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Immunization Practices
Immunization is one of the most beneficial and cost-effective disease-prevention measures available. As a result of effective and safe vaccines, smallpox has been eradicated, polio is close to worldwide eradication, and measles and rubella are no longer endemic in the United States. However, cases of vaccine-preventable diseases, including measles, mumps, and pertussis, continue to occur in the United States. Incidence of most vaccine-preventable diseases of childhood has been reduced by ≥99% from representative 20th century annual morbidity, usually before development of the corresponding vaccines ( Table 197.1a ), with most of the newer vaccines not achieving quite the same percentage decrease ( Table 197.1b ). An analysis of effective prevention measures recommended for widespread use by the U.S. Preventive Services Task Force (USPSTF) reported that childhood immunization received a perfect score based on clinically preventable disease burden and cost-effectiveness.
Table 197.1a
Comparison of 20th Century Annual Morbidity and Current Morbidity: Vaccine-Preventable Diseases
| DISEASE | 20TH CENTURY ANNUAL MORBIDITY * | 2016 REPORTED CASES † | PERCENT DECREASE |
|---|---|---|---|
| Smallpox | 29,005 | 0 | 100% |
| Diphtheria | 21,053 | 0 | 100% |
| Measles | 530,217 | 122 | >99% |
| Mumps | 162,344 | 5,629 | 96% |
| Pertussis | 200,752 | 15,808 | 92% |
| Polio (paralytic) | 16,316 | 0 | 100% |
| Rubella | 47,745 | 9 | >99% |
| Congenital rubella syndrome | 152 | 2 | 99% |
| Tetanus | 580 | 31 | 95% |
| Haemophilus influenzae type b (Hib) | 20,000 | 22 ‡ | >99% |
* Data from Roush SW, Murphy TV, Vaccine-Preventable Disease Table Working Group: Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States, JAMA 298(18):2155–2163, 2007.
† Data from Centers for Disease Control and Prevention: Notifiable diseases and mortality tables, MMWR 66(52):ND-924–ND-941, 2018.
‡ Hib <5 yr of age. An additional 237 cases of Haemophilus influenzae (<5 yr of age) have been reported with unknown serotype.
Table 197.1b
Comparison of Pre–Vaccine Era Estimated Annual Morbidity With Current Estimate: Vaccine-Preventable Diseases
| DISEASE | PRE–VACCINE ERA ANNUAL ESTIMATE * | 2016 ESTIMATE (UNLESS OTHERWISE SPECIFIED) | PERCENT DECREASE |
|---|---|---|---|
| Hepatitis A | 117,333 * | 4,000 † | 97% |
| Hepatitis B (acute) | 66,232 * | 20,900 † | 68% |
| Pneumococcus (invasive) | |||
| All ages | 63,067 * | 30,400 § | 52% |
| <5 yr of age | 16,069 * | 1,700 § | 89% |
| Rotavirus (hospitalizations, <3 yr of age) | 62,500 ‡ | 30,625 ‖ | 51% |
| Varicella | 4,085,120 * | 102,128 ¶ | 98% |
* Data from Roush SW, Murphy TV; Vaccine-Preventable Disease Table Working Group: Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States, JAMA 298(18):2155–2163, 2007.
† Data from Centers for Disease Control and Prevention: Viral hepatitis surveillance—United States, 2016.
‡ Data from Centers for Disease Control and Prevention: Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices, MMWR Recomm Rep 58(RR-2):1–25, 2009.
§ Data from Centers for Disease Controls and Prevention: Active bacterial core surveillance, 2016 (unpublished).
‖ Data from New Vaccine Surveillance Network 2017 data: U.S. rotavirus disease now has biennial pattern (unpublished).
¶ Data from Centers for Disease Control and Prevention: Varicella Program, 2017 (unpublished).
Immunization is the process of inducing immunity against a specific disease. Immunity can be induced either passively or actively . Passive immunity is generated through administration of an antibody-containing preparation. Active immunity is achieved by administering a vaccine or toxoid to stimulate the immune system to produce a prolonged humoral and/or cellular immune response. As of 2019, infants, children, and adolescents in the United States are recommended to be routinely immunized against 16 pathogens : Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertusis, polio virus, Haemophilus influenzae type b ( Hib ), hepatitis A, hepatitis B, measles virus, mumps virus, rubella virus, rotavirus, varicella zoster virus, pneumococcus, meningococcus, influenza virus, and human papillomavirus ( HPV ).
