Principles of Vaccination Inactivated Vaccines Inactivated Vaccines Inactivated vaccines are produced by growing the bacterium heat Cannot replicate e cas “heoatrneteceeulating e components to be included in the vaccine (e.g.,the polysac charide capsule of pneumococcus). .Antibody titer diminishes with time and tire dose of a ed ot These vaccines cannot cause disease from infection,even in an immunodeficient person Inactivated antigens are less by circulating anti y than are liv in the blood (in infa antibody-containing blood products). ivated ultiple doses.I he fir n general, Inactivated Vaccines se rwhee-colvaceiner develops after the second or third dose.In contrast to live b8ga8s vaccines,in which the immune response closely resemble esponse t ctivat ·Bacterial eatob8gg resulrs.inactivated antigens diminish with time.As a result,some inactivated vaccines may Currently available whole-cell inactivated vaccines are Inactivated Vaccines mired whole viral vaccines(polio,rabies. vated hole virus influenza vaccin Fionalvaccines States.Fractional vaccines include subunits (he influenza,acellular pertussis)and toxoids(diphtheria, Toxoid diphtheria,tetanus le in the UAe available in the future. Polysaccharide Vaccines bunit vaccin ain sugar mo Polysaccharide Vaccines ce caps Pure in mencal dieae,and naride vaccine for ug. 。 ningococcal 6
1 Inactivated Vaccines Inactivated vaccines are produced by growing the bacterium or virus in culture media, then inactivating it with heat and/or chemicals (usually formalin). In the case of fractional vaccines, the organism is further treated to purify only those components to be included in the vaccine (e.g., the polysaccharide capsule of pneumococcus). Inactivated vaccines are not alive and cannot replicate. The entire dose of antigen is administered in the injection. These vaccines cannot cause disease from infection, even in an immunodeficient person. Inactivated antigens are less affected by circulating antibody than are live agents. Inactivated vaccines may be given when antibody is present in the blood (e.g., in infancy or following receipt of antibody-containing blood products). Inactivated vaccines always require multiple doses. In general, the first dose does not produce protective immunity, but “primes” the immune system. A protective immune response develops after the second or third dose. In contrast to live vaccines, in which the immune response closely resembles natural infection, the immune response to an inactivated vaccine is mostly humoral. Little or no cellular immunity results. Antibody titers against inactivated antigens diminish with time. As a result, some inactivated vaccines may require periodic supplemental doses to increase, or “boost,” antibody titers. Currently available whole-cell inactivated vaccines are limited to inactivated whole viral vaccines (polio, rabies, and hepatitis A). Inactivated whole virus influenza vaccine and whole inactivated bacterial vaccines (pertussis, typhoid, cholera, and plague) are no longer available in the United States. Fractional vaccines include subunits (hepatitis B, influenza, acellular pertussis) and toxoids (diphtheria, tetanus). A subunit vaccine for Lyme disease is no longer available in the United States. A vaccine containing the capsid protein (L1) of human papillomavirus may be available in the future. Polysaccharide Vaccines Polysaccharide vaccines are a unique type of inactivated subunit vaccine composed of long chains of sugar molecules that make up the surface capsule of certain bacteria. Pure polysaccharide vaccines are available for three diseases: pneumococcal disease, meningococcal disease, and Salmonella Typhi. A pure polysaccharide vaccine for Haemophilus influenzae type b (Hib)is no longer available in the United States. Principles of Vaccination 6
Principles of Vaccination polysaccharide vaccine is Pure Polysaccharide Vaccines vaccines are able to stimulate B cells without the assistance of T-helper cells.T-cell-independent antigens ‘g9t8em5ynrarageogenicn including polysaccharide vaccines,are not consistently No booster response immunogenic in children younger than 2 years of age. Young children do not respond consistently to tyimproved by s;repeat doses of polysaccharide vaccines do not cause a booster response Antibody induced with polysaccharide vaccines has less functional activity than that induced by protein antigens. This is because the predominant antibody produced in response to most polysaccharide vaccines is IgM,and little IgG is produced. red that the problem 11 a p cally ation cha mnmicnnmohca infants and antibody booster response to multiple doses of vaccine. conjugared polysacchride vacine was forH cine for pneumoce ase wa Recombinant Vaccines .Thes may so be oduced by recomhinant vaccines three netically engineered vaccines are currently available in the United States.Hepatitis B vaccines are produced by insertion of a segment of the hepatitis B virus gene into the gene of a yeast cell.The cteria tha ave be to no asopharynx not in theung
