General Recommendations on Immunization
This chapter discusses best practices related to vaccine administration, dosing, and contraindications and precautions for routinely recommended vaccines in the United States. A more thorough discussion of issues common to the use of multiple vaccines and nonroutinely recommended vaccines (rabies, smallpox, yellow fever, typhoid) can be found in the General Best Practice Guidelines for Immunization: Best Practices Guidance from the Advisory Committee on Immunization Practices. Information about non-routinely recommended travel vaccines can be found in CDC’s Yellow Book.
Timing and spacing of vaccine doses are two of the most important considerations for the appropriate use of vaccines. Specific circumstances commonly encountered in immunization practice are the timing of antibody-containing blood products and live vaccines (particularly measles- and varicella-containing vaccines), simultaneous and nonsimultaneous administration of different vaccines, and intervals between doses of the same vaccine.
Inactivated vaccines are generally not affected by circulating antibody to the antigen. Live, attenuated vaccines may be affected by circulating antibody to the antigen.
Antibody, in the form of immune globulin, might be administered simultaneously with or around the same time as a vaccination—for example, as postexposure prophylaxis for certain diseases, such as hepatitis B, rabies, and tetanus. However, the presence of circulating antibody to a vaccine antigen might reduce or eliminate the immune response to that vaccine. Specifically, some live vaccines can be affected, depending on the type of vaccine, amount of antibody, and timing of administration. Inactivated vaccines, including recombinant vaccines, are generally not affected by circulating antibody, so they can be administered before, after, or at the same time as the antibody.
Live, Injectable Vaccines
Live vaccines (also referred to as live, attenuated vaccines) must replicate to produce an immune response. Antibody against injected live-vaccine antigen may interfere with replication. If measles-mumps-rubella (MMR [MMR-II]), varicella (VAR [Varivax]), or combination measles-mumps-rubella-varicella (MMRV [ProQuad]) vaccines must be administered around the same time as antibody, the two must be separated by enough time to prevent the antibody from interfering with viral replication.
If these live vaccines are administered first, it is necessary to wait at least 2 weeks before administering the antibody. If the interval between the vaccine and antibody is less than 2 weeks, the recipient should be tested for immunity or the vaccine dose should be repeated.
If the antibody is administered first, it is necessary to wait until the antibody has waned before administering the vaccine. This will reduce the chance of interference by the antibody. A table listing the recommended intervals between administration of antibody products and any MMR or varicella-containing vaccines is included in Appendix A.
An exception to the waiting period for antibody to wane before vaccination is the low dose of RhoGam or Rhophylac (anti-Rho(D) globulin) or any other blood product administered to women who do not have evidence of immunity to rubella or varicella during the last trimester of pregnancy or at delivery. Although passively acquired antibodies can interfere with the response to rubella vaccine, the low dose of anti-Rho(D) globulin has not been demonstrated to reduce the response to the rubella vaccine. These women should receive MMR-II, Varivax, or ProQuad immediately after delivery and, if possible, be tested 3 or more months later to ensure immunity to rubella and, if necessary, to measles.
The live, injected zoster vaccine (ZVL [Zostavax]) is not known to be affected by circulating antibody and may be administered at any time before or after receipt of an antibody-containing product.
Blood Products Containing Type-Specific or Negligible Antibody
Some blood products do not contain antibodies that interfere with vaccine replication. Palivizumab (Synagis), used to prevent respiratory syncytial virus (RSV) infection in some infants and young children, contains antibody directed only at RSV. Washed red blood cells contain a negligible amount of antibody. These products can be administered at any time before or after administration of MMR or varicella-containing vaccines.
Live Oral and Intranasal Vaccines
Rotavirus vaccines (RV1 [Rotarix] and RV5 [RotaTeq]) and live, attenuated influenza vaccine (LAIV [FluMist]) are not known to be affected by the administration of immune globulin or blood products. They may be administered simultaneously with blood products or separated from them by any interval.
Almost all vaccines can be administered at the same visit.*
- PCV13 (Prevnar 13) and MenACWY-D (Menactra) should not be administered simultaneously to persons with functional or anatomic asplenia or HIV; separate these vaccines by at least 4 weeks.
- PCV13 (Prevnar 13) and PPSV23 (Pneumovax 23) should not be administered at the same visit; separate these vaccines by at least 8 weeks.
- Varicella vaccine (VAR [Varivax]) should not be administered simultaneously with smallpox vaccine.
Simultaneous Administration of Different Vaccines
Simultaneous administration of all recommended vaccines is important because it increases the probability that a child will be fully vaccinated at the appropriate age. Simultaneous administration (i.e., administration on the same day) of the most widely used live and inactivated (including recombinant) vaccines does not result in decreased antibody responses or increased rates of adverse reaction.
An exception to simultaneous administration is persons with functional or anatomic asplenia, who are at high risk for invasive pneumococcal disease. Menactra brand meningococcal conjugate vaccine is thought to interfere with the antibody response to pneumococcal conjugate vaccine (Prevnar 13). In persons 2 years of age or older, Prevnar 13 and Menactra brand should not be administered at the same visit and should be separated by at least 4 weeks. Prevnar 13 should be administered first, followed by Menactra 4 weeks later.