Passive Immunity
Rather than producing antibodies through the body's own immune system, passive immunity is achieved by administration of preformed antibodies. Protection is immediate, yet transient, lasting weeks to months. Products used include:
- ◆
Immunoglobulin administered intramuscularly ( IGIM ), intravenously ( IGIV ), or subcutaneously ( IGSC )
- ◆
Specific or hyperimmune immunoglobulin preparations administered IM or IV
- ◆
Antibodies of animal origin
- ◆
Monoclonal antibodies
Passive immunity also can be induced naturally through transplacental transfer of maternal antibodies (IgG) during gestation. This transfer can provide protection during an infant's 1st few mo of life; other antibodies (IgA) are transferred to the infant during breastfeeding. Protection for some diseases can persist for as long as 1 yr after birth, depending on the quantity of antibody transferred and the time until levels fall below those considered protective.
The major indications for inducing passive immunity are immunodeficiencies in children with B-lymphocyte defects who have difficulty making antibodies (e.g., hypogammaglobulinemia, secondary immunodeficiencies), who have exposure to infectious diseases or to imminent risk of exposure when there is inadequate time for them to develop an active immune response to a vaccine (e.g., newborn exposed to maternal hepatitis B), and who have infectious diseases that require antibody administration as part of the specific therapy ( Table 197.2 ).
Table 197.2
Immunoglobulin and Animal Antisera Preparations
Data from American Academy of Pediatrics: Passive immunization. In Kimberlin DW, Brady MT, Jackson MA, Long SS, editors: Red Book 2018: Report of the Committee on Infectious Diseases, ed 31, Elk Grove Village, IL, 2018, American Academy of Pediatrics. (Recommendations for use of specific immune globulins are located in the sections for specific diseases in Section 3 of Red Book .)
| PRODUCT | MAJOR INDICATIONS |
|---|---|
| Immune globulin intramuscular (IGIM) | Replacement therapy in antibody-deficiency disorders Hepatitis A prophylaxis Measles prophylaxis Rubella prophylaxis (pregnant women) |
| Immune globulin intravenous (IGIV) | Replacement therapy in antibody-deficiency disorders Kawasaki disease Pediatric HIV infection Hypogammaglobulinemia in chronic B-lymphocyte lymphocytic leukemia Varicella postexposure prophylaxis Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy Toxic shock syndrome May be useful in a variety of other conditions |
| Immune globulin subcutaneous (IGSC) | Treatment of patients with primary immunodeficiencies |
| Hepatitis B immunoglobulin (IM) | Postexposure prophylaxis |
| Prevention of perinatal infection in infants born to hepatitis B surface antigen–positive mothers | |
| Rabies immunoglobulin (IM) | Postexposure prophylaxis |
| Tetanus immunoglobulin (IM) | Wound prophylaxis |
| Treatment of tetanus | |
| Varicella-zoster immunoglobulin (VariZIG, IM) | Postexposure prophylaxis of susceptible people at high risk for complications from varicella |
| Cytomegalovirus (IV) | Prophylaxis of disease in seronegative transplant recipients |
| Vaccinia immunoglobulin (IV) | Reserved for certain complications of smallpox immunization and has no role in treatment of smallpox |
| Human botulism (IV), BabyBIG | Treatment of infant botulism |
| Diphtheria antitoxin, equine | Treatment of diphtheria |
| Heptavalent botulinum antitoxin against all 7 (A-G) botulinum toxin types (BAT) | Treatment of noninfant food and wound botulism |
| Palivizumab (monoclonal antibody), humanized mouse (IM) | Prophylaxis for infants against respiratory syncytial virus (see Chapter 287 ) |
Intramuscular Immunoglobulin
Immunoglobulin is a sterile antibody-containing solution, usually derived through cold ethanol fractionation of large pools of human plasma from adults. Antibody concentrations reflect the infectious disease exposure and immunization experience of plasma donors. Intramuscular immunoglobulin (IGIM) contains 15–18% protein and is predominantly IgG. Intravenous use of human IGIM is contraindicated. Immunoglobulin is not known to transmit infectious agents, including viral hepatitis and HIV. The major indications for immunoglobulin are:
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Replacement therapy for children with antibody deficiency disorders
- ◆
Measles prophylaxis
- ◆
Hepatitis A prophylaxis
For replacement therapy , the usual dose of IGIM is 100 mg/kg (equivalent to 0.66 mL/kg) monthly. The usual interval between doses is 2-4 wk depending on trough IgG serum concentrations and clinical response. In practice, IGIV has replaced IGIM for replacement therapy.
