Narongdet Kositpantawong Fellow ID Prince of Songkla University

1. Adult Immunization Narongdet Kositpantawong Fellow ID Prince of Songkla University

2. Topic Basic immunization Immunizing agents Constituents Determinants of immunogenicity Temporal course of immune response Measurement of immune response Vaccine development Update recommendation of ACIP

3. Immunization Immunization is the act of artificially inducing immunity or providing protection from disease active or passive Active : vaccines or toxoids stimulate the body's immune system antibodies or cell-mediated immunity, or both, which protects against the infectious agent Passive : consists of providing temporary protection through the administration of exogenously produced antibody, 2 situation 1. Transplacental : protective first 3-6 monthsof life 2. Immunoglobulin injection : for specific purposes Mandell 7th edition 2010

4. Immunizing agents Vaccine a suspension of attenuated live or killed microorganisms (bacteria, viruses, or rickettsiae), or fractions administered to induce immunity and thereby prevent infectious disease Toxoid modified bacterial toxin rendered nontoxic retains the ability to stimulate the formation of antitoxin Mandell 7th edition 2010

7. Immunizing agents Immunoglobulin contains 15% to 18% protein obtained by cold ethanol fractionation of large pools of blood plasma. It is primarily indicated for 1. certain immunodeficient persons 2. passive immunization against measles and hepatitis A IVIg : special preparation for IV , indicate in Ig def. , Kawazaki and ITP Mandell 7th edition 2010

8. Immunizing agents Specific immunoglobulin special preparations obtained from donor pools preselected for high antibody content against a specific disease Example 1. hepatitis B immune globulin (HBIG) 2. varicella-zoster immune globulin (VZIG) 3. rabies immune globulin (RIG) 4. tetanus immune globulin (TIG) Mandell 7th edition 2010

9. Topic Basic immunization Immunizing agents Constituents Determinants of immunogenicity Temporal course of immune response Measurement of immune response Vaccine development Update recommendation of ACIP

10. Constituents of immunizing agents Suspending fluid This frequently is as simple as sterile water or saline it may be a complex fluid containing - small amounts of proteins or - other constituents derived from the medium or biologic system in which the immunizing agent is produced (serum proteins, egg antigens, cell culture–derived antigens) Mandell 7th edition 2010

11. Constituents of immunizing agents Preservatives, stabilizers, antibiotics - These components of vaccines are used for 1. to inhibit or prevent bacterial growth in viral culture or the final product 2. to stabilize the antigen - They include materials such as mercurials (thimerosal), gelatin, and specific antibiotics. - Allergic reactions may occur if the recipient is sensitive to any of these additives. - US : removed thimerosal for vaccine in children< 7yrs Mandell 7th edition 2010

12. Constituents of immunizing agents Adjuvants - An aluminum salt is used in some vaccines to enhance the immune response to vaccines containing inactivated microorganisms or their products (e.g., toxoids and hepatitis B vaccine). - usually be IM because SC or intracutaneous administration can cause local irritation, inflammation, granuloma formation, or necrosis - Oil-in-water adjuvants : enhanced immunogenicity for some vaccines such as inactivated influenza H5N1 vaccines Mandell 7th edition 2010

13. Immunologic Basis of Vaccination 2 major approach of active immunization the use of live (generally attenuated) infectious agents the use of inactivated, or detoxified, agents or their extracts For many diseases (including influenza, poliomyelitis, typhoid, and measles), both approaches have been employed Live attenuated vaccines are believed to induce an immunologic response more similar to that resulting from natural infection than do killed vaccines Mandell 7th edition 2010

14. Immunologic Basis of Vaccination Inactivated or killed vaccines can consist of inactivated whole organisms (e.g., Japanese encephalitis) detoxified exotoxin (e.g., diphtheria and tetanus toxoids) soluble capsular material either alone (e.g., pneumococcal polysaccharide) covalently linked to carrier proteins (e.g., Haemophilus influenzae type b conjugate vaccines) chemically purified components of the organism (e.g., acellular pertussis, inactivated influenza vaccines) recombinant proteins ( HPV , HBV ). Mandell 7th edition 2010

15. Topic Basic immunization Immunizing agents Constituents Determinants of immunogenicity Temporal course of immune response Measurement of immune response Vaccine development Update recommendation of ACIP

16. Determinants of immunogenicity chemical and physical states of the antigen genetic characteristics of the responding individual physiologic condition of the individual (e.g., age, nutrition, gender, pregnancy status, stress, infections, immune status) manner in which the antigen is presented (route of administration, dose or doses and timing of doses, and presence of adjuvants ) Mandell 7th edition 2010

