Vaccination

Introduction

2 Types of Vaccine

PPSV à Polysaccharide vaccine (only for high risk children) / 23 Valent / >80% cases of serious disease cover

PCV à Conjugate vaccine (for Universal immunisation) / 10, 13 valent / 49 – 88% of IPD related death cover

(PCV-7 no available, PCV-15,20 Under development)

Vaccine

PPSV– 23

PCV

PCV 13 (Prevenar)

PCV 10 (Synflorix / pneumosiil)

SEROTYPE

23 serotype - 1,2,3,4,5,6B,7F,8,

9N,9V,10A,11A112F,14,15B,17F,

18C,19F, 19A,20A,22F, 23F,33F

Capsular polyasachharide Ag of 13 Serotype– 1,3,4,5,6A,6B,7F,9V,14,

18C,19A,19F,23F

Conjugate to CRM197 (non toxic diphtheria cross reactive material carrier protein)

Capsular Polyasachharide Ag of 10 Serotype

®   Synflorix- 1,4,5,6B,7F,

9V,14, 18C,19F,23F

Conjugate to 3 different carrier protein – Tetanus toxoid, Diphtheria toxoid, non-typeable H.influenzae protein D

®   Pneumosiil-1,5,6A, 6B,7F,9V,14,19A,19F,

23F

Conjugate to CRM197 (non toxic diphtheria cross reactive material carrier protein)

IMMUNOGENECITY

Poorly immunogenic in children <2 years, doesn’t reduce nasopharyngeal carrer

Content

0.5ml / Single dose vial / 25սg of each serotype Ag

0.5ml / Single dose vial

Storage

2 to 8˚ C

2 to 8˚ C

2 to 8˚ C

DOSE

0.5 ml/ dose

0.5 ml/ dose

0.5 ml/ dose

Site & Method

IM or S/C

Anterolateral thigh or Deltoid

IM

Anterolateral thigh or Deltoid

Efficacy

T-cell independent vaccine à poorly immunogenic below 2 yr age, low memory, no heard immunity.

PPSV single dose induce serotype specific immunoglobin , also IgA.

IgG level ≥0.35սg/ml for all serotypes collectively

All PCVs comparably immunogenic with seroprotection rates of >90% following primary dose.

Safety (A/E)

Rare except

Local pain, transient fever

Rare except

Local reaction , fever, irritability à 10%

gastrointestinal symptoms à 1%

Hypersensitivity reaction, Seizure, hypotonic – hyporesponsive episode à <0.01%

Contraindication

Sever allergic reaction to prior dose

Sever allergic reaction to prior dose or any other vaccine containing diptheria toxoid as carrier protein

Schedule

NIS è

-         Not in NIS

-         Indicated only in high risk children along with PCV

-         Age group – 2 to 18 years

-         All high risk case receive PPSV after complete PCV, 8 Weeks after last dose of PCV

-         Revaccination advised after 3-5 year in high risk cases

-         Not more than 2 life time dose advised à bcz immunological HYPORESPONSIVENESS on repeted vaccination

-         PCV gradually introduced since 13/05/2017

-         Total 3 dose à 3Primary at 6, 14 weeks + 1 Booster at 9 months

-         Upper age limit – 1 year

-         PCV 10 is being used in NIS

IAP è

-         PCV 13 > PCV10 recommended

-         Total 4 dose à 3Primary at 6,10,14 weeks + 1 Booster at 12-15 month age

Catch Up è FOR PCV upto 5 years as IAP

-         <6 Month à 3 P at 4 week apart + 1 B at 12-15  month or 6 month after 3^rd dose

-         6-12 month à 2P at 4 week apart + 1B in second year

-         12-23 month à 2P at 2 month apart + no Booster

-         24-59 month à 2 dose of PCV-10 at 8 week apart or single dose PCV-13+ no BOOSTER

-         Who recommend à 2P+1 / 3P+0

-         NIS adopted à 2P+1

-         PCV -13 may be used as a single dose in high risk children (6-17 years) and adult >50 year

Special Situation

Pneumococcal immunisation of high-risk children(HRC) è

-         HRC/2-6 year age à

-         If vaccinated with 3 dose à should vaccinate with Single dose PCV13/10

-         If vaccinated with <3 dose à should vaccinate with 2 dose PC at least 8 week apart

Followed by single dose of PPSV at least 8 week apart after last dose of PCV

Followed by 2^nd dose of PPSV at least 8 week apart after last dose of PCV

-         HRC/ 6 -18 year age à

           Vaccinate with single dose of PCV 13/10

Followed by PPSV at least 8 week apart after last dose of PCV

Followed by 2^nd dose of PPSV at least 8 week apart after last dose of PCV

-         Planned splenectomy / cochlear implant / immunosuppressive therapy à

PCV – 13/10 and PPSV vaccination should be complete at least 2 week before surgery or therapy initiation

-        

FAQ

1.     Preferable vaccine?

Ans. Only PCV in healthy children / PPSV used only in high risk children, no role in healthy children / all PCV same effective / PCV13 >> PCV10 à Cover 10-15% more serotype

2.     Why PPSV-23 given as additional to PCV-13/10 vaccine in HRC ?

Ans. to expand serotype cover after routine immunisation. PPSV should never be used alone in HRC and always to be preceded with PCV recommendation dose.

