VACCINES

• Immunity a state of relative resistance to an infection.

• Goal of immunization???

• Edward Jenner 1796 small pox vaccine first live, attenuated viral vaccine documented.

• Robert Koch 1876 demonstrated specific bacterial cause of anthrax.

• Immunity:

• Natural:• Species immunity• Individual Immunity

• Acquired:• Active Immunity• Passive Immunity

ACTIVE IMMUNITY• Antigenic stimulus production of antibodies initiates cellular

response mediated by lymphocytes and macrophages.

• Acquired in 3 ways:1. Following clinical infection• Eg: Chicken pox, Rubella, Measles

2. Following subclinical infections• Eg: Polio, Diphtheria

3. Following immunization with antigen

ACTIVE IMMUNITY• Important protective antibodies:

• Antitoxins

• Opsonins

• Lysins

• Neutralizing antibodies

• Antiadhesins

ACTIVE IMMUNITY• In case of viral diseases• Interacts with virus before initial intracellular penetration occurs.

• Prevents local replicating virus from disseminating from site of entry to target organ.

PASSIVE IMMUNITY• No antigenic stimulus• Involves transfer of preformed antibodies into recipients

• Natural: Trans placental; breast milk• Artificial:• Administration of antibodies preformed in other human (Ig)• In animals. Eg: Horses.

IMMUNE RESPONSE• PRIMARY RESPONSE

• Antigen administered for first time

• Latent period 3-10 days for antibodies to appear

• IgM titer raises in 2-3 days, reaches peak and declines

• More antigenic stimulus IgG• Imp outcome Production of memory cells by B & T lymphocytes

immunological memory

FACTORS DETERMINING NATURE, EXTENT OF PRIMARY RESPONSE

• Dose of antigen

• Nature of antigen

• Route of administration

• Adjuvants

• Nutritional status of host.

SECONDARY (BOOSTER) RESPONSE• Differs from primary response:

• Short latent period

• Rapid production of antibody

• Abundant antibody

• Maintained at higher level and for longer time

• Greater capacity to bind to antigen

• 5 recognizable types of vaccines:

• Live attenuated

• Killed

• Toxoid

• Bacterial cell component

• Viral subunit

LIVE ATTENUATED VACCINES

• Preparation of live bacteria/ virus.

• Reduced virulence.

• Single dose.

• Disadvantage:• Microbes may replicate loss of attenuation Infection.

LIVE VACCINESBACTERIAL VACCINES VIRAL VACCINES

Bacillus Calmettee Guerin (BCG)

Poliomyelitis oral live (OPV/ Sabin)

Typhoid Ty 21 a MeaslesMumpsRubellaVaricella

Yellow fever

KILLED VACCINES• Suspension of bacteria/virus killed by heat/ disinfectants

(phenol/formaldehyde)

• Do not replicate.

•Multiple doses

• Secondary immune response

KILLED VACCINESBACTERIAL VACCINES VIRAL VACCINES

Anthrax Hepatitis A and BCholera Poliomyelitis (IPV/Salk)

Typhoid- Paratyphoid Rabies Plague Japanese B encephalitis

TOXOID VACCINES• Prepared from toxins secreted by certain species of bacteria

• Toxin treated with formalin toxicity eliminated & immunogenicity is maintained.

• Formol toxins.

• Eg: Diphtheria, Tetanus

BACTERIAL CELL COMPONENT VACCINES

• Consists of only a component of bacterial cell•More specific and effective• Reduced adverse reactions• Eg:• Acellular pertussis vaccines• H. Influenza type B• N. meningitides type A & C• 23-valent pneumococcal polysaccharide.

NATIONAL IMMUNISATION SCHEDULE (according to IAP)

AGE VACCINESBIRTH BCG; OPV(0); Hep- B (1)

6 weeks DTwP (1); IPV (1); Hep- B (2); Hib (1); Rotavirus (1); PCV (1)

10 weeks DTwP (2); IPV (2); Hib (2); Rotavirus (2); PCV (2)14 weeks DTwP (3); IPV (3); Hib (3); Rotavirus (3); PCV (3)6 months OPV (1); Hep- B (3)9 months OPV (2); MMR (1)

AGE VACCINES9-12 months Typhoid Conjugate Vaccine12 months Hep- A (1)15 months MMR (2); Varicella (1); PCV booster

16-18 months DTwP/DTaP (B1); IPV (B1); Hib (B1)18 months- 2 years Hep A (2); typhoid booster

4-6 years DTwP/ DTaP (B2); OPV (3); Varicella (2); typhoid booster

10-12 years HPV

NATIONAL IMMUNISATION SCHEDULE FOR INFANTS, CHILDREN, PREGNANT WOMEN (INDIA)• For Pregnant women

VACCINE WHEN TO GIVE DOSE ROUTE SITE

TT-1 Early in Pregnancy 0.5 ml IM Upper armTT-2 4 weeks after TT-1 0.5 ml IM Upper armTT-

