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Overview

This section is part 7 of the PHE UK immunisation schedule.

  • Doses of different inactivated vaccines can be administered at any time before, after, or at the same time as each other. Doses of inactivated vaccines can also be given at any interval before, after, or at the same time as a live vaccine and vice versa.
  • A minimum 4-week interval is normally recommended between successive doses of the same vaccine—for example between each of the three doses of diphtheria, tetanus, and pertussis (DTaP)-containing vaccine in the primary schedule.
  • A better response is made to some vaccines (e.g. pneumococcal conjugate vaccine [PCV]) when an eight-week interval is observed between infant doses.
  • Although shorter intervals may be advised to achieve more rapid protection, e.g. for travel or during an outbreak, this may lead to a lower immune response, particularly in infants, and may therefore provide less durable protection.
  • If one of the infant primary immunisation DTaP-containing vaccine doses is inadvertently or deliberately given up to a week early (e.g. for travel) however, the impact on the final response is minimal.
  • If more than one dose in the three-dose schedule is given early, or one of the doses is given at less than a three week interval, then that dose should be repeated at least four weeks after the final dose.
  • Where infant doses of PCV or meningococcal B (MenB) are inadvertently given at an interval of less than eight weeks, an additional dose should be administered four weeks after the second dose to ensure adequate protection whilst still at a vulnerable age.
  • For other multiple dose schedules with inactivated vaccines e.g. human papillomavirus and hepatitis B, giving subsequent doses at a slightly shorter than the recommended interval is unlikely to be highly detrimental to the overall immune response, however, early vaccination should be avoided unless necessary to ensure rapid protection or to improve compliance, and additional doses may be recommended to ensure longer term protection.
  • Advice on intervals between different live vaccines is based on existing specific evidence of interference between vaccines. The current advice is detailed in the table below.
  • Recommended intervals between subsequent doses of the same live vaccine will depend upon the specific incubation period of the vaccine virus, and other factors, such as decline in maternally derived antibody. Please refer to the relevant chapters.
Table 3: Recommended time intervals when giving more than one live attenuated vaccine
Vaccine combinationsRecommendations

Yellow fever and MMR

A four week minimum interval period should be observed between the administration of these two vaccines. Yellow Fever and MMR should not be administered on the same day.*

Varicella (and zoster) vaccine and MMR

If these vaccines are not administered on the same day, then a four week minimum interval should be observed between vaccines.

Tuberculin skin testing (Mantoux) and MMR

MMR vaccination and tuberculin skin testing can be performed on the same day. However, if a tuberculin skin test has already been initiated, then MMR should be delayed until the skin test has been read unless protection against measles is required urgently. If a child has had a recent MMR, and requires a tuberculin test, then a four week interval should be observed.

All currently used live vaccines (BCG, rotavirus, live attenuated influenza vaccine (LAIV), oral typhoid vaccine, yellow fever, varicella, zoster and MMR).

Apart from those combinations listed above, these vaccines can be administered at any time before or after each other. This includes tuberculin (Mantoux) skin testing.§

* Co-administration of these two vaccines can lead to sub-optimal antibody responses to yellow fever, mumps and rubella antigens (Nascimento et. al, 2011). Where protection is required rapidly then the vaccines should be given at any interval; an additional dose of MMR should be considered.

 

A study in the US (Mullooley & Black, 2001) showed a significant increase in breakthrough infections when varicella vaccine was administered within 30 days of MMR vaccine; suggesting that MMR vaccine caused an attenuation of the response to varicella vaccine. When the vaccines are given on the same day, however, the responses have been shown to be adequate (Plotkin, Orenstein & Offit, 2013.) As the zoster (shingles) vaccine contains the same virus as varicella (chicken pox) vaccine, this recommendation has been extrapolated to MMR and zoster. Where protection from either vaccine is required rapidly then the vaccines can be given at any interval and an additional dose of the vaccine given second should be considered.

 

Administering tuberculin (Mantoux) within 28 days of MMR vaccine may result in decreased reactivity of the tuberculin and the false negative reporting of results. If tuberculin testing has already been initiated, MMR should be delayed until the skin test has been read. If protection against measles is urgently required, then the benefit of protection from the vaccine outweighs the potential interference with the tuberculin test. In this circumstance, the individual interpreting the negative tuberculin test should be aware of the recent MMR vaccination when considering how to manage that individual.

 

§ Whilst there is no evidence of decreased reactivity or interference from other live vaccines, those interpreting the results of the tuberculin skin test should be aware of any recently administered live injectable vaccines.

MMR=measles, mumps, and rubella; BCG=Bacillus Calmette-Guérin (tuberculosis)

References

Mullooly, J and Black, S (2001). Simultaneous administration of varicella vaccine and other recommended childhood vaccines – United States, 1995-1999. MMWR Weekly. Nov 30, 2001 / 50 (47); 1058 -1061. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5047a4.htm

Nascimento Silva JR, Camacho LA, Freire Mde S et al (2011). Mutual interference on the immune response to yellow fever vaccine and a combined vaccine against measles, mumps and rubella.Vaccine 29 (37): 6327- 6334

Plotkin, S. Orenstein, WA. Offit, PA (2013). Measles vaccines. Vaccines. Elsevier Saunders, China.

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full guideline available from…

www.gov.uk/government/publications/immunisation-schedule-the-green-book-chapter-11

Public Health England. UK immunisation schedule: the green book, chapter 11. April 2019.
Contains public sector information licensed under the Open Government Licence v3.0.

First included: May 2019.