Immunization schedules: the rationale and ... - The INCLEN Trust

Immunization schedules: the 

rationale and tables of WHO 

recommended schedules 

Thomas Cherian 

EPI, WHO Geneva

Determinants of optimal immunization 

schedules 

• Immunological 

– Minimum age at which vaccine elicit a immune response 

– Number of doses required 

– Interval between doses, if multiple doses are required 

• Epidemiological 

– Susceptibility for infection and disease 

– Disease severity and mortality 

• Programmatic 

– Opportunity to deliver with other scheduled interventions 

– Increase coverage by limiting the required contacts 

• Safety 

2 | CHF-INCLEN Vaccinology Course, September 2011

Immunological determinants: primary 

• Primary series 

series and booster doses 

– Series of doses required for a primary response 

– Non-live vaccines usually require multiple doses for a 

satisfactory primary response – successive waves of B-cell and 

GC responses 

– Minimum of 4 weeks interval between successive doses; larger 

interval results in higher antibody levels 

• Booster doses 

– Generally 6 or more months after primary series 

– More rapid and higher Ab response; high affinity Ab 

– Longer duration of protection 


Primary and booster response 

Source: Siegrist in Vaccines eds. Plotkin, Orenstein & Offit 


Immunological determinants: vaccine and 

antigen type 

• Live versus non-live vaccines 

– Higher intensity innate response with live vaccines 

– Higher antigen content following replication and 

prolonged antigen persistence with live vaccines 

– Use of adjuvants enhance response to non-live 

vaccines 

• Antigen type 

– PS antigens T-cell independent 

• Lower Ab response of shorter duration and no 

booster response 

– Protein antigens 

• Can vary with Ag (e.g. TT > DT) and Ag dose 

Higher Ab 

Longer duration 


Immunological determinants – number of 

doses 

• Number of doses required vary by vaccine 

– In general, live vaccines induce immunity with a single dose and inactivated 

vaccines require multiple doses 

– Some live vaccines only induce immunity in a relatively small proportion of 

vaccinees, requiring multiple doses to induce immunity in an optimal % of 

population, e.g. OPV 

• Number of doses required may also vary by age 

– More doses of conjugate vaccines required in young infants 

• Duration of immunity and requirement for additional doses 

– Either to boost or to re-induce immunity (for T-cell independent antigens) 

– Non-live vaccines generally require booster doses for long term immunity 

– Since vaccines seldom produce sustained mucosal immunity, natural 

boosting from mucosal infection occurs frequently 


Immunological determinants – age & route 

of administration 

• Age 

– Maturity of the immune system 

• Inability to respond to PS antigens 

• Greater number of doses for primary response (PS-conjugate vaccines) 

– Inhibitory effect of maternal Ab 

• Route of administration 

– Most non-live vaccines have to be given IM or ID because of presence of 

adequate number of APCs 

– Mucosal immunization with non-live vaccines is difficult 

• Exception oral cholera vaccine (killed ± B subunit) 

– Route of administration less of an issue with live vaccines 

• Organisms should be able to replicate at site of administration 

• Following replication organisms disseminate and induce generalised immune 

response 


Balance between immunological and 

epidemiological determinants 

• Aim for achieving protective immune response prior to the 

age when children are most vulnerable 

– Balance between inducing reasonable protection prior to 

vulnerable age versus inducing optimal immune response 

– Starting late might induce a higher response, but miss the 

vulnerable age 

– Wider intervals between doses gives a better response, but 

delays induction of immunity, leaving children vulnerable in a 

crucial period in their life. 

• The disease epidemiology varies in different populations 

– A schedule that is used in one population is not the best for 

another; need to individualize and tailor to suit local needs 


Programmatic considerations in scheduling 

vaccination 

• Match the optimal schedules (based on immunological and 

epidemiological considerations) with programmatic 

realities in the local population to achieve maximum effect 

on disease control 

– Predominant modality of vaccine delivery, e.g. fixed sites or 

outreach, need to be considered 

– Number of contacts required with health systems 

– Explore options of linking with delivery of other interventions 

– Explore delivery mechanisms that increase coverage and reach 

the "hard to reach", e.g. campaigns, immunization days etc. 


