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Overview of Immunization

by William D. Surkis, MD, Jerome Santoro, MD

Immunity can be achieved

  • Actively by using antigens (eg, vaccines, toxoids)

  • Passively by using antibodies (eg, immune globulins, antitoxins)

A toxoid is a bacterial toxin that has been modified to be nontoxic but that can still stimulate antibody formation.

A vaccine is a suspension of whole (live or inactivated) or fractionated bacteria or viruses rendered nonpathogenic. For vaccines available in the US, see Table: Vaccines Available in the US.

The most current recommendations for immunization are available at the Centers for Disease Control and Prevention (CDC) web site and as a free mobile app . Also see Table: Recommended Immunization Schedule for Ages 0–6 yr, Recommended Immunization Schedule for Ages 7–18 yr (see also the CDC's Childhood Immunization Schedule ), and Vaccine Administration Guidelines for Adults. For the contents of each vaccine (including additives), see that vaccine's package insert.

Vaccination has been extremely effective in preventing serious disease and in improving health worldwide. Because of vaccines, infections that were once very common and/or fatal (eg, smallpox, polio, measles, diphtheria) are now rare or have been eliminated. However, these infections still occur in parts of the developing world.

Effective vaccines are not yet available for many important infections, including

  • Most sexually transmitted diseases (eg, HIV, herpes, syphilis, gonorrhea, chlamydial infections)

  • Tick-borne infections (eg, Lyme disease, ehrlichiosis and anaplasmosis, babesiosis)

  • Many tropical diseases (eg, malaria, Chikungunya disease, dengue)

  • Emerging diseases (eg, Ebola hemorrhagic fever, West Nile virus infection)

Certain vaccines are recommended routinely for all adults at certain ages who have not previously been vaccinated or have no evidence of previous infection. Other vaccines (eg, rabies, BCG, typhoid, yellow fever) are not routinely given but are recommended only for specific people and circumstances (see the Centers for Disease Control and Prevention’s [CDC's] Recommended Adult Immunization Schedule and under the specific disorder, elsewhere in T he M anual ).

Some adults do not get the vaccines recommended for them. For example, only 55.1% of those > 65 were given a tetanus vaccine within a 10-yr period. Also, vaccination rates tend to be lower in blacks, Asians, and Hispanics than in whites.

Vaccines Available in the US

Vaccine

Type

Route

Inactivated bacteria

sc

BCG (for tuberculosis)

Live Mycobacteria bovis

Intradermal or sc

Toxoids and inactivated bacterial components

IM

DTaP plus Haemophilus influenzae type b conjugate ( DTaP-Hib )

Toxoids, inactivated whole bacteria, and bacterial polysaccharide conjugated to protein

IM

DTaP-hepatitis B-polio ( DTaP-HepB-IPV )

Toxoids, recombinant viral antigen, and inactivated poliovirus

IM

Toxoids, inactivated bacteria, and inactivated poliovirus

IM

Toxoids, inactivated bacteria, inactivated poliovirus, and bacterial polysaccharide conjugated to protein

IM

Haemophilus influenzae type b conjugate ( Hib )

Bacterial polysaccharide conjugated to protein

IM

Hepatitis A ( HepA )

Inactivated virus

IM

Hepatitis B ( HepB )

Recombinant viral antigen

IM

Hepatitis A and hepatitis B

Inactivated virus plus recombinant viral antigens

IM

HbCV plus Hep B

Bacterial polysaccharide conjugate plus inactivated viral antigen

IM

Human papillomavirus ( HPV )

Noninfectious viruslike particles

IM

Live influenza A and B virus

Intranasal

Influenza, types A and B

Inactivated virus or viral components

IM or intradermal

Inactivated virus

sc

Measles-mumps-rubella ( MMR )

Live viruses

sc

Measles-mumps-rubella-varicella (MMRV)

Live viruses

sc

Meningococcal , polysaccharide (MPSV4)

Bacterial polysaccharides of serogroups A/C/Y/W-135

sc

Meningococcal, conjugate (MenACWY)

Bacterial polysaccharides of serogroups A, C, Y, and W-135 conjugated to diphtheria toxoid protein

IM

Meningococcal group B (MenB)

Recombinant vaccine composed of two LP2086 antigens (factor H–binding proteins)

IM

Pneumococcal , polysaccharide (PPSV23)

