Vaccines, toxoids and other immunologics

Vaccines are substances administered to generate a protective immune response. They can be live attenuated or killed.

Toxoids are inactivated bacterial toxins. They retain the ability to stimulate the formation of antitoxins, which are antibodies directed against the bacterial toxin.

In general, killed vaccines can be administered simultaneously at separate sites. Killed and live-attenuated vaccines may be administered simultaneously at separate sites

Adjuvants are inert substances, such as aluminum salts (ie, alum), which enhance vaccine antigenicity by prolonging antigen absorption.

Immune sera are sterile solutions containing antibody derived from human (immunoglobulin [Ig]) or equine (antitoxin) sources.

Vaccines and Toxoid recommendations

In general, killed vaccines can be administered simultaneously at separate sites. Killed and live-attenuated vaccines may be administered simultaneously at separate sites. If they cannot be administered simultaneously, they can be administered at any interval between doses with the exception of cholera (killed) and yellow fever (live) vaccines, which should be given at least 3 weeks apart. If live vaccines are not administered simultaneously, their administration should be separated by at least 4 weeks.

Administration of live vaccines, such as rubella or varicella, are deferred until postpartum and are routinely recommended for new mothers who do not have evidence of immunity prior to hospital discharge. These live vaccines can be administered without regard to administration of Rho(D) Ig (RDIg) in the postpartum period. Additionally, Tdap is recommended for all new mothers who have not received a Tdap before because household contacts are frequently implicated as the source of pertussis infection in a young infant.

In general, severely immunocompromised individuals should not receive live vaccines. Patients with chronic conditions that cause limited immunodeficiency (eg, renal disease, diabetes, liver disease, and asplenia) and who are not receiving immunosuppressants may receive live-attenuated and killed vaccines, as well as toxoids.

Patients with active malignant disease may receive killed vaccines or toxoids but should not be given live vaccines. Live virus vaccines may be administered to persons with leukemia who have not received chemotherapy for at least 3 months.

If a person has been receiving high-dose corticosteroids or has had a course lasting longer than 2 weeks, then at least 1 month should pass before immunization with live virus vaccines. Responses to live and killed vaccines generally are suboptimal for human immunodeficiency virus (HIV)–infected patients and decrease as the disease progresses.

General contraindications to vaccine administration include a history of anaphylactic reaction to a previous dose or an unexplained encephalopathy occurring within 7 days of a dose of pertussis vaccine. Immunosuppression and pregnancy are temporary contraindications to live vaccines. Whenever possible, transplant patients should be immunized before transplantation. Live vaccines generally are not given after transplantation.

Diphtheria toxoid Adsorbed and Diphtheria antitoxin

Two strengths of diphtheria toxoid are available: pediatric (D) and adult, which contains less antigen. Primary immunization with D is indicated for children older than 6 weeks. Generally, D is given along with tetanus and a cellular pertussis (DTaP) vaccines at 2, 4, and 6 months of age, and then at 15 to 18 months and 4 to 6 years of age.

For non-immunized adults, a complete three-dose series of diphtheria toxoid should be administered, with the first two doses given at least 4 weeks apart and the third dose 6 to 12 months after the second. One dose in the series should be Tdap. The combined preparation, tetanus–diphtheria (Td), is recommended in adults because it contains less diphtheria toxoid than DTaP, with fewer reactions seen from the diphtheria preparation. Booster doses are given every 10 years. Adverse effects to diphtheria toxoid include mild to moderate tenderness, erythema, and induration at the injection site.

Tetanus toxoid, Tetanus toxoid Adsorbed and Tetanus Immunoglobulin

In children, primary immunization against tetanus is usually done in conjunction with diphtheria and pertussis vaccination using DTaP or a combination vaccine that includes other antigens. A 0.5-mL dose is recommended at 2, 4, 6, and 15 to 18 months of age, but the first dose can be administered as early as age 6 weeks.