Vaccine safety and scheduling 

• Rotavirus vaccines 

– Observed association between some live oral rotavirus vaccines 

associated and intussusception 

– Natural risk of intussusception increases with age during infancy 

– Recommendation to deliver first dose before 15 weeks and last 

dose by 32 weeks 

• Whole cell pertussis vaccine 

– Not use after 7 years of age because of increased rate of local 

reactions 


Source: WHO/V&B/02.18 


12 | CHF-INCLEN Vaccinology Course, September 2011 

Vaccination schedules 

are adapted to suit the 

local disease 

epidemiology and 

match schedules for 

other vaccines

Impact of vaccines using different 

schedules 

USA: 2,4,6 + 18 months 

The Gambia: 6, 10, 14 weeks 

Adegbola et al. Lancet 2005; 366: 144–50 


Age distribution of Hib Disease in India 

IBIS - Clinical Infectious Diseases 2002; 34:949–57 


What would be the appropriate schedule for 

pentavalent vaccine in India 

1. 6-10-14 weeks 

2. 2-4-6 months 

3. Single dose at 15 months 

4. None of the above 


% seroconvert 

100 

20 40 60 80 

0 

Proportion of Children Who Seroconvert 

After Measles Vaccination, by Age 

16 S 

| CHF-INCLEN 

Scott 

Vaccinology Course, September 2011 

>3-4 >4-5 >5-6 >6-7 >7-8 >8-9 >9-10>10-11>11-12>12-13 >13 

age at vaccination months 

Source: Source: Susan Phd Thesis Scott (Phd (Susana Thesis) Scott 

Summary of 65 published studies

Age distribution of measles cases in India 

Source: NPSP 


Age of immunization can change with 

changing epidemiology 


The current WHO 

recommended schedules

When was the first immunization schedule 

published by WHO 

1. 1948 

2. 1961 

3. 1974 

4. 1995 

5. 2010 


1961 – 1 st Schedule Published by WHO 

(Report of the technical discussions at the Thirteenth WHA) 


Background- History of WHO Recommendations 

• EPI Schedule (1974) 

– Initially included vaccines against 6 

infectious agents (BCG, DTP, OPV, 

Measles) 

• EPI Schedule Update (1995) 

– Added Yellow Fever (in endemic 

countries) and Hepatitis B to schedule 

• Current WHO Recommendations 

– >20 vaccine position papers 

– Vaccines against 9 infectious agents 

recommended for universal use in 

routine immunization programs 

• Original 6 plus Hepatitis B, Hib, 

Pneumococcal Conjugate 

WHOGPV/GEN/95.03 Rev1 


Why update the schedules 

• Increased complexity of schedules 

– Recommendations include more vaccines, age-groups and 

populations 

– Schedules need not be the same for all countries 

• Provide easy access to WHO’s recommendations 

– Consolidates recommended use of all currently recommended 

vaccines in a single document 

– Communicates the needs for expansion of the range of 

vaccines and age groups 

– Assists advisory bodies in their review of current 

recommendations to adapt/adopt for their local use 


Guiding Principles 

• Reflect existing WHO recommendations 

– Based upon WHO position papers, 1998-2008 

– No new recommendations 

• Provide flexible framework for countries to develop their 

own schedules 

• Allow for inclusion of new vaccine recommendations 


Approach 

• Table 1- Recommended routine immunizations 

– Recommendations of vaccination of all age groups 

– Illustrates vaccine recommendations across the 

lifespan, primary series and booster does 

• Table 2- Recommended routine immunization in 

children 

– Age at first dose and intervals recommended for 

childhood vaccinations 

– Similar recommendations not available for older age 

groups 


What do the tables look like

Table 1: Recommended Routine Immunization: Summary of WHO Position Papers (2008) 

Antigen 

Childhood 

(see Table 2 for details) 

Adolescent Adult Considerations 

Recommendations for all individuals 

BCG 1 1 dose Exceptions HIV 

DTP 2 

Booster (DTP) 

Booster (Td) 

Booster (Td) 

Delayed/interrupted schedule 

3 doses 

1-6 years of age 

(see footnote) 

in early adulthood or pregnancy Combination vaccine 

Categories: 

Single dose if 12-24 months of age 

Haemophilus 

influenzae type b 3 3 doses, with DTP Delayed/ interrupted schedule 

Co-administration 

Combination vaccine 

Hepatitis B 4 

3-4 doses, with DTP 

•Recommendations 

3 doses (for high-risk groups if not previously 

for 

immunized) 

all individuals Co-administration 


(see footnote for schedule options) 


Definition high-risk 

Single dose if >12 months of age 

Pneumococcal 

•Recommendations for individuals 

(Conjugate) 5 3 doses, with DTP Delayed/interrupted residing schedule in 


Polio (Oral Polio 

Vaccine-OPV) 6 3 doses, with DTP Birth dose 

certain regions 

Inactivated polio vaccine (IPV) 

Measles 7 1-2 doses (see footnote) Combination vaccine 

Recommendations for individuals residing in certain regions 

•Rotavirus vaccine is here only temporarily 

Live attenuated vaccine: 1 dose. 