Bacterial polysaccharides of 23 pneumococcal types

IM or sc

Pneumococcal, conjugate (PCV13)

Polysaccharides of 13 types, conjugated to diphtheria toxin

IM

Poliovirus ( IPV )

Inactivated viruses of all 3 serotypes

IM

Inactivated virus

Intradermal* or sc

Live virus

Oral

Live vaccinia virus

Intradermal via multiple puncture device

Inactivated toxin (toxoid)

IM

Tetanus and diphtheria toxoids adsorbed (Td) or diphtheria-tetanus (DT)

Inactivated toxins (toxoids)

IM

Tuberculosis (see BCG)

Capsular polysaccharide

IM

Typhoid

Live-attenuated vaccine

po

Live virus

sc

Zoster ( shingles )

Live virus

sc

Live virus

sc

*Intradermal dose is lower and used only for preexposure vaccination.

Preparations with adjuvants should be given IM.

Td contains the same amount of tetanus toxoid as DTP or DT but a reduced dose of diphtheria toxoid.

Modified from the Vaccine Recommendations of the Advisory Committee for Immunization Practices ( ACIP ). Accessed 12/11/14.

Vaccine Administration

For more information about vaccine administration, see the CDC's Vaccine Administration .

Vaccines should be given exactly as recommended on the package insert; however, for most vaccines, the interval between a series of doses may be lengthened without losing efficacy.

Injection vaccines are usually given IM into the midlateral thigh (in infants and toddlers) or into the deltoid muscle (in school-aged children and adults). Some vaccines are given sc. For details on vaccine administration, see Vaccination Administration: Recommendations and Guidelines and Administering Vaccines to Adults .

Clinicians should have a process in place to ensure that patient vaccination status is reviewed at each visit so that vaccines are given as per recommendations. Patients (or caregivers) should be encouraged to keep a history (written or electronic) of their vaccinations and share this information with new health care practitioners and institutions to make sure that vaccinations are up to date.

Pearls & Pitfalls

  • If a vaccine series is interrupted, practitioners should give the next recommended dose the next time the patient presents, provided that the recommended interval between doses has passed; they should not restart the series (ie, with dose 1).

If a vaccine series (eg, for hepatitis B or human papillomavirus) is interrupted, practitioners should give the next recommended dose the next time the patient presents, provided that the recommended interval between doses has passed. They should not restart the series (ie, with dose 1).

Vaccine Administration Guidelines for Adults

Parameter

Needle Size

Comments

By route

sc

23–25 gauge

5/8" long

The needle should be inserted into fatty tissue over the triceps.

IM

23–25 gauge for injection into the deltoid

Needle length is determined by sex and weight (see below).

By sex and weight for IM injection

Male or female, < 60 kg

5/8–1" long

A 5/8" needle may be used for IM injection in the deltoid muscle only if subcutaneous tissue is not bunched and injection is made at a 90° angle.

Females, 60–90 kg

1-1.5" long

Males, 60–118 kg

1–1.5" long

Females, > 90 kg

1.5" long

Males, > 118 kg

1.5" long

Simultaneous administration of different vaccines

With rare exceptions, simultaneous administration is safe, effective, and convenient (see Use of multiple, simultaneous vaccines); it is particularly recommended when children may be unavailable for future vaccination or when adults require multiple simultaneous vaccines (eg, before international travel). An exception is simultaneous administration of pneumococcal conjugate vaccine (PCV13) and the meningococcal conjugate vaccine MenACWY-D (Menactra®) to children with functional or anatomic asplenia; these vaccinations should not be given during the same visit but should be separated by ≥ 4 wk.

Simultaneous administration may involve combination vaccines (see Table: Vaccines Available in the US) or use of 1 single-antigen vaccines. More than one vaccine may be given at the same time using different injection sites and syringes.

If live-virus vaccines (varicella and MMR) are not given at the same time, they should be given ≥ 4 wk apart.

Restrictions, Precautions, and High-Risk Groups

Restrictions and precautions are conditions that increase the risk of an adverse reaction to a vaccine or that compromise the ability of a vaccine to produce immunity. These conditions are usually temporary, meaning the vaccine can be given later. Sometimes vaccination is indicated when a precaution exists because the protective effects of the vaccine outweigh the risk of an adverse reaction to the vaccine.