Live vaccines administered by the oral route (typhoid TY21a, [Vivotif], rotavirus, and adenovirus vaccines) are not believed to interfere with parenteral or intranasal live vaccines or with each other. Therefore, they may be administered simultaneously with or at any time before or after other live vaccines. However, because of the recommended immunization schedule, these vaccines are not likely to be administered simultaneously to the same child.
Combination vaccines are generally preferred over simultaneous administration of single-component vaccines. Combination vaccines contain components that can be divided equally into independently available routine vaccines and can reduce the number of injections needed. Considerations for using combination vaccines should include an assessment of the number of injections, availability of vaccine, likelihood of improved vaccination coverage, likelihood of patient return, and issues regarding storage and cost. Considerations should also include patient choice and the potential for adverse events.
There is an increased risk of febrile seizures following the first dose of the combination ProQuad vaccine compared with separate administration of MMR-II and Varivax vaccines. For the first dose, MMR-II and varicella vaccines should be administered separately for children 12 through 47 months of age unless the parent or caregiver expresses a preference for ProQuad vaccine.
Prevnar 13 and Pneumovax 23 should not be administered at the same time. Studies show adults who received Prevnar 13 simultaneously or after a dose of Pneumovax 23 had a lower antibody response to Prevnar 13 compared with adults who received Prevnar 13 without a prior dose of Pneumovax 23. However, in situations where Pneumovax 23 and Prevnar 13 are administered simultaneously in an adult, neither dose has to be repeated and both doses can count toward the lifetime total.
Nonsimultaneous Administration of Different Vaccines
If live, injected vaccines (MMR-II, ProQuad, Varivax,) and FluMist are not administered at the same visit, they should be separated by at least 4 weeks. This interval is intended to reduce or eliminate interference from the vaccine administered first with the vaccine administered later. If any two of these vaccines are administered at an interval of less than 4 weeks, then the vaccine administered second should be repeated in 4 weeks or serologic testing should be performed following MMR-II and ProQuad to confirm their effectiveness (serologic testing is not recommended following FluMist, Varivax, and Zostavax vaccines).
When both Prevnar 13 and Pneumovax 23 are indicated, Prevnar 13 should be administered first, and Pneumovax 23 should be administered either at least 8 weeks later (in persons with an immunocompromising high-risk condition, renal disease, cerebrospinal fluid [CSF] leak, or cochlear implant) or at least 1 year later (in healthy persons or persons with an immunocompetent high-risk condition). If Pneumovax 23 is inadvertently administered first, providers must wait 1 year before administering Prevnar 13. In the rare instances where Prevnar 13 is administered to an adult and only Pneumovax 23 was indicated, providers should also wait 1 year before administering Pneumovax 23.
The chart below outlines the guidance for correcting these errors.
|Infant through 1 year||Prevnar 13||Pneumovax 23 administered
|Administer Prevnar 13 ASAP|
|2 years through adolescent||Prevnar 13||Pneumovax 23 administered
|Administer Prevnar 13
8 weeks after
|2 years through adolescent||Both Prevnar 13 and
|Pneumovax 23 at same visit with Prevnar 13||Administer Prevnar 13
8 weeks after Pneumovax 23*
|2 years through adolescent||Both Prevnar 13 and Pneumovax 23||Pneumovax 23 administered first||Administer Prevnar 13
8 weeks after
|Adult||Prevnar 13 only||Pneumovax 23 administered in error||Administer Prevnar 13
1 year after
|Adult||Pneumovax 23 only||Prevnar 13 administered
1 year after Prevnar 13*
|Adult||Both Prevnar 13 and
|Pneumovax 23 administered first||Administer Prevnar 13
1 year after
|Adult||Both Prevnar 13 and
at same visit
|No action (neither dose needs to be repeated) *|
*Both doses count toward the lifetime total.
†The PCV 13 dose counts toward the lifetime total.
Interval Between Doses of the Same Vaccine
Vaccinations are recommended for the youngest age group at risk for a disease for whom vaccine efficacy and safety have been demonstrated.
Decreasing the interval between doses in a multidose vaccine series may interfere with antibody response and protection. Therefore, do not space vaccines at an interval less than the minimum interval.
Most vaccines in the immunization schedules require 2 or more doses for development of an adequate and persisting antibody response. Studies have demonstrated that following the recommended ages and intervals between doses of the same antigen(s) provides optimal protection. Table 1 in Appendix A shows the recommended and minimum ages and intervals between doses of vaccines most frequently used in the United States.
For routine vaccination, vaccine doses should not be administered at intervals less than the minimum intervals or earlier than the minimum ages. However, exceptions may occasionally be necessary.