Japanese 

Booster after 1 year; 

Encephalitis 8 

Mouse brain-derived vaccine: booster 

Vaccine options 

Mouse brain-derived vaccine: 2 doses. every 3 years up to 10-15 years of age 

•Recommendations for individuals in some highrisk 

populations 

Maximum age limits for 

Booster after 1 year then every 3 years 

Yellow Fever 9 1 dose, with measles Co-administration 

Rotavirus 10 

Rotarix vaccine: 2 doses; 

RotaTeq vaccine: 3 doses 

starting/completing vaccination 

Recommendations for individuals in some high-risk populations 

11 Vi vaccine: 1 dose; Ty21a vaccine: 3-4 doses. 

Definition of high-risk 

Typhoid •Recommendations for individuals receiving 

Booster dose 3-7 years after primary series 


Cholera 12 


CVD 103-HgR vaccinations vaccine: 1 dose; WC/rBS vaccine: from 2 doses immunization programs Vaccine options with 

Meningococcal 13 


1 dose 

(polysaccharide) 

certain characteristics 

Conjugate vaccine 

Hepatitis A 14 2 doses Definition of high-risk 

Rabies 15 3 doses Definition of high-risk & booster 

Recommendations for individuals receiving vaccination from immunization programmes with certain characteristics 

Mumps 16 

Coverage criteria > 80% 

2 doses, with measles 


Rubella 17 

1 dose 

1 dose (alternative strategy adolescent girls & child bearing age women) Coverage criteria > 80% 




Influenza 18 

Priority targets 

2 doses. Revaccinate annually 

1 dose from 9 years of age. Revaccinate annually 


(inactivated) 



Lower dosage for children 

Refer to http://www.who.int/immunization/documents/positionpapers/ for table and position paper updates 

This table summarizes the WHO child vaccination recommendations. It is designed to assist the development of country specific schedules, and not for health care workers. Country specific schedules 

should be based on local epidemiologic, programmatic, resource and policy considerations. While vaccines are universally recommended, some children may have contraindications to vaccination.

Table 1 Column Headings 

• Antigen 

• Childhood 

• Adolescent 

• Adult 

• Considerations 

– Draw attention to issues 

included in footnote but 

not in table 


Antigen 

Childhood 


Adolescent Adult Considerations 



DTP 2 

Booster (DTP) 

Booster (Td) 

Booster (Td) 


3 doses 




Single dose if 12-24 months of a 

Haemophilus 



Hepatitis B 4 



3 doses (for high-risk groups if not previously immunized) 





Definition high-risk 

Single dose if >12 months of ag 

Pneumococcal 

(Conjugate) 5 3 doses, with DTP Delayed/interrupted schedule 




Inactivated polio vaccine (IPV)

Table Detail 

– Recommendations in cells 

Antigen 

Table 1: Recommended Routine Immunization: Summar 

• Number of doses Childhood in primary series and booster Adolescent doses 


illustrated 


BCG 1 

DTP 2 

Haemophilus 

influenzae type b 3 

1 dose 

• Antigens with multiple vaccines are displayed where 

Booster (DTP) 

3 doses 

appropriate. 1-6 years of age 

3 doses, with DTP 

Table 1: Recommended Routine Immunization: Summar 

Childhood 

Hepatitis 

Antigen 

B 4 


3 doses (for high-risk groups if n 


Adolescent (see footno 


Recommendations Pneumococcal for all individuals 

BCG 

(Conjugate) 1 5 

3 doses, with DTP 

1 dose 

Polio 

DTP 2 (Oral Polio 

Booster (DTP) 

Booster (Td) 

Vaccine-OPV) 6 3 doses 3 doses, with DTP 



Measles 7 

1-2 doses (see footnote) 

Haemophilus 

Recommendations for individuals 

influenzae type b 3 

3 doses, residing with DTP in certain regions 


Japanese 

Booster after 1 year; 

Hepatitis Encephalitis B 4 8 

Mouse brain-derived vaccine: booster 


3 doses (for high-risk groups if n 



(see footno 


9 

Booster (Td) 

(see footnote)


Antigen 

Childhood 


Adolescent Adult Critical Issues 



DTP 2 

Booster (DTP) 

Booster (Td) 

Booster (Td) 


3 doses 




Haemophilus 



Single dose if 12-24 months of age 

Hepatitis B 4 


This table summarizes the WHO child vaccination recommendations. 