1 The immune response to a pure polysaccharide vaccine is typically T-cell independent, which means that these vaccines are able to stimulate B cells without the assistance of T-helper cells. T-cell–independent antigens, including polysaccharide vaccines, are not consistently immunogenic in children younger than 2 years of age. Young children do not respond consistently to polysaccharide antigens, probably because of immaturity of the immune system. Repeated doses of most inactivated protein vaccines cause the antibody titer to go progressively higher, or “boost.” This is not seen with polysaccharide antigens; repeat doses of polysaccharide vaccines do not cause a booster response. Antibody induced with polysaccharide vaccines has less functional activity than that induced by protein antigens. This is because the predominant antibody produced in response to most polysaccharide vaccines is IgM, and little IgG is produced. In the late 1980s, it was discovered that the problems noted above could be overcome through a process called conjugation, in which the polysaccharide is chemically combined with a protein molecule. Conjugation changes the immune response from T-cell independent to T-cell dependent, leading to increased immunogenicity in infants and antibody booster response to multiple doses of vaccine. The first conjugated polysaccharide vaccine was for Hib. A conjugate vaccine for pneumococcal disease was licensed in 2000. A meningococcal conjugate vaccine was licensed in 2005. Recombinant Vaccines Vaccine antigens may also be produced by genetic engineering technology. These products are sometimes referred to as recombinant vaccines. Three genetically engineered vaccines are currently available in the United States. Hepatitis B vaccines are produced by insertion of a segment of the hepatitis B virus gene into the gene of a yeast cell. The modified yeast cell produces pure hepatitis B surface antigen when it grows. Live typhoid vaccine (Ty21a) is Salmonella Typhi bacteria that have been genetically modified to not cause illness. Live attenuated influenza vaccine has been engineered to replicate effectively in the mucosa of the nasopharynx but not in the lungs. Principles of Vaccination 7
Principles of Vaccination Selected References Ada G.The immunology of vaccination.In:Plotkin SA
1 Selected References Ada G. The immunology of vaccination. In: Plotkin SA, Orenstein WA. Vaccines. 4th ed. Philadelphia, PA: Saunders, 2003:31–45. Principles of Vaccination 8
General Recommendations on Immunization General Recommendations on Immunization 2 in vaccination prac mo th the General Recommendations on Immunization Recommendations of the Advisory Committee on s.Tes and the eAmerican Academy of -5w :51(R n2006. toe hould have aPorandbemrheaeneneeopyof downloaded riming and Spacing of Vaccines npn Vaeeme 7oe2&ngte86eaheangbod Specific circumstances that are commonly encountered in pei of the same accine of different vaccines,and the interval between subsequent doses of the same vaccine. General Rule Inactivated vaccines generally are not affected by circulating antibody to the antigen. Live attenuated vaccines may be affected by circuing antibody to the antigen. Antibody-Vaccine nteractions toavaccine antigen the vaccine.The moun of e produced by 9
2 General Recommendations on Immunization This chapter discusses issues that are commonly encountered in vaccination practices. A more thorough discussion of issues common to more than one vaccine can be found in the General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices and the American Academy of Family Physicians. These recommendations are revised every 3–5 years as needed; the most current edition was published in February 2002 (MMWR 2002;51(RR–2):1–36). A revised document is expected to be published in 2006. All providers who administer vaccine should have a copy of this report and be familiar with its contents. It can be downloaded from the MMWR website or ordered in print version from the Centers for Disease Control and Prevention. Timing and Spacing of Vaccines The timing and spacing of vaccine doses are two of the most important issues in the appropriate use of vaccines. Specific circumstances that are commonly encountered in immunization practice are the timing of antibody-containing blood products and live vaccines (particularly measles vaccine), simultaneous and nonsimultaneous administration of different vaccines, and the interval between subsequent doses of the same vaccine. Antibody–Vaccine Interactions The presence of circulating antibody to a vaccine antigen may reduce