One exception involves administering a dose up to 4 days before the minimum interval or age to avoid missing an opportunity to vaccinate. The patient may have come to the office early or may have come for an appointment not specifically for vaccination. In these situations, the provider can consider administering the vaccine earlier than the minimum interval or age. However, if the provider has confidence that the patient will return for a later visit, it is preferable to reschedule vaccination closer to the recommended interval. If the patient is new to the provider or habitually misses appointments, it may be preferable to administer the vaccine early. These early doses administered within 4 days of the minimum interval or age are considered valid. However, in certain situations, state or local requirements might mandate doses of selected vaccines be administered on or after specific ages, superseding this 4-day grace period.
Doses administered 5 days or more before the minimum interval or age should not be counted as valid and should be repeated as age-appropriate. The repeat dose should generally be spaced after the invalid dose by an interval at least equal to the recommended minimum interval shown in Table 1 of the General Best Practice Guidelines for Immunization.
Other exceptions are administering doses in a multidose vaccine series at shorter intervals than recommended when a person is behind schedule and needs to be brought up to date quickly or when international travel is pending. In these cases, an accelerated schedule using the minimum age or minimum interval criteria can be used. An example is infants 6 through 11 months of age receiving 1 dose of MMR-II (not to be counted as part of the routinely recommended series) or administering the second dose of measles vaccine before 4 years of age during a measles outbreak.
In some cases, a scheduled dose of vaccine may be administered late. A late dose should be administered at the next visit. Available data indicate intervals between doses that are longer than those routinely recommended do not affect seroconversion rate or titer when the schedule is completed. Therefore, it is not necessary to restart a series or add doses of any vaccine because of an extended interval between doses.
Vaccine Dosing–Number of Doses
For live, injected vaccines, the first dose administered at the recommended age usually provides protection. An additional dose is administered to provide another opportunity for vaccine response in the small proportion of recipients who do not respond to the first dose. For instance, approximately 95% of recipients respond to a single dose of measles vaccine. The second dose is administered to ensure that nearly 100% of persons are immune. Immunity following live vaccines is long-lasting, and booster doses are usually not necessary.
For inactivated vaccines, the first dose administered at the recommended age usually does not provide protection (hepatitis A vaccine is an exception). A protective immune response may not develop until after the second or third dose. For inactivated vaccines, antibody titers may decrease below protective levels after a few years. This phenomenon is most notable with pertussis vaccine. Tetanus and diphtheria vaccine immunity also wanes. For these vaccines, a booster dose is administered to raise antibody back to protective levels.
Not all inactivated vaccines require boosting throughout the lifetime. For example, additional doses of Hib vaccine are not required after completion of the infant primary series and booster dose because Hib disease is rare in persons older than 5 years of age. Hepatitis B vaccine does not require boosting because of immunologic memory of the vaccine and the long incubation period for hepatitis B. Immunologic memory produces an “autoboost,” which means exposure to the virus causes the established immune memory to respond faster than the virus can cause disease.
An adverse reaction or side effect is an untoward effect caused by a vaccine. An adverse reaction is different from a vaccine adverse event. Vaccine adverse event refers to any medical event that occurs following vaccination. An adverse event could be a true adverse reaction or a coincidental event, with further investigation needed to distinguish between them.
Local adverse reactions are the most common, generally occur within a few hours of the injection, and are usually mild and self-limited, such as pain, swelling, and redness at the injection site. Local reactions may occur with up to 80% of vaccine doses, depending on the type of vaccine. On rare occasions, local reactions may be exaggerated or severe. These reactions, referred to as Arthus reactions, are most frequently seen with diphtheria and tetanus toxoids. Arthus reactions are not allergic reactions. They are believed to be due to high titers of antibody, usually caused by too many doses of toxoid.
Systemic adverse reactions may occur following receipt of live, attenuated vaccines, which must replicate to produce immunity. Adverse reactions such as fever or rash following live, attenuated vaccines are similar to a mild form of the natural disease, with symptoms produced from viral replication. Systemic adverse reactions are usually mild and occur 3–21 days after the vaccine was administered (i.e., after an incubation period of the vaccine virus). FluMist differs from other live vaccines because it may cause upper respiratory symptoms (like a cold) rather than influenza-like symptoms since it replicates in the mucous membranes of the nose and throat—not in the lungs.
Systemic adverse reactions were relatively frequent with diphtheria-tetanus-whole-cell-pertussis (DTP) vaccine, which contained a whole-cell pertussis component. However, comparison of the frequency of systemic adverse events among vaccine and placebo recipients shows systemic adverse events are less common with acellular pertussis vaccine.
Allergic reactions may be caused by the vaccine antigen itself or some other vaccine component, such as cell culture material or a stabilizer, preservative, or antibiotic used to inhibit bacterial growth. Severe allergic reactions (anaphylaxis) may be life-threatening but fortunately, they are rare. The risk of an allergic reaction can be decreased by effective screening prior to vaccination. All providers who administer vaccines must have an emergency protocol, supplies, and training to treat anaphylaxis.
Reporting Vaccine Adverse Events
Providers should report any clinically significant adverse event occurring after administration of any licensed vaccine, even if they are unsure whether the vaccine caused the event, to the Vaccine Adverse Event Reporting System (VAERS). VAERS accepts reports from both the public and private sectors.
VAERSexternal icon accepts reports of adverse events through its online system. For questions or assistance with VAERS reporting, e-mail firstname.lastname@example.org or call 1-800-822-7967.
