Immunoglobulins mmunoglobulinsand immunoglobulins

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1. IMMUNOPROPHYLAXIS 1 COMPETENCY NO. MI 1.9 TEACHING LEARNING METHOD: LECTURE DATE: 29.10.2024 DR. BLESSINA PAULIN. T III YR M.D MICROBIOLOGY

2. LEARNING OBJECTIVES 2 Active immunoprophylaxis Types of vaccines Cold chain and Vaccine vial monitor National Immunization Schedule 2020 Passive immunoprophylaxis

3. IMMUNOPROPHYLAXIS 3

4. IMMUNOPROPHYLAXIS 4 Immunoprophylaxis against microbial pathogens can be classified into: Active immunoprophylaxis (or vaccination) Passive immunoprophylaxis (or immunoglobulin administration)

5. VACCINATION (ACTIVE IMMUNOPROPHYLAXIS) 5

6. VACCINATION (ACTIVE IMMUNOPROPHYLAXIS) 6 Vaccine: Immunobiological preparation - provides specific protection against a given disease.

7. VACCINATION - HISTORY 7 History : Terms vaccine and vaccination - derived from ‘ Variolae vaccinae ’ (smallpox of the cow), the term devised by Edward Jenner to denote cowpox. Later, Louis Pasteur proposed that these terms should be extended to cover all the new protective preparations being developed, in memory of Edward Jenner.

8. VACCINATION - VALENCY 8

9. VACCINATION HOMOLOGOUS & HETEROLOGOUS 9

10. VACCINATION HOMOLOGOUS & HETEROLOGOUS 10 Heterologous - Examples Jenner's use of cowpox to protect against smallpox. Use of BCG vaccine made from Mycobacterium bovis to protect against human tuberculosis caused by M.tuberculosis .

11. VACCINE - TYPES 11

12. LIVE ATTENUATED VACCINE 12 Prepared from live (usually attenuated) organisms . Attenuated (by passing the live organisms serially through a foreign host) live organisms lose the ability to induce full blown disease ; but retain their immunogenicity.

13. LIVE ATTENUATED VACCINE – CONTD. 13 Bacterial Viral Live attenuated vaccines BCG vaccine Measles vaccine Typhoral vaccine Mumps vaccine Epidemic typhus vaccine Rubella vaccine   Live attenuated influenza vaccine   Chicken pox vaccine   Oral polio vaccine(OPV, Sabin vaccine)   Rotavirus vaccine   Yellow fever 17D vaccine   Hepatitis A   Japanese B encephalitis(14-14-2 strain)

14. LIVE ATTENUATED VACCINE – CONTD. 14 Small pox vaccine is the only live vaccine which is not attenuated . The non-pathogenic cross reactive Vaccinia virus or cowpox virus were used to vaccinate against small pox virus (i.e. Variola ).

15. LIVE ATTENUATED VACCINE – ADVANTAGES 15 More potent immunizing agent compared to killed vaccines Live organisms multiply in the host and the resultant antigenic dose would be larger than what is administered. Retain all the immunogenic components (major and minor) of the organisms. Capable of inducing mucosal immunity by stimulating secretory IgA antibody production at the local mucosal sites.

16. PRECAUTIONS WHILE USING LIVE ATTENUATED VACCINES 16 Contraindications In immunodeficiency diseases In any conditions that supresses the immunity such as leukaemia, lymphoma, malignancies Corticosteroid or any other immunosuppressive drug therapy Pregnancy

17. PRECAUTIONS WHILE USING LIVE ATTENUATED VACCINES 17 Dosage - Single dose. Exception – OPV When two live vaccines are required to be given – administered at 4 weeks interval . Exception – Yellow fever vaccine (<4 wks after MMR)

18. PRECAUTIONS WHILE USING LIVE ATTENUATED VACCINES 18 Risk of gaining the virulence - The attenuation of the live vaccine has to be done in an effective way otherwise there is always a risk of gaining the virulence back again. Storage - Stored cautiously to retain effectiveness (Esp. OPV and measles).

19. INACTIVATED OR KILLED VACCINE 19 Consists of organisms, which are grown in culture under controlled conditions and then killed using methods such as heat or formaldehyde. Safer but less efficacious than live vaccines. Killed vaccines require large doses, adjuvants, and multiple doses to confer immunity. In most cases, a booster dose is also needed.

