adjuvant is added to a vaccine to enhance immune responses. An adjuvant does not elicit an immune response against itself. Common adjuvants include a luminum salts, monophosphoryl lipid A, oil-in-water emulsions, synthetic CpG DNA sequences, etc. The majority of FDA approved vaccines contain Alum [ Aluminum hydroxide gel; Al(OH)3].

International Current Pharmaceutical Journal, 2015, 4:420-431.

Vaccine adjuvants. Mechanisms are not precisely defined, believed to include: Depot formation at the site of injection thought to result in slow release of antigen and longer exposure to immune system Convert soluble proteins into particulate matter hence enhancing uptake Local secretion of cytokines and chemokines at the site of injection resulting in recruitment of further immune cells Inflammasome activation.

Vaccine adjuvants. Mechanisms are not precisely defined, believed to include ( cntd ): Enhanced expression/activation of pattern recognition receptors (PRRs) May themselves mimic pathogen associated molecular pattern (PAMPs) Enhanced antigen presentation End result: mobilization of the innate arm of the immune system to elicit adaptive cellular and humoral immunity..

Herd immunity. A public health term that indicates a sufficient proportion of the population is immunized against a pathogen to reduce risk of passage of the disease to those not immunized..

Vaccination calendar in Lebanon. Lebanese National Vaccination Schedule.

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