Contraindications and precautions to vaccination generally dictate circumstances when vaccines should not be administered. Many contraindications and precautions are temporary, and the vaccine can be administered later.
A contraindication is a health condition in the recipient that increases the likelihood of a serious adverse reaction to a vaccine. For instance, administering MMR-II vaccine to a person with a true anaphylactic allergy to gelatin could cause serious illness or death in the recipient. In general, vaccines should not be administered when a contraindication is present. Only four conditions are considered to be permanent contraindications.
Anaphylaxis, a severe allergy to a vaccine component, is a contraindication to any vaccine containing that component, and a severe allergy following a dose of vaccine is a contraindication to subsequent doses of that vaccine.
The other three permanent contraindications are vaccine specific.
- Encephalopathy not due to another identifiable cause and occurring within 7 days of pertussis vaccination is a contraindication to subsequent doses of pertussis-containing vaccine.
- Severe combined immunodeficiency (SCID) is a contraindication to rotavirus vaccine.
- A history of intussusception is a contraindication to rotavirus vaccine.
Two conditions are temporary contraindications to vaccination with live vaccines: pregnancy and immunosuppression.
Use of aerosolized steroids, such as inhalers for asthma, is not a contraindication to vaccination; nor are alternate-day, rapidly tapering, and short (less than 14 days) high-dose schedules, topical formulations, and physiologic replacement steroid dose schedules.
A precaution is a health condition in the recipient that might increase the chance or severity of a serious adverse reaction, might compromise the ability of the vaccine to produce immunity (such as administering measles vaccine to a person with passive immunity to measles from a blood transfusion), or might cause diagnostic confusion. Injury could result, but the chance of this happening is less than with a contraindication. In general, vaccines should be deferred when a precaution is present. However, situations may arise when the benefit of protection from the vaccine outweighs the risk of an adverse reaction, and a provider may decide to administer the vaccine.
Permanent precautions include:
- Guillain-Barré syndrome (GBS) occurring 6 weeks or less after a previous dose of a tetanus toxoid vaccine is a precaution for these vaccines.
- GBS occurring 6 weeks or less after a previous dose of influenza vaccine is a precaution for this vaccine.
- History of thrombocytopenia or thrombocytopenic purpura is a precaution for MMR vaccine.
- Chronic gastrointestinal disease, spina bifida, bladder extrophy, or altered immunocompetence other than SCID are precautions for rotavirus vaccine.
Temporary precautions include:
- Moderate or severe acute illness (all vaccines); risk-benefit decision exists until the patient is considered recovered
- Recent receipt of antibody-containing blood products (MMR-II and varicella-containing vaccines, except zoster); risk-benefit decision exists for a predefined interval
- History of Arthus-type hypersenstivity reaction after a previous dose of diphtheria toxoid or tetanus toxoid vaccine; risk-benefit decision exists until at least 10 years have elapsed since the last tetanus-toxoid-containing vaccine
- Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, progressive encephalopathy; risk-benefit decision exists until neurologic status has been clarified and stabilized
For a table showing contraindications and precautions to commonly used vaccines, see the ACIP General Best Practice Guidelines for Immunization (Table 4-1).
Family History of Adverse Events
With few exceptions, family medical history is not a contraindication or precaution to vaccines. A family history of adverse reactions unrelated to immunosuppression or family history of seizures or sudden infant death syndrome (SIDS) is not a contraindication to vaccination. However, a family history of seizures is a precaution for MMRV vaccine (ProQuad). In addition, MMR-II and varicella-containing vaccines should not be administered to persons with a history of congenital or hereditary immunodeficiency in first-degree relatives (i.e., parents or siblings), unless the potential vaccine recipient’s immunocompetence has been verified either clinically or by a laboratory.
Invalid Contraindications to Vaccination
Sometimes certain conditions or circumstances are inappropriately considered to be contraindications or precautions to vaccination. Such conditions or circumstances are known as invalid contraindications and these misperceptions result in missed opportunities to administer needed vaccines. Some of the most common invalid contraindications are mild illnesses, pregnancy and breastfeeding, allergies that are not anaphylactic in nature, and certain aspects of the patient’s family history.
Children with a mild acute illness, such as a low-grade fever, an upper respiratory infection (URI), a cold, otitis media, or mild diarrhea, should be vaccinated on schedule. Several large studies have shown that young children with these illnesses respond to measles vaccine as well as those without these conditions.
Low-grade fever is not a contraindication to vaccination. Measuring temperature is not necessary before vaccination if the patient does not appear ill and does not report currently being ill. The Advisory Committee on Immunization Practices (ACIP) has not defined a body temperature above which vaccines should not be administered. The decision to vaccinate should be based on the overall evaluation of the person rather than an arbitrary body temperature.
Moderate or Severe Acute Illness
If a person has a moderate or severe acute illness, vaccination with both live and inactivated vaccines should be delayed until the patient has recovered from the illness. There is no evidence a concurrent acute illness reduces vaccine efficacy or increases vaccine adverse events. However, the concern is an adverse event (particularly fever) following vaccination could complicate the management of a moderate or severe illness.