BoosterIf received at 2 TT doses in a pregnancy within last 3

years

0.5 ml IM Upper arm

VACCINE WHEN TO GIVE

DOSE ROUTE SITE

BCG At birth 0.1 ml (0.05 ml until 1 month age)

ID Left upper arm

Hepatitis- B At birth 0.5 ml IM Anterolateral aspect of thighOPV-0 At birth 2 drops Oral

OPV-1, 2, 3 6, 10, 14 weeks

2 drops Oral

DPT 1, 2, 3 6, 10, 14 weeks

0.5 ml IM Anterolateral aspect of thigh

Hepatitis B 1, 2, 3

6, 10, 14 weeks

0.5 ml IM Anterolateral aspect of thigh

Measles 9-12 months 0.5 ml SC Right upper arm

FOR INFANTS & CHILDREN

VACCINE WHEN TO GIVE DOSE ROUTE SITEDPT booster 16-24 months 0.5 ml IM Anterolateral

aspect of thigh

OPV booster

16-24 months 2 drops Oral

Measles (2nd dose)

16-24 months 0.5 ml SC Right upper arm

Japanese Encephalitis

16-24 months 0.5 ml SC Left upper arm

Vitamin A 16 months 2 ml OralDPT booster 5-6 years 0.5 ml IM Upper arm

TT 10 yrs & 16 yrs 0.5 ml IM Upper arm

INDIVIDUAL VACCINES

BACILLUS CALMETTE GUERIN (BCG)• Albert Calmette; Camille Guerin (1921)

• Derivative of attenuated bovine strain of tubercle bacilli.

• Danish 1331 strain (WHO)

• Jan 1967, BCG laboratory at Guindy, Chennai.

• Aim to induce a benign, artificial primary infection stimulates acquired resistance to infection with virulent tubercle bacilli reduces morbidity; mortality.

• TYPES-• Liquid (fresh) vaccine.• Freeze dried vaccine more stable.

• STABILITY-• Several weeks- ambient temperature• Upto 1 year away from light; in cool environment. Refrigerated <10 ͦ C

• Normal Saline diluent for reconstituting.

• DOSAGE: 0.1 mg in 0.1 ml; Newborn 0.05 ml

• ADMINISTRATION: Intradermal injection- Tuberculin syringe• Site: just above insertion of left deltoid muscle.

• AGE: At birth/ At 6 weeks of age

• PROTECTIVE VALUE: 15 to 20 years.

PHENOMENA AFTER VACCINATION

• 2-3 weeks Papule

• 5 weeks Papule increases 4-8mm

• Subsides/ breaks into shallow ulcer

• 6-12 weeks Heals Permanent, tiny, round scar.

POLIO VACCINE• Inactivated (Salk) polio vaccine (IPV)

• Oral (Sabin) polio vaccine

DIFFERENCE BETWEEN IPV AND OPVIPV OPV

Killed formolised virus Live attenuated virusGiven IM/SC Given orally

Induces circulating antibody; no local immunity

Both humoral and intestinal immunity

Prevents paralysis; does not prevent reinfection by wild polio viruses

Prevents paralysis and intestinal reinfection

Not useful in epidemics Effective in controlling epidemicsContent is 10,000 times more than OPV;

CostlierCheaper

Does not require stringent conditions during storage and transportation

Requires to be stored and transported at sub-zero temperature, unless stabilised

HEPATITIS B• Recombinant vaccine 1986

•Monovalent/ fixed combination (DPT, Hib, hepatitis A, inactivated polio)

• Dose 10-20 µg (adult)

• Site Deltoid/ anterolateral aspect of thigh

• National Immunisation Program at birth, 6, 10, 14 weeks

HBV in adults• Pre-exposure vaccination indications:

• Persons with high-risk sexual behaviours

• Household contacts of HBs-Ag positive persons

• Injecting drug users

• Recipients of solid organ transplantations

• Occupational risk of HBV infection

• Contraindications:• H/o allergic reactions

SEROLOGICAL TESTING IN VACCINE RECIPIENTS

• Recommended for persons with

• HBsAg prevalence 2% or more

• Sex and needle sharing contacts of HBsAg positive persons

• Homosexuals

• Injecting drug users

HEPATITIS B IMMUNOGLOBULIN (HBIG)

• Used for those exposed to HBsAg positive blood

• To be given within 6 hours

• Dose 0.05-0.07ml/kg body weight

• 2 doses 30 days apart

• Combination of HBIG and hepatitis B more efficacious than hepatitis B alone.

