Mainly because little safety or efficacy data exist on doses given before 6 weeks of age, and the vaccines aren’t licensed for this use. The data that exist suggest that the response to doses given before 6 weeks is poor and, in the case of Haemophilus influenzae type b (Hib) vaccine, the response could be detrimental to the infant by possibly reducing the immune response to subsequent doses of Hib conjugate vaccine. Hepatitis B vaccine is an exception because infants respond adequately to this vaccine as early as the day of birth and receipt of this vaccine at birth is necessary to protect infants born to HBsAg-positive mothers.
Ask the Experts: Scheduling Vaccines
For routinely administered vaccines, there is no vaccine series that needs to be restarted because of an interval that is longer than recommended. In certain circumstances, oral typhoid vaccine (which may be given for international travel) needs to be restarted if the vaccine series isn’t completed within the recommended time frame.
Vaccination schedules are generally determined by clinical trials, usually prior to licensure of the vaccine. The spacing of doses in the clinical trial usually becomes the recommended schedule. A “minimum interval” is shorter than the recommended interval between doses, and is the shortest time between two doses of a vaccine series in which an adequate 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 to that dose. The minimum spacing between doses is generally included in the ACIP recommendation for that vaccine which can be found at www.cdc.gov/vaccines/hcp/acip-recs/index.html. In addition, an extensive listing of recommended and minimum intervals and ages for vaccination can be found in the ACIP “General Best Practices Guidelines for Immunization”, available at www.cdc.gov/vaccines/hcp/acip-recs/general-recs/timing.html#, Table 3-2.
The significance of non-standard intervals probably depends on the vaccine and the dose. This is a complex issue—studies have not been done to examine the effect of various intervals between doses on the immunogenicity of those doses. But ACIP has examined the available data and made recommendations about the minimum acceptable interval between doses for that dose to be considered valid (there is no maximum interval between doses). These minimum intervals are published as Table 3-2 in ACIP’s “General Best Practice Guidelines on Immunization”, available at www.cdc.gov/vaccines/hcp/acip-recs/general-recs/timing.html. Doses with a minimum interval less than the recommended minimum, as described in Table 3-2, should not be counted as valid. More details on this topic can be found in the General Best Practice Guidelines.
As a general rule, infants or children who are more than 1 month or 1 dose behind schedule should be on an accelerated schedule, which means the intervals between doses should be reduced to the minimum allowable. Catch-up schedules for children ages 4 months through 18 years are included in Table 2 of each year’s recommended immunization schedule for children and adolescents, approved by the ACIP, CDC, and all other major professional organizations of healthcare providers who care for children. To review Table 2, go to www.cdc.gov/vaccines/schedules/hcp/index.html and open the current schedule for children and adolescents.
The accelerated schedule should be used when the child is more than a month behind schedule, until you get them caught up. An accelerated schedule is acceptable as long as minimum ages and minimum intervals are observed for each dose. Once you have the child back on schedule, use the recommended ages and intervals on the childhood schedule. In this case you can give the child the first set of recommended vaccines at age 3 months and then bring him back at age 4 months and give the second set of vaccinations. At this point the child will be caught up and can return to the usual schedule. Be sure to educate the parents and talk to them about the importance of bringing the child back on time.
If a child is behind on immunizations, the Advisory Committee on Immunization Practices (ACIP) recommends using the minimum intervals between each dose until the child is caught up. The minimum interval for a vaccine can be used as many times as necessary, until the child is back on schedule. See Table 2 of the CDC Recommended Child and Adolescent Immunization Schedule, available at www.cdc.gov/vaccines/schedules/hcp/index.html.
Two or more injectable or nasally administered live vaccines not administered on the same day should be separated by at least 4 weeks to minimize the potential risk for interference. If two such vaccines are separated by less than 4 weeks, the second vaccine administered should not be counted and the dose should be repeated at least 4 weeks later. Alternatively, one can perform serologic testing to check for immunity, but this option may be more costly, may not be practical if multiple antigens are involved (such as measles, mumps and rubella), and may provide results that are difficult to interpret.
In cases where the vaccine doses given less than 28 days apart are two doses of the same live vaccine in a series (e.g., 2 doses of MMR vaccine), not different vaccines, you do not need to repeat the second dose if it was inadvertently administered within the 4-day “grace period” before day 28. If given more than 4 days earlier than day 28, the second dose should be repeated after the recommended minimum interval from the invalid dose.
The oral vaccines Ty21a typhoid, cholera and rotavirus vaccines can be administered on the same day with or at any interval before or after other live vaccines (injectable or intranasal). However, ACIP recommends that oral cholera vaccine should be administered before Ty21a vaccine, and at least 8 hours should separate the oral cholera vaccine and the first dose of Ty21a in order to minimize the risk that the oral cholera vaccine buffer might interfere with the enteric coating of the oral Ty21a vaccine.
If vaccines are given too close together, it can result in a less than optimal immune response. However, in most instances, a difference of a few days is unlikely to have a negative effect on immune response. With the exception of rabies vaccine, ACIP allows a grace period of 4 days (i.e., vaccine doses administered up to 4 days before the recommended minimum interval or age can be counted as valid). However, if a dose was administered 5 or more days earlier than the recommended minimum interval between doses, it is not valid and must be repeated. The repeat dose should be spaced after the invalid dose by the recommended minimum interval. Note that for hepatitis A vaccination, if the second dose is administered too early and must be repeated, the recommended interval between the invalid dose and the repeat dose is 6 months; however, if the repeat dose is administered earlier than 6 months no further doses are recommended as long as the interval between the first and final dose is at least 6 months.