If an allergy to a vaccine component is not anaphylactic or not severe, it is not a contraindication to that vaccine. Only a severe allergic or anaphylactic allergy to a vaccine component is a true contraindication to vaccination.
Allergy to Products Not Present in Vaccines
There is no contraindication or precaution for persons with nonspecific allergies, duck or feather allergies, or penicillin allergy, or for persons who have relatives with allergies or those taking allergy shots. Anyone with these allergies can and should be vaccinated. No vaccine available in the United States contains duck antigen or penicillin.
Antimicrobials do not influence the immune response to most vaccines. However, antiviral drugs may affect vaccine replication in some circumstances. Live, attenuated influenza vaccine should not be administered until 48 hours after cessation of therapy using antiviral drugs (amantadine, rimantadine, zanamivir, oseltamavir, peramavir, baloxavir) that are active against influenza. If possible, antiviral drugs (acyclovir, famciclovir) that are active against herpesviruses should be discontinued 24 hours before administration of a varicella-containing vaccine.
Breastfeeding does not decrease the response to any routinely recommended childhood vaccine and is not a contraindication to vaccination.
Breastfeeding also does not extend or improve the passive immunity to vaccine-preventable disease that is provided by maternal antibody, but Hib vaccine should still be administered.
Household Contacts of Pregnant or Immunosuppressed Persons
Being a household contact of a pregnant woman or immunosuppressed person is not a contraindication to vaccination. In fact, it is critical that healthy household contacts of pregnant women and immunosuppressed persons be vaccinated. Vaccination of healthy contacts reduces the chance that pregnant women and immunosuppressed persons will be exposed to vaccine-preventable diseases.
Most routinely recommended vaccines, including live vaccines (MMR-II, Varivax, Zostavax, RotaTeq/Rotarix, and FluMist), can be administered to persons who are household contacts of pregnant or immunosuppressed persons. FluMist should not be administered to household contacts of persons who are hospitalized and in isolation because of immunosuppression.
Vaccines should be started on schedule based on the child’s chronological age. Preterm infants have been shown to respond adequately to vaccines used in infancy.
Studies demonstrate that decreased seroconversion rates might occur among preterm infants with extremely low birth weight (less than 2,000 grams) after administration of hepatitis B vaccine at birth. However, by the chronological age of 1 month, all preterm infants, regardless of initial birth weight or gestational age, are likely to respond as adequately as older and larger infants. See the chart in the “Hepatitis B” chapter for more information.
Tuberculin Skin Test
Persons who need a tuberculin skin test (TST) can and should be vaccinated. All vaccines can be administered on the same day as a TST or at any time after a TST is administered. For most vaccines, there are no TST timing restrictions.
MMR-containing vaccine may decrease the response to a TST, potentially causing a false-negative response in someone who has a tuberculosis infection. MMR-II can be administered the same day as a TST, but if MMR-II has been administered and 1 or more days have elapsed, it is recommended in most situations to wait at least 4 weeks before administering a routine TST. There is no information available on the effect of varicella-containing vaccine or FluMist on a TST. Until such information is available, it is prudent to apply the same rules for spacing measles-containing vaccine and TST to varicella-containing vaccine and FluMist.
A type of tuberculosis test known as an interferon-gamma release assay (IGRA) may be affected by live vaccines, so it is prudent to apply the same spacing rules as for TST and live vaccines.
A severe allergic reaction following a dose of vaccine will almost always be a contraindication for a subsequent dose of that vaccine. Anaphylactic reactions are those that are mediated by IgE, occur within minutes or hours of receiving the vaccine, and require medical attention. Anaphylaxis involves two or more organ systems (dermatologic, cardiovascular, respiratory, and/or gastrointestinal) simultaneously. Symptoms and signs of anaphylactic reactions are generalized urticaria (hives), swelling of the mouth and throat, difficulty breathing, wheezing, hypotension, or shock. These reactions are rare following vaccination and can often be prevented by appropriate screening.
Persons may be allergic to a vaccine antigen or to a vaccine component such as an animal protein, antibiotic, preservative, or stabilizer. A table listing vaccine contents is included in Appendix B. The most common animal protein allergen is egg protein found in influenza vaccines prepared using embryonated chicken eggs. Asking persons whether they can eat eggs without adverse effects is a reasonable way to screen for those who might be at risk if they receive egg-containing influenza vaccines. Persons with a history of egg allergy who have experienced only hives after exposure to egg should receive any recommended influenza vaccine. Influenza vaccine may also be administered to persons who report having had reactions to egg involving symptoms other than hives, such as angioedema, respiratory distress, lightheadedness, or recurrent emesis or who required epinephrine or another emergency medical intervention. The vaccine should be administered in an inpatient or outpatient medical setting and supervised by a health care provider able to recognize and manage severe allergic conditions.
A previous severe allergic reaction to influenza vaccine, regardless of the component suspected of being responsible for the reaction, is a contraindication to future receipt of the vaccine.
