An article published in Family Physicians Association Magazine, Rajkot

• What is the difference between vaccination and immunization?

Vaccination is the process of inoculating the vaccine/ antigen in to the body. The process of inducing immune response in the vaccine is called immunization.

• What is the difference between active and passive immunization?

Administration of vaccine through any route is called active immunization whereas administration of immunoglobulins or antiserum is called passive immunization.

• What are the differences between live attenuated and inactivated vaccines?
• Live vaccines are attenuated (modified) live organisms, which have immunogenicity i.e. can generate antibodies, but have lost pathogenecity .i.e. capability to cause the disease.  g.; OPV, measles, varicella, rubella.

Inactivated vaccines consist of

1. whole inactivated organisms g., whole cell pertussis , typhoid, rabies, IPV
2. Modified exotoxins called toxoids like diphtheria or tetanus.
3. Subunits like polysaccharide antigens in Hib and surface proteins of Hep B virus.

• Live vaccines elicit strongest antibody responses whereas non-live vaccines cannot induce a high and sustained antibody response after a single dose.
• Live vaccines can be effective in single dose but inactivated vaccines require repeated doses.

4) If live vaccines elicit strong immune response, why are they repeated?

The take of live vaccines is not 100% with the first dose. Once the vaccine has been taken up the immune response is robust and lifelong. Thus the second dose is for primary vaccine failure (no uptake of vaccine) and not for the secondary vaccine failure (decline in antibodies over time).

5) What factors determine intensity and duration of immune response?

It depends primarily on the following factors;

1. a) Nature of antigen: live vaccines are superior to killed vaccines. Exceptions are BCG and OPV.
2. b) Adjuvant: Adjuvants are agents that increase the stimulation of the immune system by enhancing antigen presentation. Aluminum salts are most often used in today’s vaccines.
3. c) Antigen dose: Immune response is better with higher antigen dose (e.g.; Hepatitis B)
4. d) Doses: Immune response improves with increasing number of doses and increasing the spacing between doses.
5. e) Age: extremes of age and disease conditions lower immune response.

6) What are limitations of young age immunization?

Maternal IgG antibodies transferred through the placenta inhibits the response to the vaccines.  They limit B cell activation, proliferation and differentiation.  However they do not affect the induction of the memory B cells and the T cell response.

7)   If maternal antibodies interfere with the neonatal immune response, why Hepatitis-B, BCG and OPV are recommended at birth?

The first dose of Hepatitis-B given at birth acts as priming dose as maternal antibodies does not interfere with the induction of the memory B cells. BCG mainly acts by inducing T cell immune response hence it can be given in the presence of the maternal antibodies. OPV is given at birth since there are no maternal IgA in the gut to neutralize the virus.

8) Why vaccines are administered at much younger age in developing countries though there are numerous limitations of young age immunization?

Since most of the childhood vaccine preventable diseases (VPDs) cause early morbidity and mortality in poor, developing countries between the ages of 1month to 12 months, there is a need to protect the children before wild organisms infect them. Protection by vaccines that would be immunogenic soon after birth would make a huge difference on the disease burden.

9) How limitations of young age immunization can be taken care of?

They can be countered by increasing the number of vaccine doses, use of adjuvant, use of boosters at a later age, and increasing the dose of vaccine antigens

10) Which is the best vaccination schedule for non-live vaccines acting on the principle of “prime-boost” mechanism?

Traditionally, 0-1-6-month schedule is considered as a most immunogenic schedule than 6-10-14months schedules for non-live T cell dependent vaccines like Hepatitis-B vaccine, since affinity maturation of B cells and formation of memory-B cell take at least 4-6 months.

Immunization schedules commencing at 2 months and having 2 months spacing between the doses are technically superior to that at 6-10-14 weeks’. However for operational reasons and for early completion of immunization and attainment of protection the later schedule is chosen in developing countries.

11) What are the implications of “immune memory” for immunization programmes?

Immune memory is seen with live vaccines/ protein antigens due to generation of memory B cells which are activated on repeat vaccination/ natural exposure. Immune memory allows one to complete an interrupted vaccine schedule without restarting the schedule. Hence immunization schedule should never be started all over again regardless of duration of interruption. 

12) Why number of doses for each vaccine is different?

Live attenuated vaccines replicate (in case of viruses) or multiply (in case of bacteria) in the body thus the number of vaccine particles increases many folds which are capable of generating antibodies in large quantity to reach seropositive levels.

On the other hand inactivated vaccines do not multiply in the body, and quantity of vaccine required to provide full protection is large. If the total quantity of vaccine is administered at the same time, fever pain, tenderness swelling may be very severe. So the quantity of vaccine is generally divided. i.e.  DPT in 3 doses and rabies in 4 or 5 doses.

13) Why do we need booster doses?

The antibody level generated after vaccination tends to decline with time. Re vaccination or booster doses are required to raise the antibody levels above the required protection levels. In most cases subclinical infection acts as a booster dose. With increased vaccination, the circulation of causative organisms declines in the community. So the chances of sub clinical exposure of disease to those immune following vaccine are reduced, thus depriving the benefit of booster effect of repeated subclinical infections. This is the reason that booster dose for varicella vaccine has been introduced in those countries where vaccine coverage is very high.

14)  Why certain vaccines are given as a single dose while some need multiple doses?

Natural infection with viral diseases provides very long or lifelong protection while infections by bacteria do not provide any long lasting protection. Second attack of measles is very rare while typhoid can recur. Similarly antibodies produced by antiviral vaccines persist for much longer period as compared to antibodies produced by antibacterial vaccines.

PS: This article was part of series of articles on practical points on vaccination in FPA times, 2013-14.

Dr Neema Sitapara

MD (Ped), PGDip. (Adolescent Pediatrics)