In children 7 years and older and in adults who have not been previously immunized, a series of three 0.5 mL doses of Td are administered intramuscularly (IM) initially. The first two doses are given 1 to 2 months apart and the third dose 6 to 12 months later. Boosters are recommended every 10 years.

Tetanus toxoid may be given to immunosuppressed patients if indicated.

Tetanus Ig (TIg) is used to provide passive tetanus immunization after the occurrence of traumatic wounds in nonimmunized or suboptimally immunized persons. A dose of 250 to 500 units is administered IM. When administered with tetanus toxoid, separate sites for administration should be used. TIg also used for the treatment of tetanus. In this setting, a single dose of 3000 to 6000 units is administered IM.

Haemophilus Influenzae type B vaccines

Haemophilus influenzae type b (Hib) vaccines currently in use are conjugate products, consisting of either a polysaccharide or oligosaccharide of polyribosylribitol phosphate (PRP) covalently linked to a protein carrier. Hib conjugate vaccines are indicated for routine use in all infants and children younger than 5 years.

The primary series of Hib vaccination consists of 0.5-mL IM doses at 2, 4, and 6 months of age. If PRP-OMP (PRP conjugated to an outer membrane protein) is used, it should be given at ages 2 and 4 months. A booster dose is recommended at age 12 to 15 months.

For infants 7 to 11 months of age who have not been vaccinated, three doses of Hib vaccine should be given: two doses spaced 4 weeks apart and then a booster dose at age 12 to 15 months (but at least 8 weeks since the second dose). For unvaccinated children ages 12 to 14 months, two doses should be given, with an interval of 2 months between doses. In a child older than 15 months, a single dose of any of the four conjugate vaccines is indicated.

Human Papilloma virus vaccine

Bivalent (Cervarix) and quadrivalent (Gardisil) vaccines are available. Both vaccines are recommended as a three-dose series (0, 2, and 6 months) for all female patients 11 to 12 years old and ages 13 to 26 years. The quadrivalent vaccine is licensed for prevention of genital warts in female patients 9 to 26 years of age. The vaccine is well tolerated, with injection site reactions and headache and fatigue occurring as commonly as in placebo groups.

Influenza virus vaccine

Measles vaccine is a live-attenuated vaccine that is administered for primary immunization to persons 12 to 15 months of age or older, usually as a combination of measles, mumps, and rubella (MMR). A second dose is recommended at 4 to 6 years of age. The vaccine should not be given to immunosuppressed patients (except those infected with HIV) or pregnant women. HIV-infected persons who have never had measles or have never been vaccinated should be given measles-containing vaccine unless there is evidence of severe immunosuppression.

The vaccine should not be given within 1 month of any other live vaccine unless the vaccine is given on the same day (as with the MMR vaccine). Measles vaccine is indicated in all persons born after 1956 or in those who lack documentation of wild virus infection by either history or antibody titers.

Meningococcal Polysaccharide vaccine

There are two meningococcal conjugate vaccines: Menactra is licensed for individuals 9 months to 55 years old and Menveo for those 12 to 55 years old. They are recommended for all children 11 to 12 years old with a second dose at 16 years of age. The vaccine is indicated in high-risk populations such as those exposed to the disease, those in the midst of uncontrolled outbreaks, travelers to an area with epidemic hyperendemic meningococcal disease, and individuals who have terminal complement deficiencies or asplenia. Re-immunization at 5-year intervals is recommended for individuals who are at high risk. The polysaccharide vaccine should be reserved for those older than 55 years who require immunization.

Mumps vaccine

The vaccine (usually given in conjunction with measles and rubella, MMR) is given beginning at age 12 to 15 months, with a second dose prior to entry into elementary school. Two doses of mumps vaccine are recommended for school-age children, international travelers, college students, and healthcare workers born after 1956.