Studies show that children who have a history of severe allergy to eggs rarely have reactions to MMR-II and ProQuad vaccine. This is probably because measles and mumps vaccine viruses are both grown in chick embryo fibroblasts—not actually in eggs. It appears gelatin—not egg—might be the cause of allergic reactions to MMR-II. Children with egg allergies may be vaccinated with MMR-II or ProQuad without prior skin testing.
Certain vaccines contain trace amounts of neomycin. Persons who have experienced an anaphylactic reaction to neomycin should not receive these vaccines. Most often, neomycin allergy presents as contact dermatitis, a manifestation of a delayed-type (cell-mediated) immune response, rather than anaphylaxis. A history of delayed-type reactions is not a contraindication for administration of neomycin-containing vaccines.
Latex, which is sap from the commercial rubber tree, contains naturally occurring impurities (e.g., plant proteins and peptides), which are believed to be responsible for allergic reactions. The most common type of latex sensitivity is contact-type (type 4) allergy, usually resulting from prolonged contact with latex-containing gloves. Among diabetic patients, latex allergies associated with injection procedures have been described. Latex-related allergic reactions after vaccination are rare. Only one report of an allergic reaction after administration of hepatitis B vaccine to a patient with a known anaphylactic reaction to latex has been published.
If a person reports a severe allergy to latex, vaccines supplied in vials or syringes containing natural rubber should not be administered unless the benefit of vaccination clearly outweighs the risk of an allergic reaction to the vaccine. For latex allergies other than anaphylactic allergies (e.g., a history of contact allergy to latex gloves), vaccines supplied in vials or syringes containing latex can be administered.
Live-virus vaccines (e.g., MMR-II, Varivax, Zostavax, FluMist) are contraindicated during pregnancy because of the theoretical risk of virus transmission to the fetus. Sexually active young women who receive MMR-II or Varivax should be instructed to practice careful contraception for 1 month following receipt of either vaccine. On theoretical grounds, inactivated poliovirus vaccine should not be administered during pregnancy; however, it may be administered if the risk of exposure (e.g., during travel to endemic disease areas) is imminent and immediate protection is needed. HPV vaccine should not be administered to pregnant women. There is no recommendation to administer Haemophilus influenzae type b vaccine (Hib, ActHIB, Hiberix, PedvaxHIB], pneumococcal conjugate vaccine (PCV13, Prevnar 13), or serogroup B meningococcal vaccine (MenB, Bexsero, Trumenba) to a pregnant woman. Hepatitis A vaccine (HepA, Havrix, Vaqta) hepatitis B vaccine (HepB, Engerix-B, Recombivax HB), meningococcal conjugate vaccine (MenACWY, Menactra, Menveo) and pneumococcal polysaccharide vaccine (PPSV23, Pneumovax 23) should be administered to a pregnant woman if routinely recommended or if indicated.
Recommendations for vaccination of pregnant women with routinely recommended vaccines are detailed and specific to each vaccine. Details are described in each disease-specific chapter.
Live vaccines can cause severe or fatal reactions in immunosuppressed persons due to uncontrolled replication of the vaccine virus. Live vaccines should usually not be administered to severely immunosuppressed persons with congenital immunodeficiency, leukemia, lymphoma, or generalized malignancy. However, persons with isolated B-cell deficiency may receive varicella vaccine. Generally, the provider treating an immunosuppressed patient should determine the severity of that patient’s immunosuppression.
Certain drugs can also cause immunosuppression. For instance, persons receiving cancer treatment with alkylating agents, antimetabolites, or radiation therapy should not receive live vaccines. Live vaccines can be administered after chemotherapy or radiation therapy has been discontinued for at least 3 months. In addition, persons receiving large doses of corticosteroids should not receive live vaccines. This includes persons receiving 20 milligrams or more of prednisone daily or 2 or more milligrams of prednisone per kilogram of body weight per day for 14 days or longer.
The safety and efficacy of live, attenuated vaccines administered concurrently with recombinant human immune mediators and immune modulators are not known. There is evidence that use of therapeutic monoclonal antibodies, especially the anti-tumor necrosis factor (TNF) agents (e.g., adalimumab, infliximab, etanercept, golimumab, and certolizumab pegol), may lead to reactivation of latent tuberculosis infection and disease. These agents might also predispose persons to other opportunistic infections. Because these drugs vary dramatically in the scope and number of immune-system-targeted components, it is prudent to avoid administering live, attenuated vaccines while patients are taking these drugs. For vaccination against seasonal influenza, inactivated injectable alternatives are available.
The time providers should wait to administer a live-virus vaccine after immune modulator drugs have been discontinued is not specified by ACIP or other authoritative guidelines, except in the case of zoster vaccines. No basis exists for interpreting laboratory studies of immune parameters with vaccines’ safety or efficacy. Lymphocyte-depleting agents such as alemtuzumab and rituximab may cause prolonged immunosuppression. Providers should wait 6 months after administration of one of these drugs before administering any vaccine. Zoster vaccines are an exception and can be administered 1 month after discontinuing any immunomodulatory drug. (See the “Zoster” chapter for additional information on administering zoster vaccine to immunosuppressed persons.) The optimal time for restarting immunosuppressive therapy after vaccination with live vaccines has not been studied, but the Infectious Diseases Society of America (IDSA) recommends waiting at least 1 month.