Contraindications are conditions that increases the risk of a serious adverse reaction. A vaccine should not be given when a contraindication is present.

Allergy

For many vaccines, the only contraindication is a serious allergic reaction (eg, anaphylactic reaction) to the vaccine or to one of its components.

Egg allergy is common in the US. Some vaccines produced in cell culture systems, including most influenza vaccines (see also Influenza Vaccine), contain trace amounts of egg antigens; thus, there is concern about using such vaccines in patients who are allergic to eggs. CDC guidelines for the influenza vaccine state that although mild reactions may occur, serious allergic reactions (ie, anaphylaxis) are unlikely, and vaccination with inactivated influenza vaccine is contraindicated only in patients who have had anaphylaxis after a previous dose of any influenza vaccine or to a vaccine component, including egg protein. Live influenza vaccine is not recommended for patients with a history of any egg allergy. Patients with a history of less severe reactions to eggs (eg, hives) may be given an egg-prepared, inactivated influenza vaccine provided the clinician has experience managing allergic reactions and observes the patient for 30 min after vaccination.

Asplenia

Asplenic patients are predisposed to overwhelming bacteremic infection, primarily due to encapsulated organisms such as Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae type b (Hib). Asplenic adults should be given the following vaccines (before splenectomy if possible):

  • Hib conjugate vaccine (HbCV): A single dose and no booster

  • Meningococcal conjugate vaccine (MenACY—see Meningococcal Vaccine): 2 doses 8 to 12 wk apart and boosters every 5 yr

  • Pneumococcal conjugate (PCV13) and polysaccharide vaccines (PPSV23): PCV13 if patients did not receive a full series previously as a routine vaccination, then PPSV23 8 wk later (≥ 2 wk before or after splenectomy) with a single PPSV23 booster after 5 yr and a routine booster dose at age 65 (see Pneumococcal Vaccine)

Additional doses may be given based on clinical judgment.

Blood product use

Live-microbial vaccines should not be given simultaneously with blood or plasma transfusions or immune globulin; these products can interfere with development of desired antibodies. Ideally, live-microbial vaccines should be given 2 wk before or 6 to 12 weeks after the immune globulins.

Fever or other acute illness

A significant fever (temperature of > 39°C) or severe illness without fever requires delaying vaccination, but minor infections, such as the common cold (even with low-grade fever), do not. This precaution prevents confusion between manifestations of the underlying illness and possible adverse effects of the vaccine and prevents superimposition of adverse effects of the vaccine on the underlying illness. Vaccination is postponed until the illness resolves, if possible.

Guillain-Barré syndrome

Patients who developed Guillain-Barré syndrome (GBS) within 6 wk after a previous influenza or DTaP vaccination may be given the vaccine if the benefits of vaccination are thought to outweigh the risks. For example, for patients who developed the syndrome after a dose of DTaP, clinicians may consider giving them a dose of the vaccine if a pertussis outbreak occurs; however, such decisions should be made in consultation with an infectious disease specialist.

The Advisory Committee on Immunization Practices (ACIP) no longer considers a history of GBS to be a precaution for use of the meningococcal conjugate vaccine, although it remains listed as a precaution in the package insert.

Immunocompromise

Immunocompromised patients should, in general, not receive live-virus vaccines, which could provoke severe or fatal infections. If immunocompromise is caused by immunosuppressive therapy (eg, high-dose corticosteroids [≥ 20 mg prednisone or equivalent for ≥ 2 wk], antimetabolites, immune modulators, alkylating compounds, radiation), live-virus vaccines should be withheld until the immune system recovers after treatment (the interval of time varies depending on the therapy used). For patients receiving long-term immunosuppressive therapy, clinicians should discuss risks and benefits of vaccination and/or revaccination with an infectious disease specialist.

Patients with HIV infection should generally receive inactivated vaccines (eg, diphtheria-tetanus-acellular pertussis [Tdap], polio [IPV], Hib) according to routine recommendations. Despite the general caution against giving a live-virus vaccine, patients who have CD4 counts ≥ 200/μL (ie, are not severely immunocompromised) can be given certain live-virus vaccines, including measles-mumps-rubella (MMR). Patients with HIV infection should receive both pneumococcal conjugate and polysaccharide vaccines (and be revaccinated after 5 yr).

