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Vaccines and antisera
This document summarizes key information about vaccines and immunity: 1. It describes active and passive immunity and how vaccines work to stimulate active immunity through antibody production. 2. It explains herd immunity and how widespread vaccination benefits unvaccinated individuals by making disease transmission unlikely. 3. It provides an overview of different types of vaccines including live attenuated, killed/inactivated, toxoid/subunit, and recombinant vaccines. 4. Examples are given of specific vaccines for diseases like tuberculosis, typhoid, cholera, pertussis, polio, rabies, hepatitis B, and measles/mumps/rubella.
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Vaccines and antisera
- 1. Vaccines and Antisera DrNaser Ashraf Tadvi
- 2. Immunity • Active Immunity •Development of antibodies by individual himself • It can be natural & species specific (horse, dogs, rats -TB) • It can be produced by introduction of an antigen • Passive immunity • Acquired by transfer of antibodies from donor to recipient • Natural: fetus receiving maternal antibodies • Acquired: by administration of sera containing immunoglobulins
- 3. Herd Immunity • Vaccinationof a portion of population (Herd) provides protection to unprotected individuals • Difficult to maintain a chain of infection when large population immune • If herd immunity is sufficiently high, occurrence of epidemic highly unlikely • May lead ( not necessarily) to elimination of disease in due course • Achieved in diseases like diphtheria and poliomyelitis • Neither possible nor necessary to achieve 100% herd immunity in a population to halt epidemic or control disease ( no definite answer) • Herd immunity may be determined by serological surveys
- 4. Vaccine • Immuno-biological substancedesigned to produce specific protection against a given disease • Stimulates production of protective antibody and other immune mechanisms • May be prepared from • Live modified organisms • Inactivated or killed organisms • Extracted cellular fractions , toxoids (Subunit vaccines)
- 5. Types of vaccines Live attenuated Killedwhole organism Toxoid/ Protein Polysaccharide Glycoconjugate Recombinant • BCG • Ty 21a (Oral) • OPV • Mumps • Measles • Rubella • Varicella • Yellow fever • Typhoid- Paratyphoid(TAB) • Cholera • Pertussis • Plague • Polio (IPV) • Rabies (PCEV, HDCV, PVRV) • HAV • Diptheria • Tetanus • Vi Typhoid Polysaccharide • Hib • Pneumococcus • HBV • HPV
- 6. Live attenuated vaccines •Prepared from live or wild (attenuated) organisms • These organisms have been passed repeatedly in laboratory in tissue culture or chick embryos and lost their ability to produce full blown disease but retain their immunogenicity • More potent than killed vaccines
- 7. Contraindications of livevaccines • Leukemia or other malignancies, especially receiving cytotoxic drugs • Pregnancy • SLE • Corticosteroid recipients • AIDS and other immune deficiency states • If two lives vaccines need to be given • Give simultaneously at different sites or with gap of atleast 3 weeks
- 8. Killed (Inactivated) Vaccines •Growing virus or bacteria in culture media then inactivating them with heat/ chemicals (usually formalin) • Usually safe but less efficacious • Usually administered by SC/IM route • Usually shortlasting immunity, booster doses are needed at intervals Typhoid-Paratyphoid(TAB) Cholera Pertussis Plague Polio (IPV) Rabies (PCEV, HDCV, PVRV) HAV
- 9. Toxoids • Modified bacterialexotoxins • Toxicity is lost but antigenicity is retained • Highly efficacious and safe immunizing agents
- 10. Other components invaccine (Excipients) • Adjuvants • Substances added to enhance degree or duration of immune response • Aluminium salts • Antibiotics • Added to prevent bacterial contamination of tissue culture cells • MMR vaccine , IPV vaccine (Neomycin) • Preservatives • Thiomersal, formaldehyde • Stabilizers • Lactose, sodium and potassium salts, human serum albumin, gelatin
- 11. Typhoid vaccine Parenteral • Typhoid-Paratyphoid A,B (TAB) • S. Typhi 109, S. paratyphi 7.5 x 108/ ml • Dose: 0.5 ml s.c , 2-3 injections at 2-4 weeks interval • Vi typhoid polysaccharide vaccine • Purified Vi capsular antigen of S.typhi • More effective and longer lasting • Dose: 0.5 ml s.c/i.m • Repeat after 3 years Oral • Typhoid-Ty21a Oral vaccine • Prepared from Ty21a attenuated strain of S.Typhi • Lodges in intestinal mucosa & prevents S.Typhi invasion of gut • Also imparts systemic immunity • Efficacy better than TAB • 67-90% protection for 3 years • 1 capsule alternate days in between meals (3 doses)