Consultation with the prescribing physician (and possibly a hospital pharmacist) is recommended for management of individual patients and guidance in estimating a patient’s degree of immunosuppression.
Inactivated vaccines cannot replicate, so they are safe to use in immunosuppressed persons. Certain vaccines are recommended or specifically encouraged because immunosuppression is a risk factor for complications from certain vaccine-preventable diseases (i.e., influenza, invasive pneumococcal disease, invasive meningococcal disease, invasive Haemophilus influenzae type b disease, and hepatitis B). However, because a relatively functional immune system is required to develop an immune response to a vaccine, the immune response may be poor, depending on the degree of immunosuppression present. Additional recommendations for vaccination of immunosuppressed persons are detailed in ACIP’s General Best Practice Guidelines for Immunization.
Persons infected with human immunodeficiency virus (HIV) may not manifest disease, or they may be severely immunosuppressed. In general, the same vaccination recommendations apply as for other types of immunosuppression. Live-virus vaccines are usually contraindicated in those with severe immunosuppression, but inactivated vaccines may be administered if indicated.
For persons infected with HIV:
- Varivax can be considered for persons who are not severely immunocompromised, since varicella infection can be severe for HIV-positive persons and is often associated with complications.
- MMR-II vaccine should be administered to persons who are not severely immunocompromised.
- Zoster vaccines should not be administered to persons with AIDS or clinical manifestations of HIV infection.
- FluMist should not be administered, but inactivated influenza vaccine (IIV) should be administered.
Hematopoietic Cell Transplant Recipients
Hematopoietic cell transplant (HCT) recipients should receive certain routinely recommended vaccines because antibody titers decline 1 to 4 years after HCT. HCT recipients at increased risk should be routinely vaccinated after HCT against tetanus, poliovirus, measles, mumps, rubella, Streptococcus pneumoniae, and Haemophilus influenzae type b, regardless of the source of the transplanted cells. Specifically:
- MMR and varicella-containing vaccines should be administered 24 months after transplantation if the HCT recipient is presumed to be immunocompetent.
- Revaccination with inactivated vaccines, including influenza vaccine, should begin 6 months after HCT. However, influenza vaccine may be administered as early as 4 months after HCT, if needed.
- Three doses of Prevnar 13 should be administered 6 months after HCT, followed by a dose of PPSV23.
- A dose of MenACWY should also be administered 6 months after HCT.
The key to preventing serious adverse reactions is effective screening. Every patient should be screened for contraindications and precautions before administering any vaccine dose. Effective screening can be accomplished by asking a few questions:
Is the patient sick today?
There is no evidence that acute illness reduces vaccine efficacy or increases vaccine adverse events. However, as a precaution, if there is a moderate or severe acute illness, all vaccines should be deferred until the illness has improved. Mild illnesses (such as otitis media, upper respiratory infections, and diarrhea) are not contraindications or precautions to vaccination and recommended vaccines should be administered on time.
Does the patient have allergies to medications, food, a vaccine component, or latex?
It may be more efficient to inquire about allergies in a generic way (i.e., allergies to any food or medication) rather than to inquire about specific vaccine components. Most persons will not be familiar with minor components of vaccines, but they should know if they or their child have had an allergic reaction to a food or medication that was severe enough to require medical attention. If a person reports anaphylaxis after eating eggs, a specific protocol should be followed that includes determining the symptoms experienced. For specific information on dealing with egg allergies, see the “Allergies” section or the “Influenza” chapter.
Has the patient experienced a serious reaction after receiving a vaccination?
A history of severe allergic reaction such as hives (urticaria), wheezing or difficulty breathing, or circulatory collapse or shock (not fainting) following a previous dose of vaccine or to a vaccine component is a contraindication to further doses.
Usually vaccines are deferred when a precaution is present. However, situations may arise when the benefit outweighs the risk (e.g., during a community pertussis outbreak). A local reaction (redness or swelling at the injection site) is not a contraindication to subsequent doses.
Has the patient experienced a seizure or a brain or other nervous system problem?
DTaP and Tdap are contraindicated for children who have a history of encephalopathy not attributed to an identifiable cause within 7 days following DTaP, DTP, or Tdap vaccination. An unstable or progressive neurologic problem is a precaution for the use of DTaP and Tdap. Children with stable neurologic disorders (including seizures) unrelated to vaccination may be vaccinated as usual.
A history of GBS is a precaution for tetanus-containing and influenza vaccines, if it occurred within 6 weeks following a dose of the specific vaccine.
Patients with a personal or family history of febrile or afebrile seizures have a precaution for ProQuad vaccine. Simultaneous administration of MMR-II and Varivax is not associated with an increased risk of fever or seizures and is, therefore, preferred to ProQuad.
Does the patient have a long-term health problem with heart, lung, kidney, or metabolic disease (e.g., diabetes), asthma, a blood disorder, no spleen, complement component deficiency, a cochlear implant, or a CSF leak? Is the patient on long-term aspirin therapy?
