1 Basic Concept of Vaccination 1.1 Definition of vaccines What is a vaccine? Type of vaccine Examples The word “vaccine” originates from the Latin Variolae vaccinae Live-attenuated Measles, Mumps, Rubella, (cowpox), which Edward Jenner demonstrated in 1798 could Varicella zoster prevent smallpox in humans. Today the term ‘vaccine’ applies Inactivated Hepatitis A, Influenza, Pneumococcal to all biological preparations, produced from living organisms, polysaccharide that enhance immunity against disease and either prevent Recombinant sub-unit Hepatitis B (prophylactic vaccines) or, in some cases, treat disease Toxoid Tetanus, Diphtheria (therapeutic vaccines). Vaccines are administered in liquid form, either by injection, by oral, or by intranasal routes. Conjugate Pneumococcal, meningococcal, polysaccharide-protein Haemophlius influenzea type b (Hib) Vaccines are composed of either the entire disease-causing TABLE 1. EXAMPLES OF VACCINES BY TYPE microorganism or some of its components. They may be constructed in several ways (See Figure 1): • From living organisms that have been weakened, usually from cultivation under sub-optimal conditions (also called attenuation), or from genetic modification, which has the effect of reducing their ability to cause disease; • From whole organisms that have been inactivated by chemical, thermal or other means; • From components of the disease-causing organism, such as specific proteins and polysaccharides, or nucleic acids; • From inactivated toxins of toxin-producing bacteria; • From the linkage (conjugation) of polysaccharides to proteins (this increases the effectiveness of polysaccharide vaccines in young children) (See Figure 2). Examples of each type of vaccine are shown in Table 1. 4 | VACCINE FACT BOOK 2012 LIVE-ATTENUATED VACCINE FLUIDS AND SUB-OPTIMAL CONDITIONS ADDITIVES PURIFICATION DISEASE-CAUSING AGENT ATTENUATION FORMULATION VACCINE INACTIVATED VACCINE THERMAL OR CHEMICAL TREATMENT FLUIDS AND ADDITIVES PURIFICATION DISEASE-CAUSING AGENT INACTIVATION FORMULATION VACCINE RECOMBINANT SUB-UNIT VACCINE FLUIDS AND ADDITIVES PROTEIN SUB-UNIT PURIFICATION GENE EXPRESSION CELL DISEASE-CAUSING AGENT PROTEIN EXPRESSION FORMULATION VACCINE TOXOID VACCINE CHEMICAL TREATMENT FLUIDS AND INACTIVATED ADDITIVES TOXIN 2011 - TOXIN PURIFICATION DISEASE-CAUSING AGENT INACTIVATION FORMULATION VACCINE PRODUCING TOXIN FIGURE 1 VACCINE FACT BOOK FACT VACCINE FIGURE 1. TYPES OF VACCINE CONSTRUCTS 5 VACCINE FACT BOOK 2012 | 5 HUMORAL RESPONSE HUMORAL RESPONSE PROTEIN AND IMMUNE AND IMMUNE VACCINE MEMORY IN INFANTS MEMORY IN ADULTS HUMORAL RESPONSE HUMORAL RESPONSE POLYSACCHARIDE NO IMMUNE MEMORY AND IMMUNE VACCINE IN INFANTS MEMORY IN ADULTS HUMORAL RESPONSE HUMORAL RESPONSE CONJUGATE AND IMMUNE AND IMMUNE VACCINE MEMORY IN INFANTS MEMORY IN ADULTS FIGURE 2 unit vaccine, conjugated polysaccharide vaccine, recombinant protein vaccine, and inactivated FIGURE 2. CONJUGATION OF POLYSACCHARIDESviral vaccine respectivelyTO PROTEIN (SEE FigureS 3 ). INCREASES THE InEFFECTIVENESS addition to combining OF severalPOLYSACCHARIDE serotypes of a disease-VACCINES IN YOUNG CHILDREN Vaccines 2011 may also - causing organism in a single vaccine (e.g. 13-valent contain antigens VIRAL BACTERIAL pneumococcal conjugate vaccine), vaccines against against several types differentIn addition disease-causing to combining organisms several can beserotypes combined ofto a disease-causing organism in a single vaccine (or serotypes) of the TOXOIDS same disease-causing provide protection against several different diseases. These (e.g. 13-valent pneumococcal conjugate vaccine), vaccines against different disease-causing organism, providing RECOMBINANT TETANUS combination vaccines may contain different types of vaccines. protection against organisms