IGIM can be used to prevent or modify measles if administered to susceptible children within 6 days of exposure (usual dose: 0.5 mL/kg body weight; maximum dose: 15 mL). The recommended dose of IGIV is 400 mL/kg. Data suggest that measles vaccine, if given within 72 hr of measles exposure, will provide protection in some cases. Measles vaccine and immunoglobulin should not be administered at the same time.
Two methods are available for postexposure prophylaxis against hepatitis A depending on the patient's age: hepatitis A immunization or immunoglobulin. In those 12 mo-40 yr of age, hepatitis A immunization is preferred over immunoglobulin for postexposure prophylaxis and for protection of people traveling to areas where hepatitis A is endemic. Children 6-11 mo old should receive a dose of hepatitis A vaccine before international travel. However, the dose of hepatitis A vaccine received before 12 mo should not be counted in determining compliance with the recommended 2-dose schedule. In adults >40 yr, immunoglobulin may be administered for prophylaxis and for postexposure prophylaxis to people traveling internationally to hepatitis A–endemic areas (0.06 mL/kg). Immunoglobulin is preferred over hepatitis A immunization if there is an underlying immunodeficiency or chronic liver disease.
The most common adverse reactions to immunoglobulin are pain and discomfort at the injection site and, less commonly, flushing, headache, chills, and nausea. Serious adverse events are rare and include chest pain, dyspnea, anaphylaxis, and systemic collapse. Immunoglobulin should not be administered to people with selective IgA deficiency, who can produce antibodies against the trace amounts of IgA in immunoglobulin preparations and can develop reactions after repeat doses. These reactions can include fever, chills, and a shock-like syndrome. Because these reactions are rare, testing for selective IgA deficiencies is not recommended.
Intravenous Immunoglobulin
IGIV is a highly purified preparation of immunoglobulin antibodies prepared from adult plasma donors using alcohol fractionation and is modified to allow intravenous (IV) use. IGIV is more than 95% IgG and is tested to ensure minimum antibody titers to Corynebacterium diphtheriae , hepatitis B virus, measles virus, and poliovirus. Antibody concentrations against other pathogens vary widely among products and even among lots from the same manufacturer. Liquid and lyophilized powder preparations are available. IGIV does not contain thimerosal.
Not all IGIV products are approved by the U.S. Food and Drug Administration (FDA) for all indications. The major recommended FDA-approved indications for IGIV are:
- ◆
Replacement therapy for primary immunodeficiency disorders
- ◆
Kawasaki disease to prevent coronary artery abnormalities and shorten the clinical course
- ◆
Replacement therapy for prevention of serious bacterial infections in children infected with HIV
- ◆
Prevention of serious bacterial infections in people with hypogammaglobulinemia in chronic B-lymphocyte leukemia
- ◆
Immune-mediated thrombocytopenia to increase platelet count
IGIV may be helpful for patients with severe toxic shock syndrome, Guillain-Barré syndrome, and anemia caused by parvovirus B19. IGIV is also used for many other conditions based on clinical experience. IGIV may be used for varicella after exposure when varicella-zoster immune globulin is not available.
Reactions to IGIV may occur in up to 25% of patients. Some of these reactions appear to be related to the rate of infusion and can be mitigated by decreasing the rate. Such reactions include fever, headache, myalgia, chills, nausea, and vomiting. More serious reactions, including anaphylactoid events, thromboembolic disorders, aseptic meningitis, and renal insufficiency, have rarely been reported. Renal failure occurs mainly in patients with preexisting renal dysfunction.