These conditions are contraindications or precautions to LAIV or conditions for which LAIV is not recommended. Inactivated influenza vaccine is preferred for patients with these conditions.
Does the patient have cancer, leukemia, HIV/AIDS, or any other immune system problem?
Live-virus vaccines (e.g., MMR-II, Varivax, Rotarix and RotaTeq, and FluMist) are usually contraindicated in severely immunocompromised persons. However, there are exceptions. For example, MMR-II and Varivax are recommended for HIV-infected children who do not have evidence of severe immunosuppression. For details, consult the individual disease chapters and the ACIP recommendations for each vaccine.
Has the patient taken medications that affect the immune system, such as prednisone, other steroids, or anticancer drugs; drugs for the treatment of rheumatoid arthritis, Crohn’s disease, or psoriasis; or has the patient had radiation treatment?
Live-virus vaccines (e.g., MMR-II, Varivax, Zostavax, FluMist) should be postponed until after chemotherapy or long-term, high-dose steroid therapy has ended. Details and the length of time to defer vaccination are described elsewhere in this chapter, in the individual disease chapters, and in the ACIP General Best Practice Guidelines for Immunization.
Has the patient received a transfusion of blood or blood products, immune (gamma) globulin, or an antiviral drug in the past year?
Certain live-virus vaccines (i.e., MMR-II, MMRV, and Varivax) may need to be deferred following administration of blood products, depending on the type of blood product and the interval since the blood product was administered. Information on recommended intervals between administration of immune globulin or blood products and MMR-II or Varivax is in Appendix A and in the ACIP General Best Practice Guidelines for Immunization.
Is the person pregnant or is there a chance she could become pregnant during the next month?
Live-virus vaccines (e.g., MMR-II, Varivax, Zostavax, FluMist) are contraindicated during pregnancy because of the theoretical risk of virus transmission to the fetus. Sexually active young women who receive MMR-II or Varivax should be instructed to practice careful contraception for 1 month following receipt of either vaccine. On theoretical grounds, inactivated poliovirus vaccine should not be administered during pregnancy; however, it may be administered if the risk of exposure (e.g., during travel to endemic disease areas) is imminent and immediate protection is needed. HPV vaccine should not be administered to pregnant women. There is no recommendation to administer Haemophilus influenzae type b vaccine (Hib, ActHIB, Hiberix, PedvaxHIB], pneumococcal conjugate vaccine (PCV13, Prevnar 13), or serogroup B meningococcal vaccine (MenB, Bexsero, Trumenba) to a pregnant woman. Hepatitis A vaccine (HepA, Havrix, Vaqta), hepatitis B vaccine (HepB, Engerix-B, Recombivax HB), meningococcal conjugate vaccine (MenACWY, Menactra, Menveo), and pneumococcal polysaccharide vaccine (PPSV23, Pneumovax 23) should be administered to pregnant women if routinely recommended or indicated.
Has the patient received vaccinations in the past 4 weeks?
A person who received either live, attenuated influenza vaccine or an injectable live-virus vaccine (e.g., MMR-II, Varivax) in the past 4 weeks should wait 28 days before receiving another live vaccine. Inactivated vaccines may be administered at the same time or at any time before or after a live vaccine.
- American Academy of Pediatrics. Active and passive immunization. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics;2018:13-–64.
- CDC. General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices. MMWR 2011;60(No. RR-2):1–61.
- Dietz VJ, Stevenson J, Zell ER, et al. Potential impact on vaccination coverage levels by administering vaccines simultaneously and reducing dropout rates. Arch Pediatr Adolesc Med 1994;148:943–9.
- Ezeanolue E, Harriman K, Hunter P, Kroger A, Pellegrini C. General Best Practice Guidelines for Immunization: Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP)pdf icon. Accessed December 27, 2019.
- Jackson BR, Iqbal S, Mahon B. Updated Recommendations for the Use of Typhoid Vaccine—Advisory Committee on Immunization Practices, United States, 2015. MMWR 2015; 64:305–308.
- James JM, Burks AW, Roberson RK, Sampson HA. Safe administration of the measles vaccine to children allergic to eggs. N Engl J Med 1995;332:1262–9.
- King GE, Hadler SC. Simultaneous administration of childhood vaccines: an important public health policy that is safe and efficacious. Pediatr Infect Dis J 1994;13:394–407.
- Kroger AT, Atkinson WL, Pickering LK. General immunization practices. In: Plotkin SA, Orenstein WA, Offit PA, Edwards KM, eds. Plotkin’s Vaccines. 7th ed. Philadelphia, PA: Elsevier; 2018.
- Rubin L, Levin M, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58(3):e44–100.
- Plotkin SA. Vaccines, vaccination and vaccinology. J. Infect Dis 2003;187:1349–59.
- Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective. Biol Blood Marrow Transplant 2009;15:1143–1238.
- Wood, RA, Berger M, Dreskin M, et al. An algorithm for treatment of patients with hypersensitivity reactions after vaccines. Pediatrics 2008;122(No. 3):e771–7.