• Ideal for prophylaxis and prevention

• HBIG 0.05-0.07 ml/kg within 24 hrs; Hepatitis B 1 ml IM within 7 days

• 2nd dose 1 month; 3rd dose 6 months later.

DPT• National Childhood Immunisation Programme

• DPT, DTwP, DTaP vaccine

• 3 doses 0.5 ml each IM one month interval

• Given at 6 weeks, 10 weeks, 14 weeks

• Booster dose 16-18 months; 4-6 years

• DT vaccine only at 5-6 years

INFLUENZA VACCINES- KILLED• Recommended strains allantoic cavity of chick embryo

harvested purified killed by formalin/ beta-propiolactone standardized according to hemagglutinin content.

• Formulated in aqueous/ saline suspension

• Route Single dose SC/ IM

• Dose Adults; children > 3 yrs. 0.5 ml

• Children 6-36 months of age 0.25 ml

• Serum antibodies increase in 1 week; peak in 2 weeks

• Immunity 6-12 months

ROTA VIRUS VACCINE• June 5, 2009 included in all National Immunisation Programs• 2 types:

• ROTATEQ-• Pentavalent, Live• 3 doses- 2 months, 4 months, 6

months• FDA- Feb 2006

• ROTARIX-• Monovalent, live attenuated• 2 doses- 2 months, 4 months• FDA- April 2008

PNEMUOCOCCAL PNEUMONIA VACCINE

• PPV23:• Polysaccharide non-conjugate vaccine capsular antigen of 23 serotypes.• Recommended for adults and children > 2years• Indications:

• Pts undergone splenectomy

• Sickle cell disease

• Chronic disease of heart, lung, liver/ kidney

• Diabetes mellitus, alcoholism

• Generalised malignancies

• PPV23

• Dose 0.5ml 25µg of purified capsular polysaccharide

• Primary immunization Single IM (deltoid)/ SC

PNEMUOCOCCAL PNEUMONIA VACCINE

• PCV:• 2 conjugate vaccines available- PCV 10 and PCV 13• WHO recommendations:• 3 primary doses 6, 10, 14 weeks

• 2 primary+ 1 booster dose 6 weeks; interval of 4-8 weeks. Booster dose- 9-15 months.

PNEMUOCOCCAL PNEUMONIA VACCINE

MEASLES VACCINE

• Live, attenuated vaccine; Freeze dried product

• 0.5 ml contains > 1000 viral infective unit of vaccine strains

• Injected SC/ IM

• Immune response: Both cellular and humoral

MEASLES VACCINES• REACTION:

• Mild measles illness

• Occurs 5-10 days after immunization

• Fever(1-2 days) & Rash (1-3 days)

• Immunity develops 11-12 days after immunisation

RUBELLA VACCINES

• 1979 RA 27/3 Human diploid fibroblast.

• Induces higher antibody titre

• Administered single dose 0.5 ml SC

MUMPS VACCINES• Live attenuated vaccine

• Available strains Jeryl-Lynn; RIT 4385; Leningrad-3; Urabe strain etc

• Administered single dose 0.5 ml; IM

TYPHOID VACCINES• 2 vaccines licensed-

• Defined subunit antigens (Vi polysaccharide)

• Whole-cell live attenuated bacteria (Ty21a)

Vi POLYSACCHARIDE VACCINE• License- 1994, US

• Composed of purified Vi capsular polysaccharide form Ty2 strain.

• Elicits T-cell independent IgG response

• Administered SC/IM

• Single human dose- 25µg

• Stable for 6months at 37˚C; for 2 years at 22 ˚C

• Storage temperature- 2-8 ˚C

Vi POLYSACCHARIDE VACCINE

• 1 dose required.

• Confers protection after 7 days

• Revaccination recommended every 3 years to maintain

protection

• Can be co-administered with other vaccines

Ty21a VACCINE

• License- Europe (1983); USA (1989)

• Live attenuated Ty2 strain of S. Typhi

• Orally administered

• Available as enteric coated capsules

• Stable at 25˚C for 14 days.

SCHEDULE

• Age: >5 years

• 3 dose regimen: 1, 3, 5th day

• Immunity- after 7 days

• To be repeated every 3 years

•May be given with other vaccines

VARICELLA VACCINE

• Live attenuated;

• Recommended for children between 12-18 months

• 0.5 ml/ SC

• Children > 13 years 2 doses with 6 wks- 3months interval

• Combination- MMRV

HPV vaccines

• Against cervical cancer, genital warts and other cancers

• Gardasil; Cervarix Dec 2014

• 3 doses interval of 4-8 months

• 0.5 ml/IM

MENINGOCOCCAL VACCINES• Polysaccharide vaccines; Polysaccharide- protein conjugate vaccines

• Available against Meningococci of serogroup A, C, W135 and Y

• Polysaccharide vaccines: Available as:• Bivalent (A, C)• Trivalent (A, C, W 135)• Quadrivalent (A, C, W135, Y)

