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Overview of Immunization


Margot L. Savoy

, MD, MPH, Lewis Katz School of Medicine at Temple University

Last full review/revision Oct 2020| Content last modified Oct 2020
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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.

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, diphtheria) are now rare or have been eliminated. However, except for smallpox, these infections still occur in parts of the developing world.

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

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, bacille Calmette-Guérin, typhoid, yellow fever) are not routinely given but are recommended only for specific people and circumstances (see the CDC's Recommended Adult Immunization Schedule and under the specific disorder, elsewhere in THE MANUAL; 1).

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-year period. Also, vaccination rates tend to be lower in blacks, Asians, and Hispanics than in whites.


Vaccines Available in the US




Inactivated bacteria


Bacille Calmette-Guérin (BCG) (for tuberculosis)

Live Mycobacteria bovis

Intradermal or subcutaneous

Live-attenuated vaccine


Toxoids and inactivated bacterial components


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

Toxoids, recombinant viral antigen, and inactivated poliovirus


Toxoids, inactivated bacteria, and inactivated poliovirus


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


Ebola (rVSV-ZEBOV)

Live-attenuated recombinant vaccine (protects against only the Zaire ebolavirus species)


Haemophilus influenzae type b conjugate (Hib)

Bacterial polysaccharide conjugated to protein


Hib-hepatitis B (Hib-HepB)

H. influenzae type b polysaccharide conjugated to protein and recombinant hepatitis B viral antigen


Hepatitis A (HepA)

Inactivated virus


Hepatitis B (HepB)

Recombinant viral antigen


Hepatitis A and hepatitis B

Inactivated virus plus recombinant viral antigens


Hib conjugate vaccine (HbCV) plus Hep B

Bacterial polysaccharide conjugate plus inactivated viral antigen


Human papillomavirus (HPV)

Noninfectious viruslike particles


Influenza (live-attenuated influenza vaccine [LAIV])

Live influenza A and B virus


Influenza, types A and B (inactivated)

Inactivated virus or viral components

IM or intradermal

Inactivated virus


Measles-mumps-rubella (MMR)

Live viruses


Measles-mumps-rubella-varicella (MMRV)

Live viruses


Meningococcal, polysaccharide (MPSV4)

Bacterial polysaccharides of serogroups A, C, Y, and W


Meningococcal, conjugate (MenACWY)

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


Meningococcal group B (MenB)

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


Pneumococcal, polysaccharide (PPSV23)

Bacterial polysaccharides of 23 pneumococcal types

IM or subcutaneous

Pneumococcal, conjugate (PCV13)

Polysaccharides of 13 types, conjugated to diphtheria toxin


Poliovirus (IPV)

Inactivated viruses of all 3 serotypes


Inactivated virus

Intradermal* or subcutaneous

Live virus


Live vaccinia virus

Intradermal via multiple puncture device

Inactivated toxin (toxoid)


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

Inactivated toxins (toxoids)


Tuberculosis (see BCG)

Capsular polysaccharide



Live-attenuated vaccine


Live virus


Live virus


Zoster (shingles)

Recombinant, adjuvanted


Zoster (shingles)

Live virus


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

† Preparations with adjuvants should be given IM.

‡ Tetanus-diphtheria contains the same amount of tetanus toxoid as diphtheria-tetanus-pertussis or diphtheria-tetanus but a reduced dose of diphtheria toxoid.

IM = intramuscular.

Modified from the Vaccine Recommendations of the Advisory Committee for Immunization Practices (ACIP). Accessed 10/08/20.

(See also PATH's Vaccine Resource Library.)

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 intramuscularly into the midlateral thigh (in infants and toddlers) or into the deltoid muscle (in school-aged children and adults). Some vaccines are given subcutaneously. For details on vaccine administration, see the General Best Practice Guidelines for Vaccine Administration from the Advisory Committee for Immunization Practices (ACIP) and Administering Vaccines to Adults from the Immunization Action Coalition.

Shoulder injury related to vaccine administration (SIRVA) may be caused by the unintentional injection of a vaccine into tissues and structures under the deltoid muscle of the shoulder (2).