20. INACTIVATED OR KILLED VACCINE – CONTD. 20 Adjuvants increase the immunogenicity of the vaccine antigen (e.g. alum is used as adjuvant in DPT vaccine) Killed vaccines – administered in - subcutaneous or intramuscular routes . Absolute contraindication - severe local or general reaction to the previous dose.

21. INACTIVATED OR KILLED VACCINE – CONTD. 21 Killed/Inactivated vaccine Bacterial Viral Typhoid vaccine Injectable polio vaccine (IPV or Salk vaccine) Cholera vaccine Killed influenza vaccine Pertussis vaccine Rabies vaccine Plague vaccine Hepatitis A   Japanese B encephalitis vaccine

22. CHARACTERISTICS OF KILLED AND LIVE VACCINES 22 Characteristic Killed Vaccine Live Vaccine Number of doses Multiple Single Need for adjuvant Yes No Duration of immunity Shorter Longer Effectiveness of protection Lower Greater Mimics natural infection Less closely More closely Immunoglobulins produced IgG IgA and IgG Mucosal immunity Absent Induced

23. CHARACTERISTICS OF KILLED AND LIVE VACCINES 23 Characteristic Killed Vaccine Live Vaccine Cell-mediated immunity Poor Induced Reverse back to virulent form No Possible Excretion of vaccine virus and transmission to non-immune contacts No Possible Interference by other microorganisms in host No Possible Stability at room temperature High Low Immunodeficiency and pregnancy Safe Unsafe

24. TOXOID VACCINE 24 Exotoxins produced by certain bacteria can be detoxicated to form toxoid How?? by treating with acidic pH, formalin or by prolonged storage. Toxoid is a form of toxin that loses its virulence property but retains immunogenicity.

25. TOXOID VACCINE – CONTD. 25 Induces formation of neutralizing antibodies that are capable of neutralizing the toxin moiety produced during an infection; rather than acting upon the organism. Toxoid vaccine DT (Diphtheria toxoid)   TT (Tetanus toxoid)  

26. EXTRACTED OR CELLULAR FRACTIONS VACCINE 26 Prepared from extracted cellular fractions. Cellular fraction (Capsular polysaccharide Ag) Meningococcal vaccine   Pneumococcal vaccine   Haemophilus influenzae type (Hib) vaccine

27. SUBUNIT VACCINES 27 For certain viruses, only a particular subunit of the virus is necessary to initiate the infection.e.g . hepatitis B surface antigen ( HBsAg ) is the immunogenic component of hepatitis B virus. So, the subviral component alone can be used as vaccine rather than the whole virus.

28. SUBUNIT VACCINES – CONTD. 28 DNA recombinant technology is used for the preparation of such sub viral components Subunit vaccine Hepatitis B   HPV(Human papilloma virus) vaccine  

29. COMBINATIONS 29 If more than one immunizing agents are included in a vaccine preparation, it is called as combined vaccine. Aim of the combined vaccine is to: Simplify administration and Augment the immunogenicity of the immunogen.

30. COMBINATIONS – CONTD. 30 Combined vaccine Bacterial Viral DPT vaccine (Diphtheria, pertussis and tetanus) MMR vaccine (mumps, measles, rubella)   Penta valent vaccine (DPT + Hib + Hepatitis B)

31. NEWER VACCINE APPROACHES - DNA VACCINE 31 Experimental at present. Advantages: Cost effective Mounting a stronger and wider range of immune response.

32. DNA VACCINE – CONTD. 32 Small pieces of DNA containing genes from the pathogenic microorganism are injected into the host. The gene of interest gets integrated with the host cell genome and starts transcribing the proteins against which the host mounts an immune response. Several vaccine trials are going on based on DNA vaccines.

33. NEWER VACCINE APPROACHES - EDIBLE VACCINE 33 New concept introduced recently. Gene encoding the orally active antigenic protein is isolated from the pathogen and is transferred to suitable plant bacteria, which are then used to infect a transgenic plant (e.g. banana, potato etc.).