3.     PCV & PPSV concurrent administration possible? Is it safe ?

Ans. not studied and not recommended, at least 8 week minimum interval required B/W both vaccine.

4.     Interchange of vaccine b/w PCV10 & 13?

Ans. not advisable, but permitted if unavoidable.

5.     PCV for Pre-term and LBW babies ?

Ans. recommended on priority based as they have 9 time higher IPD then to full term baby.

6.     Newer pneumococcal vaccine underdevelopment ?

Ans. PCV-15 = PCV-13 + (22F,33F) à Merc

PCV-20 = PCV-13 + (8,10A,11A,12F,15BC,22F,33F) à Pfizer

Also underway Serutype independent pneumococcal vaccine à

a)     Common protein based

b)    Combination (protein vaccine Ag+polysachharide conjugates)

c)     Whole cell vaccine of killed S. Pneumoniae à simultaneous present multiple surface protein Ag.

7.     Why 3 dose schedule NIS vs 4 dose schedule in IAP?

Ans. NIS à Cost consideration without compromise on efficacy

WHO à minimum 3 dose from 6 week age (2p+1B / 3p+0B)

India in NIS adopted 2P+1B schedule àBooster at 9 month to align with MR vaccine. Ab titre achieved is higher with (2 dose at 2 month interval >> 2 dose 1 month interval )

8.    

Vaccine

Type è Currently 2 Types à both active against Vi Ag

1.      TPSV à Vi Polysachharide vaccine

2.      TCV à Vi Polysachharide conjugate vaccine ( use carrier protein that boost immunogenicity)

3.      Ty21a à live attenuated / not available in INDIA

TPSV

TCV

Licensed vaccine

4 types TCV in INDIAà

-         3 conjugate with Tetanus toxoid ( Pedatyph / Zyvac-TCV / Typbar-TCV)

-         1 conjugate with Detoxified diphtheria toxin CRM 197 (Typhibev)

Content

Highly purified fraction of Vi-Capsular polysaccharide Ag

-         All TCV contain- Conjugate Vi-Ag 25սg/0.5ml

-         Except Pedatyph - 5սg/0.5ml

Immunogenicity

Poorly immunogenic in age <2 years, Does not produce immunological memory

Good immunogenic

Content

25 սg purified polysaccharide in 0.5 ml Phenolic buffer

25 սg Conjugated Vi Ag in 0.5 ml isotonic saline

Dose & administration

0.5ml/dose

Single dose vial

Intramuscular OR Deep S/C

Thigh or Deltoid region

(1ml in >18 yr age)

0.5ml/dose

Single dose vial

Intramuscular OR Deep S/C

Thigh or Deltoid region

(1ml in >18 yr age)

Age group

>2 year age

<2 year age

Storage

2 to 8 ˚C

2 to 8 ˚C with VVM

Efficacy

-         Anti-Vi Ab Titre ≥1սg/ml

Or 4X rise in titre

-         Ab titre of ≥4.3սg/ml is adequateàprotect for 4 yr

-         Reported seroconversion after 42 days of TCV is >98% in child vaccinated >6 month age

-         Ab titre wane over time

-         Immunity further boosted by subclinical natural infection

Safety

Rare except

Local pain, erythema

All TCV safe except –

Fever,

local reaction at injection site

C/I

NONE except

-         Past h/o hypersensitivity to vaccine

-         Safely give in Immunocompromised

Schedule

NIS è

Not included in NIS

Not included in NIS

IAP è

-

-         IAP recommends it

-         Single dose TCV at 6-9 month/ no Booster /

-         TCV+MMR at 9 month

Catch Up è Recommended Up to 18 years

-         Single dose of TCV to a child who received TPSV earlier.

TPSV ------------4 weeek-------àTCV

FAQ

1.     Preferred TCV  >>> TPSV ?

Ans. TCV à better immunogenicity / better protective value / longer 3-5 yr protection.

TPSVànot induce T-Cell independent immunological memory with poor anamnestic response on re-exposure

2.     Role of BOOSTER dose in TPSV ?

Ans. no use booster dose.

3.     IAP said to single dose TCV, though higher Ab titre seen with 2 dose schedule?

Ans. GMTs (Geometric mean titre) are more with 2 dose schedule >>>> 1 dose / but still no difference in seroprotection rates and protective value even after 2-3 years à so only single dose recommend.

4.     Ab titre wane after 3-5 yr of TCV, why booster no recommend?

Ans. single TCV à good GMTs and seroproetction à natural subclinical infection boost further, so no need booster dose.

5.     IAP not recommend Pedatyph, why ?

Ans. Ab titre depend on Ag dose load / pedatyph contain only 5սg/0.5ml / higher GMTs with higher Ag load/ so IAP not allow low dose vaccine.

6.     TCV protect against Paratyphoid fever ?

Ans. No / Vi locus absent from Paratyphi A, B / Not protection establish

7.     Need of vaccination inà if child has H/O confirmed Typhoid fever ?

Ans. child with H/O suspected / confirmed enteric fever must be vaccinated 4 weeks after recovery if he does not receive vaccine in last 3 year.

8.     Vaccination affects Widal test reports ?

Ans. NO, doesn’t interfere with test repory / widal test asses titre against H and O antigen / while typhoid vaccine use Purifeid Vi antigen / (earlier generation whole cell inactivated vaccine does interfere)