or completely eliminate the immune response to the vaccine. The amount of interference produced by circulating antibody generally depends on the type of vaccine administered and the amount of antibody. Inactivated antigens are generally not substantially affected by circulating antibody, so they can be administered before, after, or at the same time as the antibody. Simultaneous administration of antibody (in the form of immune globulin) and vaccine is recommended for postexposure prophylaxis of certain diseases, such as hepatitis B, rabies, and tetanus. General Recommendations on Immunization 9 Inactivated vaccines generally are not affected by circulating antibody to the antigen. Live attenuated vaccines may be affected by circulating antibody to the antigen. General Rule
General Recommendations on Immunization Antibody and Live Vaccines Live vaccines must replicate in order to cause an immune response.Antibody against parenteral (injected)live vaccine Action antigen may interfere with neasles-mumpsrubel or vanc Antibody not interfere with viral replication.If the live vaccine is incubation period)befory to at at leas egiving the should be re the ne o of MMR or varicella waned interval between an antibody-containing product and MMR or varicella e recommen intervals between (MMR the General Recommendations on Imr tion.The inter a between administration of an antibody product and MMR or varicella vaccination can be as long as 11 months. Although passively the low dose of anti-Rho(D) lobulin administered to ostpartum won n has not been 7B strain ring age women MMR e should not be dela -h(D)ooher uctthe very and munity to rubella sary,to measles. Oral typhoid,and yellow fever vaccines are not affected by lood products. few icans are im e ro vellow fever or Antibody for Prevention of RSV typhoid.Consequently,donated blood products in the RSV-IG(RespiGam) United States do not contain a significant amount of Containotherantibode body on live attenuate Two antibody products are available for the prevention of respiratory syncytial virus(RSV)infection in infants and Contains only RSV antibody young children.RSV-IG(RespiGam)is an intravenous 10
2 Live vaccines must replicate in order to cause an immune response. Antibody against parenteral (injected) live vaccine antigen may interfere with replication. If a live parenteral vaccine (measles-mumps-rubella [MMR] or varicella) must be given around the time that antibody is given, the two must be separated by enough time so that the antibody does not interfere with viral replication. If the live vaccine is given first, it is necessary to wait at least 2 weeks (i.e., an incubation period) before giving 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 given before a dose of MMR or varicella vaccine, it is necessary to wait until the antibody has waned (degraded) before giving the vaccine to reduce the chance of interference by the antibody. The necessary interval between an antibody-containing product and MMR or varicella vaccine depends on the concentration of antibody in the product. A table listing the recommended intervals between administration of antibody products and live vaccines (MMR and varicella) is included in Appendix A and in the General Recommendations on Immunization. The interval between administration of an antibody product and MMR or varicella vaccination can be as long as 11 months. Although passively acquired antibodies can interfere with the response to rubella vaccine, the low dose of anti-Rho(D) globulin administered to postpartum women has not been demonstrated to reduce the response to the RA27/3 strain rubella vaccine. Because of the importance of rubella immunity among childbearing age women, postpartum vaccination of rubella-susceptible women with rubella or MMR vaccine should not be delayed because of receipt of anti-Rho(D) globulin or any other blood product during the last trimester of pregnancy or at delivery. These women should be vaccinated immediately after delivery and, if possible, tested 3 months later to ensure immunity to rubella and, if necessary, to measles. Oral typhoid, and yellow fever vaccines are not affected by the administration of immune globulin or blood products. They may be given simultaneously with blood products, or separated by any interval. These vaccines are not affected because few North Americans are immune to yellow fever or typhoid. Consequently, donated blood products in the United States do not contain a significant amount of antibody to these organisms. The effect of circulating antibody on live attenuated influenza vaccine is not known. Two antibody products are available for the prevention of respiratory syncytial virus (RSV) infection in infants and young children. RSV-IG (RespiGam) is an intravenous 10 General Recommendations on Immunization