34. EDIBLE VACCINE – CONTD. 34 Plants infected by the bacteria then start producing the antigen of interest in large scale. Appropriate plant parts having the antigen may be fed raw to animals or humans to bring about immunization.

35. EDIBLE VACCINE – CONTD. 35 Advantages: Low cost Ability to produce in large scale Administered orally Induces local immunity Heat stable

36. EDIBLE VACCINE – CONTD. 36 Applications - The edible vaccines are still under experimental stage; some formulations available include - Transgenic potatoes and tomatoes against diarrheagenic organisms Edible banana against Norwalk virus

37. COLD CHAIN 37 System of transport, storage, and handling of vaccines , starting at the manufacturer level and ending with the site of administration of the vaccine to the client. Optimum temperature: Refrigerated vaccines: between +2°C and +8°C . Frozen vaccines: -15°C or lower.

38. COLD CHAIN – CONTD. 38 Protection from light is a necessary condition for some vaccines. Improper cold chain maintenance is one of the most common causes of vaccine failure ; especially oral polio vaccine which is the most sensitive vaccine to heat; must be stored at - 20 C.

39. COLD CHAIN – CONTD. 39 Storage: Freezer compartment - polio and measles COLD part but never allowed to freeze - DPT, TT, td, BCG, hepatitis B, H.influenzae type b and diluents.

40. VACCINE VIAL MONITOR 40 Tool to monitor the stability/potency of a vaccine and to check the efficiency of cold chain. It is heat sensitive label lining the vaccine vial. Contains an outer blue circle and an inner white square.

41. VACCINE VIAL MONITOR – CONTD. 41 With increase of time and temperature , the inner square changes its color gradually from white towards blue , whereas the outer circle is not heat sensitive; it remains blue throughout.   Inner square Outer circle Vaccine Stage-1 White Blue Can be used Stage-2 Light blue Blue Can be used Stage-3 Blue Blue Discard Stage-4 Dark blue Blue Discard

42. NATIONAL IMMUNIZATION SCHEDULE 2020 (NIS) FOR INFANTS, CHILDREN AND PREGNANT WOMEN 42 Vaccine When to give Maximum age Dose Dilution Route Site For pregnant women TT/Td-1 Early in pregnancy   0.5 mL No IM Upper arm TT/Td-2 4 weeks after TT/Td-1 <36 weeks of pregnancy (if missed,   can   be   given later)   0.5 mL No IM Upper arm TT/Td- Booster If received 2 TT/Td doses in a pregnancy within the last 3 years 0.5 mL No IM Upper arm

43. NATIONAL IMMUNIZATION SCHEDULE 2020 (NIS) FOR INFANTS, CHILDREN AND PREGNANT WOMEN – CONTD. 43 Vaccine When to give Maximum age Dose Dilution Route Site For infants BCG At birth or as early as possible Till 1 year 0.05 mL (0.1 mL for >1 month) Saline ID Left upper arm Hepatitis B - Birth dose At birth or as early as possible Within 24 hour 0.5 mL No IM Anterolateral side of mid-thigh OPV-0 At birth or as early as possible Within first 15 days 2 drops No Oral Oral

44. NATIONAL IMMUNIZATION SCHEDULE 2020 (NIS) FOR INFANTS, CHILDREN AND PREGNANT WOMEN – CONTD. 44 Vaccine When to give Maximum age Dose Dilution Route Site For infants OPV 1, 2 and 3 At 6 weeks, 10 weeks and 14 weeks 5 years of age 2 drops No Oral Oral Pentavalent 1, 2 and 3 At 6 weeks, 10 weeks and 14 weeks 1 year of age 0.5 mL No IM Anterolateral side of mid-thigh PCV (3 doses) At 6 weeks and 14 weeks, booster at 9-12 months - 0.5 mL   IM Anterolateral side of mid-thigh

45. NATIONAL IMMUNIZATION SCHEDULE 2020 (NIS) FOR INFANTS, CHILDREN AND PREGNANT WOMEN – CONTD. 45 Vaccine When to give Maximum age Dose Dilution Route Site For infants Rotavirus At 6 weeks, 10 weeks and 14 weeks 1 year of age 5 drops No Oral Oral IPV Two fractional doses at 6 and 14 weeks of age 1 year of age 0.1 mL No ID Right upper arm Measles /MR 1 st dose 9 completed months–12 months 5 years of age (only measles vaccine) 0.5 mL Sterile water SC Right upper arm

