Q. It is recommended that the minimum interval between two immunization sessions should be four weeks except for Anti-rabies, Japanese Encephalitis and TA vaccine. In this context, I seek a clarification on the following aspects:

1. What would be the effect if two different vaccines are administered at less than: 4 weeks interval, e.g., BCG and OPV to a newborn baby.

2. What would be the effect if the same vaccine is administered at less than 4 weeks interval, e.g., OPV as routine vaccine with or without OPT given less than 4 weeks earlier and OPV. given again on Pulse Polio Day, or if second dose of Hepatitis B vaccine is administered at less than 4 weeks interval?
 

Yash Paul,
A-D-7, Devi Marg,
Bani Park,
Jaipur 302016.
 

In the September 1997 issue of Indian Pediatrics, the intervals between doses of vaccines were discussed(1). The usual minimum interval between doses is 4 weeks, but in the cases of rabies vaccine, JE Vaccine and T A vaccine, shorter intervals are used in order to achieve quicker immunization.

To answer Dr. Yash Paul's second question first, the interval between two doses of a vaccine should ordinarily be no less than 4 weeks, but when there is a need to induce immunity rapidly, one can reduce the inter- val. In such cases, the height of immune response (e.g., antibody titer) would not be as good as what could be achieved with longer intervals. In the case of rabies vaccine, several doses are given to overcome this effect. In the case of Japanese encephalitis and typhoid fever immunization, protection during the next season of risk is obtained by the shorter interval method, but for long term protection, booster doses will be necessary. If the second dose of Hepatitis B vaccine is given at less than 4 weeks interval, the antibody level achieved after it would be lower than what would have been obtained after 4 weeks interval. However, after the third dose is given (recommended 5 months after second dose), such differences would not be much.

Two different vaccines (e.g., BCG and OPV) do not interfere between them, irrespective of how short the interval is between them. The clone of lymphocytes responding to each vaccine epitope is pre-selected and independent of each other. Therefore while one set of cells are responding to one antigen, another set can respond to another antigen without interference.

Finally, regarding OPV; unlike most other injected vaccines given in multiple doses (when each dose is a fraction of the total antigenic mass), OPV is given repeatedly for a different purpose. Each dose of OPV is the total necessary dose in the infant that responds to the 3 types of polio viruses. If there was a gap in response to one or more types (and gaps are quite common in infants in many developing countries) then the following doses are given to fill them. Therefore the principle of the 4 week-interval does not quite apply to OPV. If there is gap in infection to anyone or more serotype then the next dose, given any time, irrespective of interval, offers one more chance for infection. Some experts believe that there might be some interference to infection by one serotype while another serotype has already infected the gut; therefore they recommend 6-8 weeks interval between doses of OPV. Since several doses of OPV are given to each infant, the number of doses is a more important determinant of immune response than the interval between doses.
 

T. Jacob John,
Chairman, Immunization Committee and President Elect,
Indian Academy of Pediatrics,
Thekkekara,
2/91, Erkamalakshipuram,
Vellore 632002,
India.
 

REFERENCE

1. Paul Y, John TJ. Should we revise the primary immunization schedule? Indian Pediatr 1997; 34: 839-840.