Specific or hyperimmune immunoglobulin preparations are derived from donors with high titers of antibodies to specific agents and are designed to provide protection against those agents (see Table 197.2 ).
Subcutaneous Immunoglobulin
Subcutaneous administration of immunoglobulin (IGSC) is safe and effective in children and adults with primary immune deficiency disorders. Smaller doses administered weekly result in less fluctuation of serum IgG concentrations over time. Systemic reactions are less frequent than with IGIV, and the most common adverse effects of IGSC are injection-site reactions. There are no data on administration of IGIM by the subcutaneous route.
Hyperimmune Animal Antisera Preparations
Animal antisera preparations are derived from horses. The immunoglobulin fraction is concentrated using ammonium sulfate, and some products are further treated with enzymes to decrease reactions to foreign proteins. The following 2 equine antisera preparations are available for humans (as of 2018):
- ◆
Diphtheria antitoxin , which can be obtained from the U.S. Centers for Disease Control and Prevention ( http://www.cdc.gov/diphtheria/dat.html ) and is used to treat diphtheria.
- ◆
Heptavalent botulinum antitoxin , available from the CDC for use in adults with botulism. To request it, one can call the CDC's 24 hr line at 770-488-7100. This product contains antitoxin against all 7 (A-G) botulinum toxin types.
Great care must be exercised before administering animal-derived antisera because of the potential for severe allergic reactions. Due caution includes testing for sensitivity before administration, desensitization if necessary, and treating potential reactions, including febrile events, serum sickness, and anaphylaxis. For infant botulism, IVIG (BabyBIG), a human-derived antitoxin, is licensed and should be used.
Monoclonal Antibodies
Monoclonal antibodies (mAbs) are antibody preparations produced against a single antigen. They are mass-produced from a hybridoma, a hybrid cell used as the basis for production of large amounts of antibodies. A hybridoma is created by fusing an antibody-producing B lymphocyte with a fast-growing immortal cell such as a cancer cell. Palivizumab is used for prevention of severe disease from respiratory syncytial virus (RSV) among children ≤24 mo old with bronchopulmonary dysplasia (BPD, a form of chronic lung disease), a history of premature birth, or congenital heart lesions or neuromuscular diseases. The American Academy of Pediatrics (AAP) has developed specific recommendations for use of palivizumab (see Chapter 287 ). Monoclonal antibodies also are used to prevent transplant rejection and to treat some types of cancer, autoimmune diseases, and asthma. Use of mAbs against interleukin (IL)-2 and tumor necrosis factor (TNF)-α are being used as part of the therapeutic approach to patients with a variety of malignant and autoimmune diseases.
Serious adverse events associated with palivizumab are rare, primarily including cases of anaphylaxis and hypersensitivity reactions. Adverse reactions to mAbs directed at modifying the immune response, such as antibodies against IL-2 or TNF-α, can be more serious and include cytokine release syndrome, fever, chills, tremors, chest pain, immunosuppression, and infection with various organisms, including mycobacteria.
Active Immunization
Vaccines are defined as whole or parts of microorganisms administered to prevent an infectious disease. Vaccines can consist of whole inactivated microorganisms (e.g., polio, hepatitis A), parts of the organism (e.g., acellular pertussis, HPV, hepatitis B), polysaccharide capsules (e.g., pneumococcal and meningococcal polysaccharide vaccines), polysaccharide capsules conjugated to protein carriers (e.g., Hib, pneumococcal, and meningococcal conjugate vaccines), live-attenuated microorganisms (e.g., measles, mumps, rubella, varicella, rotavirus, and live-attenuated influenza vaccines), and toxoids (e.g., tetanus, diphtheria) ( Table 197.3 ). A toxoid is a bacterial toxin modified to be nontoxic but still capable of inducing an active immune response against the toxin.