- 12. Cholera vaccine • Suspensionof phenol/ formalin killed inaba and ogawa strains of V. cholerae • 8x 109 organisms/ ml • Dose: 0.5 ml s.c/i.m followed by 1 ml 1-4 weeks later • Immunity produced in <50% and lasts only 6 months
- 13. Pertussis vaccine • 2x108/ml suspension of killed B. Pertussis • 0.5 ml i.m, 3 doses at 4-week interval • Adverse effects: • Local pain, induration, high fever • Hypotonic hyporesponsive child • Convulsions, focal neurological symptoms • Contraindications • History of convulsions or other neurological signs
- 14. Meningococcal vaccine • PurifiedPolysaccharide capsular antigen of N.meningitis • Used in epidemics • 0.5 ml single dose in > 2-year age • Adverse effects: • Transient fever, local reaction
- 15. H.Influenza type b(Hib) • H. influenza is important cause of meningitis and pneumonia among children in developing countries • High cost • Often given with DPT and polio vaccine • Generally not given to children > 24 months old
- 16. BCG vaccine • Liveattenuated vaccine against Tuberculosis • Induces Cell mediated immunity • Available as lyophilised (freeze dried) powder • Reconstituted with sterile normal saline • Dose – 0.05ml (neonates) , 0.1ml (infants and children) • Route of administration – intradermal
- 17. Poliomyelitis vaccine • Oralpoliovirus vaccine ( Sabin) • Inactivated poliomyelitis vaccine (Salk)
- 18. Oral Polio vaccine •Poliovirus family of Picornaviridae • The virus (type I, 2, 3) is grown in monkey kidney cell culture • The virus invades the nervous system & can cause permanent paralysis • Types of oral polio vaccine (Sabin) • Trivalent, bivalent, monovalent • Dose: 2 drops directly in mouth • Given at birth then 6, 10, 14 weeks, booster between 15-18 months and at school entry
- 19. Inactivated polio vaccine(Salk) • Preferred over Oral polio vaccine only in 1. Primary immunization in adults 2. In persons with compromised immune system. • Dose: • 1ml /s.c. in the deltoid region at 4-6 week intervals (3 doses) • fourth dose is given 6-12 months later, booster doses -5 years. • Adverse effects: • Fever and local pain are common. • Allergic reactions sometimes occur
- 20. Rabies vaccine 1. Purifiedchick embryo cell vaccine (PCEV) • Flury-LEP strain of rabies virus grown on chick fibroblasts • Neuroparalytic complications have been reported rarely. • Local pain, erythema, swelling and lymph node enlargement can occur. 2. Human diploid cell vaccine (HDCV) • lyophilized inactivated rabies virus grown in human diploid cell culture • Slight induration lasting 1- 2 days occurs (10%), Fever and arthralgia (1 %) • 100% effective and well tolerated, No Vaccine associated encephalitis 3. Purified vero cell rabies vaccine (PVRV) • Contains inactivated wistar rabies strain grown on vero continuous cell line
- 21. Post exposure prophylaxisfor Rabies • Given to all non immunised animal-bite cases suspected to have been exposed to the rabies virus. • The intradermal regimen (Thai regimen): • Requires only 1/5th dose of the earlier used i.m. regimen • Less expensive, more convenient and equally efficacious. • 0.1 ml of PCEV or PVRV or 0.2 ml of HDCV injected i.d. at 2 sites (over deltoid of both arms) on days 0, 3, 7 & 28 (2 + 2 + 2+ 0 + 2). • Thus, no injection is given on day 14 as in earlier i.m. regimen • concurrent administration of rabies immunoglobulin (RIG) is recommended in category III bites
- 22. Categories of contactand recommended Post Exposure Prophylaxis (PEP) Category Description Post Exposure prophylaxis measures Category 1 • Touching or feeding animal, • Licks on intact skin None Category 2 • Nibbling of uncovered skin • Minor scratches or abrasions without bleeding Immediate vaccination and local treatment of the wound Category 3 • Single or multiple transdermal bites or scratches, licks on unbroken skin • Contamination of mucous membrane with saliva from licks • Contact with Bats Immediate vaccination and administration of rabies immunoglobin Local treatment of the wound
- 24. Hepatitis B vaccine •The new hepatitis B vaccine is prepared in yeast cells by recombinant DNA technique • Contains aluminium hydroxide adsorbed hepatitis B virus surface antigen 20 µg in 1 ml suspension. • Three I ml injections in the deltoid muscle given at 0, I and 6 months produce protective antibody titers in 99% subjects. • Children < 10 yr are given 0.5 ml doses in the thigh. L • Induration and soreness at injection site and occasional fever and malaise are the adverse effects.
