Vaccines and immunization - PowerPoint Presentation

1. Vaccines and immunizationWhat is vaccination and how does it work?

2. Immunization saves lives and keeps people healthyImmunization saves up to 3 million lives annually Vaccines are available to protect against the following infectious diseases, with many more in development Cholera • Dengue • Diphtheria • Hepatitis A • Hepatitis B • Hepatitis E • Haemophilus influenzae type b (Hib) • Human papillomavirus • Influenza • Japanese encephalitis • Malaria • Measles • Meningococcal meningitis • Mumps • Pertussis (whooping cough) • Pneumococcal disease • Poliomyelitis • Rabies • Rotavirus • Rubella • Tetanus • Tick-borne encephalitis •Tuberculosis • Typhoid • Varicella (chickenpox) • Yellow Fever

3. How vaccines work? The body is exposed to a weakened or dead pathogenThe body’s immune cells make antibodies to attack the pathogen If the body is exposed to the pathogen again, the body will be prepared with antibodies

4. Protective Immunity Can Be Achieved by Active or Passive Immunization

5. Protective Immunity Can Be Achieved by Active or Passive ImmunizationActive Immunization The goal of active immunization is to trigger the adaptive immune response in a way that will elicit protective immunity and long-lived immunologic memory.

6. Passive immunization (No memory response, so protection is transient)Passive immunization :Transfer of antibodies from mother to fetus or the injection of antiserum against a pathogen or a toxin to provide immune protection. Without the development of memory B or T cells .

7. An immune response is induced by vaccines

8. We must first ask the following question before the development of a successful vaccine :What specific memory response do we need to have on hand before we encounter the real pathogen in order to be protected? The aim of the latter phases of clinical trials is to determine this empirically; have we in fact immunized individuals against this infectious agent?

9. In some cases circulating effector cells/molecules, in addition to memory cells, are required in order to establish protection, which depend on the incubation period of the pathogen:Influenza virus, which has a very short incubation period (1 or 2 days), disease symptoms are normally already underway by the time memory cells would be reactivated. Effective protection against disease from influenza therefore depends on maintaining high levels of neutralizing antibody via regular immunizations; those at highest risk are immunized each year, usually at the start of the flu season. For pathogens with a longer incubation period the presence of detectable neutralizing antibody at the time of infection is not always necessary. The poliovirus, for example, requires more than 3 days to begin to infect the central nervous system. An incubation period of this length gives the memory B cells time to respond by producing high levels of serum antibody. Thus, the vaccine for polio is designed to induce high levels of protective immunologic memory that can be recalled and reactivated once the virus is encountered.

10. There Are Several Vaccine Strategies, Each with Unique Advantages and Challenges

11. Live Attenuated Vaccines live attenuated vaccines produce the most robust response, although not without risk. Microorganisms are attenuated (disabled) so that they lose their ability to cause significant pathogenicity (disease) but retain their capacity for slow and transient growth within an inoculated host. This allows the immune system a taste of the real thing, but also the upper hand against a pathogen-like organism with only temporary residency. Attenuation can often be achieved in the laboratory by growing a pathogenic for prolonged periods under abnormal culture conditions. This selects mutants for example, an attenuated strain of Mycobacterium bovis, called bacillus Calmette-Guérin (BCG), was developed by growing M. bovis on a medium containing increasing concentrations of bile for 13 years had become sufficiently attenuated that it was suitable as a vaccine for tuberculosis.

12. Live Attenuated VaccinesGenetic engineering provides a means to attenuate a virus irreversibly, by selectively removing genes that are necessary for virulence or for growth in the host rendered the virus incapable of causing disease.One good example of a live attenuated vaccine that has been in use for decades worldwide is the oral polio vaccine (OPV) designed by Albert Sabin.The major disadvantage of attenuated vaccines is that these live forms can sometimes mutate and revert to a more virulent form in the host— a major drawback. In the case of polio, this can therefore risk paralytic disease in the vaccinated individual, or in unprotected individuals who come in contact with these more virulent forms shed in feces.Immunologically, this approach should provide better protection.

13. Inactivated or “Killed” Vaccines The killed pathogen, making it incapable of replication, but still allows it to induce an immune response to at least some of the immunogens (antigens) contained within the organism. It is critically important to maintain the structure of key epitopes on surface antigens during inactivation.Inactivation by heat or much better by chemicals (formaldehyde or various alkylating)killed vaccines often require repeated boosters to achieve a protective immune statusBecause they do not replicate in the host, killed vaccines typically induce a predominantly humoral/antibody responseA serious complication are some of the virus were not killed, leading to diseaseThe safety of inactivated vaccines is greater than that of live attenuated vaccines.Inactivated vaccines are commonly used against both viral and bacterial diseases, including the classic yearly flu vaccine and vaccines for hepatitis A, cholera and COVID-19. In addition to their relative safety, their advantages also include stability, and ease of storage and transport.