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


Needle Size


By route


23–25 gauge

5/8" long

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


23–25 gauge for injection into the deltoid

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

By sex and weight for intramuscular injection

Male or female, < 60 kg

5/8–1" long

A 5/8" needle may be used for intramuscular injection into 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 of vaccines is safe, effective, and convenient; 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 weeks.

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 weeks apart.

Vaccine administration references

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.


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, 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.

Other recommendations for patients with a history of egg allergy include the following:

  • Only hives after exposure to egg: Patients should be given an age-appropriate influenza vaccine.

  • Other reactions to eggs (eg, angioedema, respiratory distress, light-headedness, recurrent emesis, and reactions that required epinephrine or other emergency treatment): Patients may be given an age-appropriate influenza vaccine. However, the vaccine should be given in a medical setting and supervised by a health care practitioner who can recognize and manage severe allergic reactions.

NOTE: 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.


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):

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 weeks 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 weeks after a previous influenza or diphtheria-tetanus-acellular pertussis (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 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.


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 weeks], 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). Patients taking immune-suppressing drugs for any of a wide variety of disorders, including dermatologic, gastrointestinal, rheumatologic, and lung disorders, should not receive live-virus vaccines. For patients receiving long-term immunosuppressive therapy, clinicians should discuss risks and benefits of vaccination and/or revaccination with an infectious disease specialist.

Pearls & Pitfalls

  • Live-virus vaccines should not be given to immunocompromised patients, including patients receiving immunosuppressive therapy.

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/mcL (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 years).

Live-microbial 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 weeks before or 6 to 12 weeks after the immune globulins.

Live-microbial vaccines include the following:


Pregnancy is a contraindication to vaccination with MMR, intranasal (live) influenza vaccine, varicella, and other live-virus vaccines.

The Advisory Committee on Immunization Practices recommends delaying vaccination with HPV vaccine and recombinant zoster vaccine until after pregnancy. (See Recommended Adult Immunization Schedule by Medical Condition and Other Indications).


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 two surveillance systems: the CDC's and the Food and Drug Administration's (FDA) Vaccine Adverse Event Reporting System (VAERS)and the Vaccine Safety Datalink (VSD).

VAERS is a safety program cosponsored by the FDA and the CDC; VAERS collects reports from individual patients who believe that they had an adverse event after a recent vaccination. Health care practitioners are also required to report certain events after vaccination and may report events even if they are unsure the events are vaccine-related. VAERS reports originate all across the country and provide a rapid assessment of potential safety issues. However, VAERS reports can show only temporal associations between vaccination and the suspected adverse event; they do not prove causation. Thus, VAERS reports must be further evaluated using other methods. One such method uses the VSD, which uses data from 9 large managed care organizations (MCOs) representing more than 9 million people. The data include vaccine administration (noted in the medical record as part of routine care), as well as subsequent medical history, including adverse events. Unlike VAERS, the VSD includes data from patients who have not received a given vaccine as well as those who have. As a result, the VSD can help distinguish actual adverse events from symptoms and disorders that occurred coincidentally after vaccination and thus determine the actual incidence of adverse events.

Nonetheless, many parents remain concerned about the safety of childhood vaccines and their possible adverse effects (particularly autism). 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 Anti-Vaccination Movement : Measles-mumps-rubella (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.

Gerber and Offit reviewed epidemiologic and biologic studies concerning this issue and found no evidence to support an association between use of vaccines and risk of autism (1). The US Institute of Medicine Immunization Safety Review Committee 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 (2).

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 thimerosal, see the Food and Drug Administration's web site (Thimerosal and Vaccines) and the Institute for Vaccine Safety's web site for 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 (3). 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 should discuss any concerns parents may have about vaccinating their children. Resources for these discussions include the CDC's Talking with Parents about Vaccines for Infants and Parents' Guide to Childhood Immunizations.

Vaccine safety references

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 (Travelers' Health) are available 24 hours/day.

More Information about Immunization

The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

See the following Centers for Disease Control and Prevention (CDC) sites for comprehensive information about immunization schedules, recommendations for vaccine administration, vaccine resources for travelers, vaccine safety, and vaccine-related patient-friendly resources:

Drugs Mentioned In This Article

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Gammagard S/D
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