- 25. Measles, Mumps, Rubella,Varicella Measles Mumps Rubella Chicken pox Rubeola Parotitis German measles Varicella Family Paramyxoviridae Family Paramyxoviridae Family Toga viridae Family orthopox virus The skin rash normally lasts about 5 to 10 days Lesions of the oral cavity include diagnostically useful Bright red Kopliks spots Mumps affects the parotid glands, salivary glands Swelling below and in front of the ears A rash of small red spots Red itchy skin rash with blisters Fever Feeling tired Headache
- 26. Mumps Vaccine • Liveattenuated vaccine prepared from mumps virus grown in cell culture of chick embryo. • A single dose of 5000 TCID50, affords protection for 10 years • Revaccination is not required. • Generally combined with measles and rubella vaccine (MMR), and is not recommended below 1 year of age. • A mild febrile reaction occurs occasionally.
- 27. Measles vaccine • Liveattenuated Vaccine grown on chick embryo • Available in single dose vials containing 1000 TCID50 of Edmonston Schwartz /Zagreb strain for s.c. injection over right deltoid region. • It produces a modified infection: fever. rash and coryza may appear after 5-10 days • Immunity lasts 8 years and no booster doses are required. • Recommended in children 9 months or older • Some protection even if given after exposure
- 28. Rubella Vaccine • Liveattenuated virus Wistar RA27/3 strain 1000 TCID50 per/ 0.5 ml inj. • It is used especially in girls from 1yr age to puberty- for immunization against German measles; mostly as combined MMR vaccine. • Contraindicated during pregnancy, febrile illness and untreated tuberculosis patients. • Reactions are fever, malaise, sore throat, joint pain & lymphadenopathy
- 33. Antisera • Purified &concentrated preparations of serum of horses/rabbits actively immunized against a specific antigen. • Adverse effects • Immediate type of allergic reactions • urticaria, angioedema, respiratory distress, anaphylaxis • Serum sickness with fever, rash, joint pain, lymphadenopathy • appears 7- 12 days later, • Frequent after large doses and repeated administration. • Local pain, erythema may occur 7-10 days after i.m. injection.
- 34. Immunoglobulins • Separated humangamma globulins which carry the antibodies • Non-specific (Normal) or specific (hyperimmune) against a particular antigen • More efficacious than antisera • Usually no hypersensitivity • Tendency increases with large and repeated dosing, adrenaline to be kept on standby
- 36. Tetanus Tetanus immune globulin(human) • Prophylaxis in non-immunized persons with contaminated wound • It is more efficacious and longer acting than the equine antitoxin (ATS). • Efficacy is variable for the treatment of clinical tetanus • Dose: prophylactic 250-500 IU therapeutic, 3000-6000 IU i.m Anti-tetanic serum (Tetanus antitoxin) • Obtained from horse and is inferior to human antitoxin. • It should be used only when tetanus immune globulin is not available • Dose: • Prophylactic 1500-3000 IU. i.m. or s.c., • Therapeutic 50,000 100.000 IU part Iv, and rest i.m.
- 37. Anti-Snake Venom Polyvalent •Purified, enzyme refined and concentrated equine globulins • Lyophilized vials with 10 ml ampoule of distilled water • After reconstitution each ml neutralizes • 0.6 mg of standard cobra venom • 0.6 mg of standard Russell's Viper venom • 0.45 mg of standard Sawscaled viper venom • 0.45 mg of standard Krait venom
- 38. Anti-snake venom Polyvalent •Dose: 20 ml i.v. (1ml/min), 1-6 hourly intervals till symptoms of envenomation disappear • 300 ml may be required in viper bites & larger amounts (upto 900 ml) have been used in cobra bites • Viper bite some serum should also be infiltrated around the site • Allergic reactions, including anaphylactic shock possible. • If possible do sensitivity test or Give adrenaline concurrently (s.c) • Antihistaminic & glucocorticoid may also be given prophylactically.
- 40. Normal Human GammaGlobulin • Concentrated immunoglobulin obtained by cold fractionation of pooled human plasma. • Indications • Viral hepatitis A and B (prophylaxis), • Measles, mumps, poliomyelitis and chickenpox • Agammaglobulinemia, leukemia, patients undergoing immunosuppression. • It can augment the response to antibiotics in debilitated patients • Dose: 0.02-1ml/kg i.m