Table 197.3
Currently Available * Vaccines in the United States by Type
Data from US Food and Drug Administration: Vaccines licensed for use in the United States. http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm093833.htm .
| PRODUCT | TYPE |
|---|---|
| Adenovirus | Live, oral vaccine indicated for active immunization for the prevention of febrile acute respiratory disease caused by adenovirus types 4 and 7, for use in military populations 17-50 yr of age |
| Anthrax vaccine adsorbed | Cell-free filtrate of components including protective antigen |
| Bacille Calmette-Guérin (BCG) vaccine | Live-attenuated mycobacterial strain used to prevent tuberculosis in very limited circumstances |
| Cholera vaccine | Oral vaccine containing live-attenuated Vibrio cholerae CVD 103-HgR strain for protection against serogroup O1 in adults age 18-64 traveling to cholera-affected areas |
| Diphtheria and tetanus toxoids adsorbed | Toxoids of diphtheria and tetanus |
| Diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine | Toxoids of diphtheria and tetanus and purified and detoxified components from Bordetella pertussis |
| DTaP–hepatitis B–inactivated polio vaccine (DTaP-HepB-IPV) | DTaP with hepatitis B surface antigen (HBsAg) produced through recombinant techniques in yeast with inactivated whole polioviruses |
| DTaP with IPV and Haemophilus influenzae type b (Hib) (DTaP-IPV/Hib) | DTaP with inactivated whole polioviruses and Hib polysaccharide conjugated to tetanus toxoid |
| DTaP and inactivated polio vaccine (DTaP-IPV) | DTaP with inactivated whole polioviruses |
| Hib conjugate vaccine (Hib) | Polysaccharide conjugated to either tetanus toxoid or meningococcal group B outer membrane protein |
| Hepatitis A vaccine (HepA) | Inactivated whole virus |
| Hepatitis A–hepatitis B vaccine (HepA-HepB) | Combined hepatitis A and B vaccine |
| Hepatitis B vaccine (HepB) | HBsAg produced through recombinant techniques in yeast |
| Human papillomavirus vaccine 9-valent (9vHPV) | The L1 capsid proteins of HPV types 6 and 11 to prevent genital warts and types 16 18, 31, 33, 45, 52, and 58 to prevent cervical cancer (9vHPV). |
| Influenza virus vaccine inactivated (IIV † ) | Available either as trivalent (A/H 3 N 2 , A/H 1 N 1 , and B) split and purified inactivated vaccines containing the hemagglutinin (H) and neuraminidase (N) of each type or as quadrivalent preparations (which include representative strains from 2 B strains in addition to the 2 influenza A strains in trivalent inactivated influenza vaccine) |
| Influenza virus vaccine live-attenuated, intranasal (LAIV) | Live-attenuated, temperature-sensitive, cold-adapted quadrivalent vaccine containing the H and N genes from the wild strains reassorted to have the 6 other genes from the cold-adapted parent |
| Japanese encephalitis vaccine | Purified, inactivated whole virus |
| Measles, mumps, rubella (MMR) vaccine | Live-attenuated viruses |
| Measles, mumps, rubella, varicella (MMRV) vaccine | Live-attenuated viruses |
| Meningococcal conjugate vaccine against serogroups A, C, W135, and Y (MCV4) | Polysaccharide from each serogroup conjugated to diphtheria toxoid CRM 197 protein |
| Meningococcal polysaccharide vaccine against serogroups A, C, W135, and Y (MPSV4) | Polysaccharides from each of the serogroups conjugated to diphtheria toxoid protein |
| Meningococcal B (MenB) | Recombinant proteins from serogroup B developed in Escherichia coli |
| Pneumococcal conjugate vaccine (13 valent) (PCV13) | Pneumococcal polysaccharides conjugated to diphtheria toxin CRM 197 , contains 13 serotypes that accounted for >80% of invasive disease in young children prior to vaccine licensure |
| Pneumococcal polysaccharide vaccine (23 valent) (PPSV23) | Pneumococcal polysaccharides of 23 serotypes responsible for 85–90% of bacteremic disease in the United States |
| Poliomyelitis (inactivated, enhanced potency) (IPV) | Inactivated whole virus highly purified from monkey kidney cells, trivalent types 1, 2, and 3 |
| Rabies vaccines (human diploid and purified chicken fibroblasts) | Inactivated whole virus |