If the first dose in a series is given 5 days or more before the recommended minimum age, the dose should be repeated on or after the date when the child reaches at least the minimum age. If the vaccine is a live vaccine, ensuring that a minimum interval of 28 days has elapsed from the invalid dose is recommended. Avoid such errors by knowing the minimum intervals and ages for routinely given vaccines. You can look up such information in the ACIP “General Best Practices Guidelines for Immunization”, available at www.cdc.gov/vaccines/hcp/acip-recs/general-recs/timing.html#, Table 3-2.
The 4-day “grace period” should not be used when scheduling future vaccination visits, and should not be applied to the 28-day interval between different live parenteral vaccines not administered at the same visit. It should be used primarily when reviewing vaccination records (for example, when evaluating a vaccination record prior to entry to daycare or school).
The “same day” generally means at the same visit. This interval has not been precisely defined and probably will never be since it would be extremely difficult to study in order to develop an evidence-based recommendation. Immunization programs (and their computer systems) likely define this differently. It seems reasonable that if two vaccines were given on the same date then they would both be valid.
For intervals of 3 months or less, you should use 28 days (4 weeks) as a “month.” For intervals of 4 months or longer, you should consider a month a “calendar month”: the interval from one calendar date to the next a month later. This is a convention that was introduced on the childhood schedule in 2002 and discussed in the paper “Evaluation of Invalid Vaccine Doses” (Stokley S, Maurice E, Smith PJ, et al. American Journal of Preventive Medicine, 2004; 26: 34–40).
In general, no. According to ACIP’s “General Best Practice Guidelines for Immunization”, concerns about spacing between doses of live vaccines not given at the same visit applies only to live injectable or intranasal vaccines. So, live oral cholera vaccine may be administered simultaneously with another vaccine, or at any interval before or after administration of another vaccine. There is one exception: ACIP recommends (based upon expert opinion) that live oral cholera vaccine should be administered at least 8 hours before the first dose of live oral Ty21a typhoid vaccine in order to minimize the risk that the oral cholera vaccine buffer might interfere with the enteric coating of the oral Ty21a vaccine.
Immunity is not considered lifetime, however, CDC does not currently have any recommendation related to revaccination with oral cholera vaccine. The duration of immunity beyond the 3-month period of clinical trial evaluation in people age 18 through 45 years following one dose is unknown. As more information becomes available, CDC will update its recommendations accordingly.
Whether these doses count as part of the child’s series depends on the intervals between these doses and the ones that preceded them. If the second MMR was separated from the previous one by at least 4 weeks, it can be counted as the second MMR. No additional doses are indicated. The 4th dose of IPV is recommended after the 4th birthday. In this case, the child would need a fifth dose of IPV on or after her fourth birthday. The fifth dose of DTaP should not be given earlier than age 4 years. Assuming this dose of DTaP was the fifth the child received, it was given too early and should not be counted. The DTaP should be repeated on or after the child’s fourth birthday.
Influenza vaccine and Td (or Tdap) may be given at the same time or at any time before or after a dose of pneumococcal polysaccharide vaccine. The only time you have to wait is when two LIVE vaccines are not given at the same visit; then you need to wait at least 4 weeks to give the second live vaccine.
LAIV can be administered at any time before or after receipt of a blood product. See www.cdc.gov/vaccines/hcp/acip-recs/general-recs/timing.html#, Table 3-5, footnote B.
Ideally, vaccination against pneumococcal disease, Hib disease, and meningococcal strains A, C, W, Y, and B should be completed at least 2 weeks before a scheduled splenectomy, if time permits. When preparing a patient for splenectomy, follow the dosing recommendations for a patient who is already asplenic.
Vaccine doses administered within the two-week period before surgery or after surgery are valid; however, administration at least two weeks before surgery ensures the patient is protected from the moment the spleen is removed. Completing all doses preoperatively requires advanced planning based on the age and vaccination history of the patient. If vaccinations cannot be completed, administer as many as feasible at least 2 weeks prior to surgery. Postponing splenectomy to complete vaccination is not recommended.
Because the most likely vaccine-preventable threat to the patient is from invasive pneumococcal disease, CDC subject matter experts consider pneumococcal conjugate vaccine (PCV) the highest priority vaccine to administer before splenectomy. This may be completed most rapidly by administering a single dose of PCV20. If PCV15 is used, a dose of pneumococcal polysaccharide vaccine (PPSV23) must be administered at least 8 weeks after PCV15. Splenectomy patients require a two-dose primary series of MenACWY, given at least 8 weeks apart. PCV may be administered at the same visit with (or any time before or after) Menveo or MenQuadfi brands of MenACWY. Because the Menactra brand of MenACWY may interfere with the immune response to PCV, if Menactra is used, the first dose of Menactra in asplenic patients should be delayed 4 weeks after PCV. The MenB primary vaccination series requires 2 doses (Bexsero, GSK) or 3 doses (Trumenba, Pfizer).
If vaccines are not administered before surgery, they should be administered as soon as the person’s condition stabilizes post-operatively.