• Single dose; > 2 yrs of age; SC

•CONJUGATE VACCINES:

•Monovalent (A or C) or Quadrivalent (A, C, Y, W135)

• Given IM deltoid/ anterolateral aspect of upper thigh

• Children 2-11 months 2 dose at 2 months interval; booster dose after 1 year

TETANUS TOXOID• Combined vaccine- DPT

•Monovalent vaccines:

• Plain or fluid (formal) toxoid

• Tetanus vaccine, adsorbed (PTAP, APT)

MONOVALENT VACCINES

• 2 doses 0.5 ml each 1-2 months interval

• First booster dose 1 year

• Reactions after injection unlikely

PASSIVE IMMUNISATION - TETANUS• 2 Types:• Human Tetanus Hyperimmunoglobulin• ATS

• Human Tetanus Hyperimmunoglobulin• Dose: 250 IU• Passive protection upto 30 days• Serum Institute of India, Pune

ATS- Anti-tetanus Serum • Equine antitoxin

• Dose- 1500 IU; injected subcutaneously

• Passive protection for 7-10 days

• Excreted rapidly;

• Disadvantages:• Sensitivity reactions

RABIES VACCINES• 2 forms:

• Purified Cell-culture vaccine

• Embryonated egg-based vaccine

• Potency- >2.5 IU per single IM dose (0.5 ml/ 1ml, depending on type of vaccine)

CATEGORIES OF CONTACT WITH SUSPECTED RABID ANIMAL

POST-EXPOSURE PROPHYLAXIS MEASURE

Touching/ Feeding animals licks on intact skin

None

Nibbling of uncovered skin, minor scratches/ abrasions without bleeding

Immediate vaccination; Local Rx of wound

Single/ multiple transdermal bites/ scratches, Licks on broken skin;

Contamination of mucous membranes with saliva from licks;

Contacts with bats

Immediate vaccination; Administration of rabies

immunoglobulins; Local Rx of wound.

ADVERSE EVENTS FOLLOWING IMMUNISATION (AEFI’s)

• Vaccine reaction

• Programme error

• Coincidental

• Injection reaction

• Unknown

VACCINE REACTIONS• Common, minor reactions• Local• Systemic

• Rare, serious reactions

VACCINE RARE, SERIOUS REACTION ONSETBCG Suppurative Lymphadenitis 2-6 months

BCG Osteitis 1-12 months

Disseminated BCG infection 1-12 months

Hep B Anaphylaxis 0-1 hourMeasles/MMR/MR Febrile Seizures 6-12 d

Thrombocytopenia 15-35 dAnaphylaxis 0-1 hr

Encephalopathy 6-12 dOral Poliovirus Vaccine associated paralytic poliomyelitis 4-30 d

DTP Seizures 0-2 dHypotonic Hyporesponsive Episode 0-24 hr

Encephalopathy 0-2 days

PROGRAMME ERROR• Vaccine reconstituted with incorrect diluent

• Improper route of administration

• Large doses administered at once

• Contaminated vaccines

• Contraindications ignored

• Unsterilized syringes and needles

CONTRAINDICATIONSVACCINE CONTRAINDICATIONSALL Anaphylactic reaction following previous dose of particular

vaccineCurrent serious illness

Live vaccines- MMR, BCG, Yellow fever

PregnancyRadiation Therapy

Yellow fever & Influenza Egg AllergyImmunodeficiency (from medicine, disease/ symptomatic HIV infection)

BCG Symptomatic HIV infectionPertusis Containing Previous anaphylactic reaction

Uncontrolled epilepsy, Progressive encephalopathy

THE COLD CHAIN• A system of storage & transport of vaccines at low temperature

from manufacturer to actual vaccination site.

• Failure Vaccine becomes denatured and ineffective

• Vaccine Protected from sunlight and contact with antiseptics

• Polio most sensitive to heat stored at – 20 ˚C

• Freezer Polio & measles

• Not allowed to freeze typhoid, DPT, TT, DT, BCG & diluents.

• Opened multidose vials which have not been fully used should be discarded.

COLD CHAIN EQUIPMENTS

•Walk in cold rooms

• Deep freezers

• Small deep freezers & Ice Lined Refrigerators

• Cold boxes

• Vaccine carriers.

REFERENCES• Park’s text book of Preventive and Social medicine- 23rd edition.• Medical Immunology- Parslow; Stites- 10th edition• Kuby Immunology• Pharmaceutical Microbiology- Hugo & Russel- 6th edition• www.cdc.gov/vaccines• www.who.int/immunisation• Indian Academy of Pediatrics (IAP) Recommended Immunization

Schedule for Children Aged 0 through 18 Years – India, 2014 and Updates on Immunization.

THANK YOU