| Rotavirus vaccines (RV5 and RV1) | Bovine rotavirus pentavalent vaccine (RV5) live reassortment attenuated virus, and human live-attenuated virus (RV1) |
| Smallpox vaccine | Vaccinia virus, an attenuated poxvirus that provides cross-protection against smallpox (variola) |
| Tetanus and diphtheria toxoids, adsorbed (Td, adult use) | Tetanus toxoid plus a reduced quantity of diphtheria toxoid compared to diphtheria toxoid used for children <7 yr of age |
| Tetanus and diphtheria toxoids adsorbed plus acellular pertussis (Tdap) vaccine | Tetanus toxoid plus a reduced quantity of diphtheria toxoid plus acellular pertussis vaccine to be used in adolescents and adults and in children 7 through 10 yr of age who have not been appropriately immunized with DTaP |
| Typhoid vaccine (polysaccharide) | Vi capsular polysaccharide of Salmonella typhi Ty2 strain |
| Typhoid vaccine (oral) | Live-attenuated Ty21a strain of S. typhi |
| Varicella vaccine | Live-attenuated Oka/Merck strain |
| Yellow fever vaccine | Live-attenuated 17D-204 strain |
| Herpes zoster (shingles) vaccine | Live-attenuated Oka/Merck strain for use in adults ≥60 yr old (Zostavax) Recombinant zoster vaccine, adjuvanted (Shingrix) for use in adults ≥50 years |
† There are various types of inactivated flu vaccines—IIV3, IIV4, RIV4, ccIIV4, aIIV3.
Vaccines can contain a variety of other constituents besides the immunizing antigen. Suspending fluids may be sterile water or saline but can be a complex fluid containing small amounts of proteins or other constituents used to grow the immunobiologic culture. Preservatives, stabilizers, and antimicrobial agents are used to inhibit bacterial growth and prevent degradation of the antigen. Such components can include gelatin, 2-phenoxyethanol, and specific antimicrobial agents. Preservatives are added to multidose vials of vaccines, primarily to prevent bacterial contamination on repeated entry of the vial. In the past, many vaccines for children contained thimerosal , a preservative containing ethyl mercury. Removal of thimerosal as a preservative from vaccines for children began as a precautionary measure in 1999 in the absence of any data on harm from the preservative. This objective was accomplished by switching to single-dose packaging. Of the vaccines recommended for young children, only some preparations of influenza vaccine contain thimerosal as a preservative. *
* The thimerosal content in U.S.-licensed vaccines currently being manufactured is listed at http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/ucm096228.htm#pres .
Adjuvants are used in some vaccines to enhance the immune response. In the United States, the only adjuvants currently licensed by the FDA to be part of vaccines are aluminum salts ; AsO 4 , composed of 3-O-desacyl-4′-monophosphoryl 301 lipid A (MPL) adsorbed on to aluminum (as hydroxide salt); and MF59 and 1018 adjuvant. AsO 4 is found in 1 type of HPV vaccine, no longer available in the United States, but used in Europe. MF59 is an oil-in-water emulsion found in 1 type of influenza vaccine approved for people ≥65 yr old. 1018 is an immunostimulatory sequence adjuvant used in HepB-CpG, a hepatitis B vaccine approved for persons > 18 yr. HepB-CpG contains yeast-derived recombinant HBsAg and is prepared by combining purified HBsAg with small synthetic immunostimulatory cytidine-phosphate-guanosine oligodeoxynucleotide motifs. The 1018 adjuvant binds to Toll-like receptor 9 to simulate a directed immune response to HBsAg. Vaccines with adjuvants should be injected deeply into muscle masses to avoid local irritation, granuloma formation, and necrosis associated with SC or intracutaneous administration.
Vaccines can induce immunity by stimulating antibody formation, cellular immunity, or both. Protection induced by most vaccines is thought to be mediated primarily by B lymphocytes, which produce antibodies. Such antibodies can inactivate toxins, neutralize viruses, and prevent their attachment to cellular receptors, facilitate phagocytosis and killing of bacteria, interact with complement to lyse bacteria, and prevent adhesion to mucosal surfaces by interacting with the bacterial cell surface.