Post-exposure vaccination is of no benefit. Mumps vaccine should not be given to pregnant women or immunosuppressed patients. The vaccine should not be given within 6 weeks (preferably 3 months) of administration of Ig.

Pertusis vaccine

Acellular pertussis vaccine is usually administered in combination with diphtheria and tetanus toxoids (as DTaP). The primary immunization series for pertussis vaccine consists of four doses given at ages 2, 4, 6, and 15 to 18 months. A booster dose is recommended at age 4 to 6 years. Pertussis vaccine is administered in combination with diphtheria and tetanus (DTaP). Administration of an acellular pertussis-containing vaccine is also recommended for adolescents once between ages 11 and 18 years. In addition, adolescents should receive a pertussis-containing vaccine with their next dose of Td toxoids.

Systemic reactions, such as moderate fever, occur in 3% to 5% of those receiving vaccines. Very rarely, high fever, febrile seizures, persistent crying spells, and hypotonic hyporesponsive episodes occur after vaccination.

There are only two contraindications to pertussis administration: (1) an immediate anaphylactic reaction to a previous dose and (2) encephalopathy within 7 days of a previous dose, with no evidence of other cause.

Pneumococcal vaccines

Pneumococcal polysaccharide vaccine is a mixture of capsular polysaccharides from 23 of the 83 most prevalent types of Streptococcus pneumoniae seen in the United States. Pneumococcal vaccine is recommended for the following immunocompetent persons:

Persons 65 years or older. If an individual received vaccine more than 5 years earlier and was younger than 65 at the time of administration, revaccination should be given.

Persons ages 2 to 64 years with chronic illness

Persons ages 2 to 64 years with functional or anatomical asplenia. When splenectomy is planned, pneumococcal vaccine should be given at least 2 weeks before surgery.

Persons ages 2 to 64 years living in environments where the risk of invasive pneumococcal disease or its complications is increased. This does not include daycare center employees and children.

Because children younger than 2 years do not respond adequately to the pneumococcal polysaccharide vaccine, a heptavalent pneumococcal conjugate vaccine (PCV) was created that can be administered at 2, 4, and 6 months of age and between 12 and 15 months of age.

PCV 13 valent, (PCV13) is administered as a 0.5-mL IM injection at 2, 4, and 6 months of age and between 12 and 15 months of age. A single dose of PCV13 should be administered to children aged 6 to 18 years with sickle cell disease or splenic dysfunction, HIV infection, immunocompromising conditions, cochlear implant, or cerebral spinal fluid leak should be immunized. It is also licensed for individuals aged 50 years and older.

Varicella virus vaccine

Varicella virus vaccine is recommended for all children 12 to 18 months of age, with a second dose prior to entering school between 4 and 6 years of age. It is also recommended for persons above this age if they have not had chickenpox. Persons ages 13 years and older should receive two doses separated by 4 to 8 weeks. The vaccine is contraindicated in immunosuppressed or pregnant patients. Children with asymptomatic or mildly symptomatic HIV should receive two doses of varicella vaccine 3 months apart.

Varicella zoster vaccine

The zoster vaccine is recommended for immunocompetent individuals older than 60 years. It should not be used in immunocompromised individuals, including those with HIV or malignancies or in pregnant women. Administration of varicella zoster Ig is by the IM route (never IV).

Rho(D) Ig (RDIg)

Rho(D) Ig (RDIg) suppresses the antibody response and formation of anti-Rho(D) in Rho(D)- negative, Du-negative women exposed to Rho(D)-positive blood and prevents the future chance of erythroblastosis fetalis in subsequent pregnancies with a Rho(D)-positive fetus.

RDIg, when administered IM within 72 hours of delivery of a full-term infant, reduces active antibody formation from 12% to between 1% and 2%. RDIg is also used in the case of a premenopausal woman who is Rho(D) negative and has inadvertently received Rho(D)-positive blood or blood products.  RDIg may be used after abortion, miscarriage, amniocentesis, or abdominal trauma.


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