46. NATIONAL IMMUNIZATION SCHEDULE 2020 (NIS) FOR INFANTS, CHILDREN AND PREGNANT WOMEN – CONTD. 46 Vaccine When to give Maximum age Dose Dilution Route Site For infants JE - 1 9 completed months–12 months 15 years of age 0.5 mL Phosphate buffer SC Left upper arm Vitamin A (1st dose) At 9 completed months, given along MR vaccine 5 years of age 1 mL (1 lakh IU) No Oral Oral

47. NATIONAL IMMUNIZATION SCHEDULE 2020 (NIS) FOR INFANTS, CHILDREN AND PREGNANT WOMEN – CONTD. 47 Vaccine When to give Maximum age Dose Dilution Route Site For Children DPT booster-1 16–24 months 7 years of age 0.5 mL No IM Anterolateral side of mid-thigh MR 2nd dose 16–24 months 5 years of age 0.5 mL Sterile water SC Right upper arm OPV Booster 16–24 months 5 years of age 2 drops No Oral Oral JE-2 16–24 months   0.5 mL Phosphate buffer SC Left upper arm

48. NATIONAL IMMUNIZATION SCHEDULE 2020 (NIS) FOR INFANTS, CHILDREN AND PREGNANT WOMEN – CONTD. 48 Vaccine When to give Maximum age Dose Dilution Route Site For Children Vitamin A (2nd to 9th dose) 16–18 months. Then one dose every 6 months up to the age of 5 years 5 years of age 2 mL (2 lakh IU) No Oral Oral DPT Booster-2 5–6 years 7 years of age 0.5 mL No IM Upper arm TT/Td 10 years and 16 years 0.5 mL No IM Upper arm

49. PASSIVE IMMUNOPROPHYLAXIS (IMMUNOGLOBULINS) 49

50. PASSIVE IMMUNOPROPHYLAXIS (IMMUNOGLOBULINS) 50 Given in the form of readymade immunoglobulins prepared against the pathogenic microorganism. Unlike vaccines, immunoglobulins act faster , without involvement of host immune apparatus .

51. PASSIVE IMMUNOPROPHYLAXIS (IMMUNOGLOBULINS) – CONTD. 51 Useful in the following circumstances: For immunocompromised individuals who cannot synthesize antibodies. For post exposure prophylaxis - to achieve an immediate effect. For the treatment of toxin mediated diseases - to ameliorate the effect of toxin (Antibiotics cannot neutralize the toxin - cannot be used for the treatment of toxin mediated diseases)

52. PASSIVE IMMUNOPROPHYLAXIS (IMMUNOGLOBULINS) – CONTD. 52 Immunoglobulin preparations Source Indications Diphtheria antitoxin Equine Treatment of respiratory diphtheria Tetanus immune globulin  (TIG) Equine, Human Treatment of tetanus as PEP, for people not adequately immunized with tetanus toxoid Botulinum antitoxin Equine, Human Treatment of botulism Varicella-zoster immune globulin (VZIG) Human PEP for immunosuppressed contacts of acute cases or new born contacts Cytomegalovirus immune globulin (CMV-IG) Human PEP in hematopoietic stem cell and kidney transplant recipients Rabies immune globulin (RIG) Equine, Human Treatment of rabies & PEP in people not previously immunized with rabies vaccine

53. PASSIVE IMMUNOPROPHYLAXIS (IMMUNOGLOBULINS) – CONTD. 53 Immunoglobulin preparations Source Indications Hepatitis B immune globulin (HBIG) Human PEP for- Percutaneous or mucosal or sexual exposure Newborn of mother with HBsAg + ve Hepatitis A immune globulin (HAIG) Human Post exposure prophylaxis for Family contacts Travelers Rubella Human Women exposed during early pregnancy Measles Human Infants or immunosuppressed contacts of acute cases exposed < 6 days previously Rh- isoimmunization ( RhIG ) Human Treatment – Rh- ve mother on delivery of a Rh+ve baby

54. VACCINE - TYPES 54

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56. THANK YOU 56