Most B-lymphocyte responses require the assistance of CD4 helper T lymphocytes. These T-lymphocyte–dependent responses tend to induce high levels of functional antibody with high avidity. The T-dependent responses mature over time from primarily an IgM response to a persistent, long-term IgG response and induce immunologic memory that leads to enhanced responses on boosting. T-lymphocyte–dependent vaccines , which include protein moieties, induce good immune responses even in young infants. In contrast, polysaccharide antigens induce B-lymphocyte responses in the absence of T-lymphocyte help. These T-lymphocyte–independent vaccines are associated with poor immune responses in children <2 yr old and with short-term immunity and absence of an enhanced or booster response on repeat exposure to the antigen. With some polysaccharide vaccines, repeat doses actually are associated with reduced responses, as measured by antibody concentrations, compared to 1st doses (i.e., hyporesponsive ). To overcome problems with plain polysaccharide vaccines, polysaccharides have been conjugated , or covalently linked, to protein carriers, converting the vaccine to a T-lymphocyte–dependent vaccine. In contrast to plain polysaccharide vaccines, conjugate vaccines induce higher-avidity antibody, immunologic memory leading to booster responses on repeat exposure to the antigen, long-term immunity, and community protection by decreasing carriage of the organism ( Table 197.4 ). As of 2018 in the United States, licensed conjugate vaccines are available to prevent Hib, pneumococcal, and meningococcal diseases.
Table 197.4
Characteristics of Polysaccharide and Conjugate Vaccines
| CHARACTERISTIC | CONJUGATE | POLYSACCHARIDE |
|---|---|---|
| T-lymphocyte–dependent immune response | Yes | No |
| Immune memory | Yes | No |
| Persistence of protection | Yes | No |
| Booster effect | Yes | No |
| Reduction of carriage | Yes | No |
| Community protection | Yes | No |
| Lack of hyporesponsiveness | Yes | No |
Serum antibodies may be detected as soon as 7-10 days after initial injection of antigen. Early antibodies are usually of the IgM class that can fix complement. IgM antibodies tend to decline as IgG antibodies increase. The IgG antibodies tend to peak approximately 1 mo after vaccination and with most vaccines persist for some time after a primary vaccine course. Secondary or booster responses occur more rapidly and result from rapid proliferation of memory B and T lymphocytes.
Assessment of the immune response to most vaccines is performed by measuring serum antibodies. Although detection of serum antibody at levels considered protective after vaccination can indicate immunity, loss of detectable antibody over time does not necessarily mean susceptibility to disease. Some vaccines induce immunologic memory, leading to a booster or anamnestic response on exposure to the microorganism, with resultant protection from disease. In some cases, cellular immune response is used to evaluate the status of the immune system. Certain vaccines (e.g., acellular pertussis) do not have an accepted serologic correlate of protection.
Live-attenuated vaccines routinely recommended for children and adolescents include measles, mumps, and rubella ( MMR ); MMR and varicella ( MMRV ); rotavirus; and varicella. In addition, a cold-adapted, live-attenuated quadrivalent influenza vaccine ( LAIV ) is available in the past for persons 2-49 yr old who do not have conditions that place them at high risk for complications from influenza. Notably lower vaccine effectiveness during the 2013–2016 influenza seasons has resulted in LAIV not being recommended in the United States for the 2016–2017 and 2017–2018 seasons; LAIV is recommended for the 2018–1019 season. Live-attenuated vaccines tend to induce long-term immune responses. They replicate, often similarly to natural infections, until an immune response inhibits reproduction. Most live vaccines are administered in 1-dose or 2-dose schedules. The purpose of repeat doses, such as a 2nd dose of the MMR or MMRV vaccine, is to induce an initial immune response in those who failed to respond to the 1st dose. Because influenza viruses tend to mutate to evade preexisting immunity to prior strains, at least 1 of the strains in influenza vaccines each year is often different than in the previous year. Thus, influenza vaccines are recommended to be administered yearly.
The remaining vaccines in the recommended schedule for children and adolescents are inactivated vaccines. Inactivated vaccines tend to require multiple doses to induce an adequate immune response and are more likely than live-attenuated vaccines to need booster doses to maintain that immunity. However, some inactivated vaccines appear to induce long-term or perhaps lifelong immunity, after a primary series, including hepatitis B vaccine and inactivated polio vaccine.
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