Live-virus vaccines

Live-microbial vaccines should not be given simultaneously with blood, plasma, or immune globulin, which can interfere with development of desired antibodies; ideally, such vaccines should be given 2 wk before or 6 to 12 wk after the immune globulins.

Pregnancy

Pregnancy is a contraindication to vaccination with MMR, intranasal (live) influenza vaccine, varicella, and other live-virus vaccines. Vaccination with HPV vaccine is not recommended (see Overview of Immunization : Restrictions, Precautions, and High-Risk Groups).

Transplantation

Before solid organ transplantation, patients should receive all appropriate vaccines. Patients who have had allogeneic or autogeneic hematopoietic stem cell transplantation should be considered unimmunized and should receive repeat doses of all appropriate vaccines. Care of these patients is complex, and vaccination decisions for these patients should involve consultation with the patient's hematologist-oncologist and an infectious disease specialist.

Vaccine Safety

In the US, the safety of vaccines is ensured through several surveillance systems; selected events that occur after routine vaccination must be reported by mail, by fax, or electronically to the CDC's Vaccine Adverse Event Reporting System [ VAERS ], Vaccine Safety Datalink [ VSD ]—see Effectiveness and Safety of Childhood Vaccination). For additional information about the safety of individual vaccines, see Vaccine Safety at the CDC web site.

Nonetheless, many parents remain concerned about the safety and possible adverse effects (particularly autism) of childhood vaccines. These concerns, perpetuated on the Internet, have led some parents to not allow their children to be given some or all of the recommended vaccines (see Anti-Vaccination Movement). As a result, outbreaks of diseases made uncommon by vaccination (eg, measles, pertussis) are becoming more common among unvaccinated children in North America and Europe.

One of the main parental concerns is that vaccines may increase the risk of autism. Reasons cited include

In 1998, Andrew Wakefield and colleagues published a brief report in The Lancet (see MMR vaccine and autism). In it, Wakefield postulated a link between the measles virus in the MMR vaccine and autism. This report received significant media attention worldwide, and many parents began to doubt the safety of the MMR vaccine. However, since then, The Lancet has retracted the report because it contained serious scientific flaws; many subsequent, large studies have failed to show any link between the vaccine and autism.

Gerbner and Offit 1 reviewed epidemiologic and biologic studies concerning this issue and found no evidence to support an association between use of vaccines and risk of autism. The US Institute of Medicine Immunization Safety Review Committee 2 reviewed epidemiologic studies (published and unpublished) to determine whether the measles-mumps-rubella vaccine and vaccines containing thimerosal cause autism and to identify possible biologic mechanisms for such an effect; based on the evidence, this group rejected a causal relationship between these vaccines and autism.

At this time, virtually every vaccine given to children is thimerosal-free. Small amounts of thimerosal continue to be used in multidose vials of influenza vaccine and in several other vaccines intended for use in adults (for information about vaccines that contain low levels of mercury or thimerosal, see the FDA's web site [ FDA's web site ] and Thimerosal Content in Some US Licensed Vaccines ). Thimerosal is also used in many vaccines produced in developing countries.

As with any treatment, clinicians should talk to their patients about the relative risks and benefits of recommended vaccines. In particular, clinicians must make sure that the parents of their patients are aware of the possible serious effects (including death) of vaccine-preventable childhood diseases such as measles, Hib infection, and pertussis, and clinicians discuss any concerns parents may have about vaccinating their children; resources for these discussions are available at CDC web site: Provider Resources for Vaccine Conversations with Parents (see also Talking with Parents about Vaccines for Infants and Some Common Misconceptions About Vaccination and How to Respond to Them ).

  • 1 Gerber JS, Offit PA : Vaccines and autism: A tale of shifting hypotheses, Clin Infect Dis 48(4):456-61, 2009.

  • 2 Institute of Medicine : Immunization safety review: Vaccines and autism. Washington DC, National Academies Press, 2004. Available at http://www.ncbi.nlm.nih.gov/books/NBK25349/.

Immunization for Travelers

Immunizations may be required for travel to areas where infectious diseases are endemic (see Table: Vaccines for International Travel* ,† ,‡). The CDC can provide this information; a telephone service (1-800-232-4636 [CDC-INFO]) and web site ( wwwnc.cdc.gov/travel/ ) are available 24 h/day.

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