3 doses (for high-risk groups if not previously immunized) 




The ages and intervals cited are for the development of country Definition specific 

high-risk 


Pneumococcal 

(Conjugate) 5 3 doses, with DTP Delayed/interrupted schedule 

schedules, and not for health care workers. Country specific schedules 




should be based on local epidemiologic, programmatic, resource Inactivated and polio vaccine (IPV) 

Measles 7 1-2 doses (see footnote) Combination vaccine 

Recommendations policy for considerations. individuals residing in certain regions While vaccines are universally recommended, 


Japanese some children 

Booster after 

may 

1 year; 

have contraindications 

Encephalitis 8 

Mouse brain-derived vaccine: booster to vaccination. 




Yellow Fever 9 1 dose, with measles Co-administration 

Rotavirus 10 

Rotarix vaccine: 2 doses; 

Maximum age limits for 

RotaTeq vaccine: 3 doses 

starting/completing vaccination 

Recommendations for individuals in some high-risk populations 

11 Vi vaccine: 1 dose; Ty21a vaccine: 3-4 doses. 


Typhoid 

Booster dose 3-7 years after primary series 


Refer to http://www.who.int/immunization/documents/positionpapers/ 

Cholera 12 


CVD 103-HgR vaccine: 1 dose; WC/rBS vaccine: 2 doses 


Meningococcal 13 


for table and position paper updates 1 dose 

(polysaccharide) 

Conjugate vaccine 

Hepatitis A 14 2 doses Definition of high-risk 

Rabies 15 3 doses Definition of high-risk & booster 

Recommendations for individuals receiving vaccination from immunization programmes with certain characteristics 

Mumps 16 

Coverage criteria > 80% 

2 doses, with measles 


Rubella 17 

1 dose 

1 dose (alternative strategy adolescent girls & child bearing age women) Coverage criteria > 80% 




Influenza 18 


2 doses. Revaccinate annually 

1 dose from 9 years of age. Revaccinate annually 


(inactivated) 



Lower dosage for children 


This table summarizes the WHO child vaccination recommendations. It is designed to assist the development of country specific schedules, and not for health care workers. Country specific schedules 

should be based on local epidemiologic, programmatic, resource and policy considerations. While vaccines are universally recommended, some children may have contraindications to vaccination.

Antigen 

* DRAFT * Table 2: Recommended Routine Immunizations for Children: Summary of WHO Position Papers (2008) 

Recommendations for all children 

Age of 1 st Dose 

Doses in 

Interval Between Doses 

Primary 

Booster Dose 

Series 1 st to 2 nd 2 nd to 3 rd 3 rd to 4 th 

BCG 1 As soon as possible after birth 1 Exceptions HIV 

DTP 2 6 weeks (min) 3 4 weeks (min) 4 weeks (min) 

Haemophilus influenzae 

type b 3 

6 weeks (min) with DTP1, 

24 months (max) 



3 4 weeks (min) with DTP2 4 weeks (min) with DTP3 (see footnote) 

Critical Issues 

(see footnotes 

for details) 

Delayed/ interrupted schedule 



Delayed/ interrupted schedule 



Table 

Option 1 

2: Recommended 

with DTP1 3 4 weeks (min),with DTP2 4 weeks (min),with 

Routine 

DTP3 

Hepatitis B 4 Option 2 80% 


Influenza (Inactivated) 18 6 months (min) 2 1 month 

Revaccinate annually 


Abbreviations: ‘max’: maximum ‘min’: minimum 


This table summarizes the WHO vaccination recommendations for children. The ages and intervals cited are for the development of country specific schedules, and not for health care workers. Country specific 

schedules should be based on local epidemiologic, programmatic, resource and policy considerations. While vaccines are universally recommended, some children may have contraindications to vaccination.

Table 2- Column Headings 

Antigen 

* DRAFT * Table 2: Recommended Routine Immunizations for Children: Summary of WHO Position Papers (2008) 

Recommendations for all children 

Doses in 

Interval Between Doses 

Primary 

Booster Dose 

Series 1 st to 2 nd 2 nd to 3 rd 3 rd to 4 th 

BCG 1 As soon as possible after birth 1 Exceptions HIV 

DTP 2 6 weeks (min) 3 4 weeks (min) 4 weeks (min) 

Haemophilus influenzae 

type b 3 

• Antigen 

• Recommended age of 

first dose 

• Doses in primary 

series 

• Recommended 

intervals Age of 1 st Dose 

6 weeks (min) with DTP1, 

24 months (max) 



3 4 weeks (min) with DTP2 4 weeks (min) with DTP3 (see footnote) 

Option 1 with DTP1 3 4 weeks (min),with DTP2 4 weeks (min),with DTP3 

Hepatitis B 4 Option 2

Thank you!

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