14. Inactivated vaccines

15. Subunit VaccinesMany of the risks associated with attenuated or killed whole-organism vaccines can be avoided with a strategy that uses only specific, purified macromolecules derived from the pathogen, known as a subunit approach. Three most common applications of this strategy are:Inactivated pathogen exotoxins (called toxoids) -- Diphtheria and tetanus Isolated capsular polysaccharides or surface glycoproteins -- Streptococcus pneumoniae (pneumonia) capsular polysaccharides (PCV13), and Neisseria meningitidisPurified key recombinant protein antigens -- The first recombinant antigen vaccine approved for human use is the hepatitis B vaccine.One limitation of some subunit vaccines, especially polysaccharide vaccines, is their inability to activate T cells. Instead, they typically activate B cells in a thymus-independent type 2 (TI-2) manner, resulting in IgM production but little class switching, no affinity maturation, and little, if any, development of memory cells.This can be avoided in vaccines that conjugate a polysaccharide antigen to a protein carrier, which induces T-cell responses against both the protein and polysaccharide.

16. Subunit vaccines

17. Recombinant Vector Vaccines live attenuated vaccines prolong immunogen delivery and encourage cell-mediated responses, but have the disadvantage that they can sometimes revert to pathogenic forms. Recombinant vectors maintain the advantages of the live attenuated vaccine approach while avoiding this major disadvantage of reversion. Individual genes that encode key antigens of especially virulent pathogens can be introduced into safe attenuated viruses or bacteria that are used as live carriers. The attenuated organism serves as a vector, replicating within the vaccinated host and expressing the individual gene product/s it carries from the pathogen.If the foreign gene product expressed by the vector, inducing development of both cell-mediated and antibody-mediated immunity.Eliciting immunity at the mucosal surface could provide excellent protection at the portal of entry for many common infectious agents, such as cholera and gonorrheaCOVID

18. Vector vaccines

19. DNA VaccinesDNA vaccines are based on plasmid DNA encoding antigenic proteins; the plasmid DNA is injected directly into the muscle of the recipient. This strategy relies on the host cells to take up the DNA and produce the immunogenic protein in vivo, thus directing the antigen through endogenous MHC class I presentation pathways, theoretically helping to activate better CTL responses. The delivered DNA plasmid to antigen-presenting cells (APCs) such as dendritic cells near the injection area is crucial to the development of antigenic responses to these vaccines.DNA vaccines are able to induce protective immunity against a number of pathogens, including influenza and rabies viruses.

20. DNA VaccinesDNA vaccines offer some potential advantages over many of the existing vaccine approaches:There is no denaturation or modification—the immune response is directed to the antigen in a three-dimensional structure similar to that seen in the pathogen, inducing both humoral and cell-mediated immunity. Strong stimulation of both arms of the adaptive immune response typically requires immunization with a live attenuated or recombinant vector preparation, which incurs additional risk. Induce prolonged expression of the antigen, enhancing the induction of immunological memory.No refrigeration of the plasmid DNA is required, eliminating long-term storage challenges.The same plasmid vector can be custom tailored to insert DNA encoding a variety of proteins, which allows the simultaneous manufacture of a variety of DNA vaccines for different pathogens, saving time and money.

21. mRNA vaccines

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23. There Are Several Vaccine Strategies, Each with Unique Advantages and Challenges Three key factors must be kept in mind in the development of a successful vaccine: the vaccine must be safeit must be effective in preventing infectionthe strategy should be reasonably achievable given the population in question. Population considerations can include:geographical locale, access to the target group (which may require several vaccinations)complicating co-infections or nutritional statesThe success of vaccine depend on the branch or branches of the immune system that are activated:Vaccine designers must target specific humoral and/or cell mediated pathways. Protection must also reach the relevant site of infection. development of long-term immunologic memory

24. In conclusion We described the most common vaccine strategies, some vaccines presently in use.Keep in mind: no one strategy, additive, or administration route is likely to work for all infectious agents, or even for all members of one type of pathogen, and many of these approaches can be applied in an à la carte fashion, depending on the situation.

25. Thank youADDITIONAL RESOURCES:Kuby immunology 8th edition, 2019Immunisationhttps://www.hse.ie/eng/health/immunisation/hcpinfo/guidelines/chapter3.pdf https://www.who.int/health-topics/vaccines-and-immunization#tab=tab_1