17. LiveVS Killed or Subunit vaccine live vaccinesmultiply in the recipient, antigen production generally increases logarithmically until checked by the onset of the immune response it is intended to induce The live attenuated viruses (e.g., measles, mumps, and rubella) generally are believed to confer lifelong protection in those who respond. By contrast, killed vaccines generally do not induce permanent immunity with one dose making repeated vaccination and subsequent boosters necessary to develop and maintain high levels of antibody (e.g., diphtheria, tetanus, rabies, typhoid). Mandell 7th edition 2010

18. Exceptions to this general rule may include hepatitis B vaccine, for which long-term immunologic memory has been demonstrated for at least 10 years after vaccination inactivated polio vaccine (IPV), for which the duration of immunity is unknown Although the amount of antigen initially introduced is greater with inactivated vaccines, multiplication of organisms in the host results in a cumulatively greater antigenic input with live vaccines LiveVS Killed or Subunit vaccine Mandell 7th edition 2010

19. Most vaccines comprise protein antigens, which generate a T-cell–dependent immune response with induction of immunologic memory, booster effects on repeat administration, and good immunogenicity in all age groups However, purified bacterial capsular polysaccharide vaccines induce a T-cell–independent immune response, which does not lead to immune memory and cannot be boosted with repeated injections Polysaccharide vaccines have poor immunogenicity in infants and young children LiveVS Killed or Subunit vaccine Mandell 7th edition 2010

20. Covalent linkage of the polysaccharide to a carrier protein converts it from a T-cell–independent to a T-cell–dependent antigen (e.g. Hib, pneumococcal vaccine), which produces a good immune response in these important populations LiveVS Killed or Subunit vaccine Mandell 7th edition 2010

21. Dose The amount of antigen is important. insufficient amount may result in an absence of immune responsiveness usually a dose-response curve relationship between antigen dose and peak response obtained beyond a threshold however, responsiveness may reach a plateau, failing to increase beyond a certain level despite increasing doses of vaccine Mandell 7th edition 2010

22. Adjuvants The immune response to some inactivated vaccines or toxoids can be enhanced by the addition of adjuvants, such as aluminum salts. They are particularly useful with inactivated products, such as diphtheria and tetanus toxoids, and acellular pertussis vaccines (DTaP) and hepatitis B vaccine. The mechanism of enhancement of antigenicity by adjuvants is not well defined; however, it is increasingly clear that they activate the innate immune system through pathogen-associated molecular patterns (PAMPs). Mandell 7th edition 2010

23. Adjuvants Although aluminum salts are currently the only licensed adjuvants for use in humans in the United States other adjuvants based on oil-in-water emulsion of squalene or monophosphoryl lipid A have shown promising results Mandell 7th edition 2010

24. Route of administration The route of administration can determine the nature of the immune response to a vaccine or toxoid. IM and SC delivery results in a predominantly IgG response. Oral or nasal vaccination is more likely to result in production of local IgA compared IM injection, although systemic IgG also is induced However, there is increasing interest in the intradermal route, particularly with the potential of reducing the amount of antigen per dose, thereby decreasing strains on production capacity and potentially vaccine cost Mandell 7th edition 2010

25. Age The immune response to vaccine varies with age Children and young adults usually respond well to all vaccines Differences in response capability exist during early infancy and old age First few months of life has passively acquired maternal antibody impaired initial immune response to some killed vaccine ( eg. hepattis A , diphtheroid toxin) and many lived vaccine (eg.measle ) In elderly people , the response to antigenic stimulation may be deminished (eg. Influenza , HBV vaccine ) Mandell 7th edition 2010

26. Topic Basic immunization Immunizing agents Constituents Determinants of immunogenicity Temporal course of immune response Measurement of immune response Vaccine development Update recommendation of ACIP

27. Temporal course of IR

28. Topic Basic immunization Immunizing agents Constituents Determinants of immunogenicity Temporal course of immune response Measurement of immune response Vaccine development Update recommendation of ACIP

29. Measurement of IR Waning immunity loss of long lived memory B or T cells , in the absence of repeated exposure of pathogen Evaluating persistent of Ab : determine duration of vaccine induced immunity However , absence of measurable of Ab may not mean that the individual is unprotected A fall in titer takes place for some vaccines over time (eg. Measle , rubella , hepatitis B) , on revaccination or challenge , a rapid secondary response is observed on IgG Ab with little or no detectable IgM , suggesting persistent protection Mandell 7th edition 2010

