Technically Speaking: Minimum Ages and Intervals Between Doses of Vaccines in a Series

Overview

Immunization providers often ask about minimum ages and minimum intervals between doses of vaccine in a series, e.g., DTaP #1 and DTaP #2. Or said another way, when is a child too young to receive a vaccine, and when is an interval too short or too long?

Immunizations are usually recommended for members of the youngest age group at risk for a disease for whom efficacy and safety of a vaccine have been demonstrated. Vaccination schedules generally are determined prior to vaccine licensure, with the spacing of doses in the clinical trial being adopted as the recommended schedule. Shorter than the recommended interval, the “minimum interval” is the shortest time between two doses of a vaccine series in which an adequate immune response to the second dose can be expected. The concern is that a dose given too soon after the previous dose may reduce the response.

Maximum intervals — they don't exist

First, let’s clear up one popular misconception; there is no such thing as a "maximum interval." With very limited exceptions (e.g., oral typhoid vaccine in certain circumstances), you do NOT need to restart a vaccine series because an interval is longer than recommended. Doses given even years later than recommended are still valid because the body has “immunologic memory.” The real problem with longer than recommended intervals is not the validity of the doses or their immunologic effect. It is that, until the series is complete, the person may remain susceptible to the associated vaccine-preventable disease.

Minimum intervals – how to use them

In contrast, maintaining minimum intervals between vaccine doses is critically important. When doses are given too close together, the body may have insufficient time to mount an immune response, and the vaccine's efficacy cannot be assured. Even though doses given at the minimum intervals are considered valid, it is preferable to maintain the longer “recommended” interval whenever possible, with a few exceptions. You should intentionally schedule patients at the minimum intervals only in certain circumstances:

• When catching up a child who starts his/her immunizations late or is more than one month behind schedule
• When a patient is scheduled to travel internationally
• You also might choose to seize the opportunity and give vaccines at the minimum intervals when a patient who is in the office is unlikely to return for recommended visits.

CDC has developed a great table generally referred to as Table 1 of the ACIP's General Recommendations(PDF) to help you determine the minimum ages and intervals for all routinely recommended vaccines.

What's the 4-day grace period?

The Advisory Committee on Immunization Practices has established one small exception to minimum intervals — "the 4-day grace period” — that allows vaccine doses administered up to four days before the minimum interval or age to be counted as valid. However, the 4-day grace period does not apply in all situations. It should not be used when scheduling future vaccination visits. It also should not be applied to the 28-day interval recommended when live parenteral vaccines are not administered at the same visit or when giving rabies vaccine. The grace period should be used primarily when reviewing historical vaccination records. Importantly, use of the grace period may be in conflict with your state’s school or child care entry requirements or with immunization registry standards, so be sure to check with your state immunization program to determine what is acceptable.

Special cases of minimum ages and intervals

Two childhood vaccines require a bit more explanation regarding scheduling:

• MMR at age 1 year — Many states’ school and childcare regulations specify that the minimum age for receipt of MMR vaccine be “on or after the first birthday,” with no allowance for a grace period. These regulations were established to help ensure that the effectiveness of this live-virus vaccine would not be compromised by the potential presence of maternal antibodies. Parents count on their providers to be sure vaccines are delivered within appropriate time frames. Be sure you are not guilty of giving the first dose of MMR even one day too early as this may lead upset parents to call your office years later when they find out their child can't start kindergarten without receiving a valid dose.
• Hepatitis B and infants — In general, the hepatitis B vaccine schedule is flexible and can vary as long as ALL of the following minimum intervals are met: at least 4 weeks are needed between doses #1 and #2, at least 8 weeks between doses #2 and #3, and at least 16 weeks between doses #1 and #3. In addition, an infant should not receive the last dose in the series earlier than age 24 weeks (168 days), or age 164 days in states that allow the 4-day grace period. Poorer immune response rates are seen in infants who complete the vaccination series prior to age 24 weeks. If the third dose is given prior to the minimum age, that dose should not be counted and should be repeated.

What if a dose is given too early?

What should a provider do if a dose was inadvertently given at too young an age or at less than the minimum interval? The dose is not considered valid and must be repeated. The repeat dose should be spaced after the invalid dose by an interval at least equal to the recommended minimum interval. In these cases, providers should be prepared to reassure parents that the extra dose of vaccine is not harmful for their child.

In short, rigorously adhering to minimum ages and intervals is vital to making certain your patients receive vaccines on a schedule that ensures vaccine effectiveness. For more information about minimum intervals and ages, consult the ACIP's General Recommendations on Immunization.(PDF)