30. Measurement of IR Fuctional Ab is important in assessing immunity to bacterial polysaccharide vaccine Opsonophagocytic activity (OPA) : assay of choice of monitor vaccine response , because vaccine also induce nonfunctional Ab that are detected in EIA (enzyme immunosorbant assay) The measurement of CMIR is usually limited Mandell 7th edition 2010

31. Topic Basic immunization Immunizing agents Constituents Determinants of immunogenicity Temporal course of immune response Measurement of immune response Vaccine development Update recommendation of ACIP

32. Vaccine development Conventional techniques : most vaccines in use today Live attenuated viral vaccines organisms are repeatedly passaged in various tissue culture cell lines to reduce virulent properties while maintaining immunogenicity. Inactivated vaccines growing microorganisms  concentration, purification and inactivation Component vaccines usually are derived from chemical separation of the needed component from the parent organism Mandell 7th edition 2010

33. Vaccine development Future vaccines : new methods of biotechnology—especially recombinant techniques. Currently available hepatitis B vaccines were developed by cloning the HBsAg gene into yeast, leading to synthesis of HBsAg within the yeast cell Live vectors one or more genes encoding critical determinants of immunity from pathogenic microorganisms  genome of the vector These vectors may include viruses such as poxviruses (vaccinia or canarypox) or bacteria such as salmonella or bacillus Calmette-Guerin : BCG) Mandell 7th edition 2010

34. Vaccine development Microencapsulation critical Ag in polymers that can lead to sustained release or pulse release over prolonged periods mimicking the effect of multiple injections of an antigen over a several-month interval. Nucleic acids encode critical antigens injection of the DNA leads to production of antigen without risk for producing whole infectious organisms. Example : live attenuated influenza vaccine ( genetic reassortment of the genes ) Mandell 7th edition 2010

35. Vaccine development

36. Recommendation of Adult immunization

37. Change in chart (20102011) Incorporated universal influenza vaccination Re-ordered list of vaccines to keep all universally-recommended vaccines together (i.e., influenza, Td/Tdap, VAR, HPV, ZOS)

40. Influenza vaccine

41. Highlights:2010 recommendations annual vaccination be administered to all persons aged ≥6 months for the 2010–11 influenza season children aged 6 months–8 years vaccination status is unknown never received seasonal influenza vaccine before or who received seasonal vaccine for the first time in 2009–10 but received only 1 dose in their first year of vaccination who did not receive at least 1 dose of an influenza A (H1N1) 2009 monovalent vaccine regardless of previous influenza vaccine history should receive 2 doses of a 2010–11 seasonal influenza vaccine (minimum interval: 4 weeks) during the 2010–11 season; MMWR 2010;59:989-92.

42. Highlights:2010 recommendations vaccines containing the 2010–11 trivalent vaccine A/California/7/2009 (H1N1)-like (the same strain as was used for 2009 H1N1 monovalent vaccines), A/Perth/16/2009 (H3N2)-like B/Brisbane/60/2008 information about Fluzone High-Dose, a newly approved vaccine for persons aged ≥65 years information about other standard-dose newly approved influenza vaccines and previously approved vaccines with expanded age indications MMWR 2010;59:989-92.

43. MMWR 2010;59:989-92..

44. N Engl J Med 2009;361:1935-44.

45. 272 hospitalized patients, 19 patients (7%) died; The median age of patients who died was 26 years (range,1.3 to 57); 13 patients who died (68%) had an underlying medical condition N Engl J Med 2009;361:1935-44.

46. JAMA2009;302:1872-9.

47. JAMA2009;302:1872-9.

48. Lancet. 2009 ;374:2072-9

49. “ However, randomized controlled trials cannot be performed ethically in populations for which vaccination already is recommended, and in this context, observational studies that assess outcomes associated with laboratory-confirmed influenza infection also can provide important vaccine or antiviral safety and effectiveness data ” MMWR 2010;59:989-92.

50. Summary of influenza vaccination recommendations, 2010 All persons aged ≥ 6 months should be vaccinated annually When vaccine supply is limited, vaccination efforts should focus on delivering vaccination to persons who aged 6 months– 4 years aged ≥ 60 years are immunosuppressed chronic pulmonary (including asthma), cardiovascular (except HT), renal, hepatic, neurologic, hematologic, or metabolic disorders (including DM) pregnant aged 6 months–18years and receiving long-term aspirin therapy residents of nursing homes and other chronic-care facilities morbidly obese (BMI ≥40) health-care personnel household contacts and caregivers of children aged <5 years and adults aged ≥50 years household contacts and caregivers of persons with medical conditions that put them at higher risk for severe complications from influenza. MMWR 2010;59:989-92.