can be combined to provide protection againstPROTEIN several different diseases. These Combination vaccines against different diseases such as DIPHTHERIA each type. Polio and HEPATITIS B diphtheria,combination tetanus, vaccines pertussis, may Heamophilus contain influenzae different type types of vaccines. Combination vaccines against influenza vaccines VACCINE SUBUNIT b, Hepatitis B, and polio, are commonly used in childhood each protect against 3 different diseases such as diphtheria, tetanus, pertussis, Heamophilus influenzaePROTEIN type b, immunization schedules. These vaccines incorporate both INACTIVATED types of virus, and Hepatitis B, and polio, are commonly used in childhood immunization schedules.PERTUSSIS These some bacterial viral and bacterial vaccines and contain toxoids, purified POLIO vaccines like proteinvaccines sub-unit incorporate vaccine, conjugated both viral polysaccharide and bacterial vaccine, vaccines and contain toxoids, purified proteinPROTEIN sub - pneumococcalBOOK FACT VACCINE vaccine recombinant protein vaccine, and inactivated viral vaccine CONJUGATE protect against up to respectively (See Figure 3). HAEMOPHILUS 23 different serotypes INFLUENZAE TYPE B of Streptococcus 6 pneumoniae. A full list of vaccines FIGUREFIGURE 3. 3 COMMON. COMMON COMBINATION COMBINATION PEDIATRIC PEDIATRIC VACCINE VACCINE CONTAINING CONTAINING MULTIPLEMULTIPLE ANTIGENS ANTIGENS OF OF MULTIPLE MULTIPLE VACCINE VACCINE TYPES TYPES according to their type can be seen in Table 6 | VACCINE FACT BOOK 2012 4 , SECTION 1.2. What does a vaccine contain? In addition to the bulk antigen that goes into a vaccine, vaccines are formulated (mixed) with other fluids (such as water or saline), additives or preservatives, and sometime adjuvants. Collectively, these ingredients are known as the excipients. These ensure the quality and potency of the vaccine over its shelf-life. Vaccines are always formulated so as to be both safe and immunogenic when injected into humans. Vaccines are usually formulated as liquids, but 2011 - may be freeze-dried (lyophilized) for reconstitution immediately prior to the time of injection. Preservatives ensure the sterility of the vaccine over the period of its shelf-life. Preservatives may be used to prevent contamination of multi-dose containers: when a first dose of vaccine is extracted from a multi-dose container, a preservative will protect the remaining product from any bacteria that may be introduced into the container. Or, in some cases, preservatives may be added during manufacture to prevent microbial contamination. Preservatives used in vaccines are non-toxic in the amounts used and do not diminish the potency of vaccines. But not all VACCINE FACT BOOKFACT VACCINE preservatives can be used in all vaccines. Some preservatives will alter the nature of some 7 1 Basic Concept of Vaccination Vaccines may also contain antigens against several types In addition to preservatives, some vaccines contain adjuvants. (or serotypes) of the same disease-causing organism, Adjuvants enhance the immune effect of the vaccine antigen, providing protection against each type. Polio and influenza but do not themselves act as antigens. Aluminum salts are vaccines each protect against 3 types of virus, and some the most commonly used adjuvant for vaccines. Adjuvanted bacterial vaccines like pneumococcal vaccine protect against vaccines may have a slightly higher rate of adverse reactions, up to 23 different serotypes of Streptococcus pneumoniae. including pain at the injection site, malaise and fever. A list of commonly adjuvanted childhood vaccines is shown in Table 3. A full list of vaccines according to their type can be seen in Table 4, Section 1.2. Adjuvanted Vaccine Type of Adjuvant What does a vaccine contain? Hepatitis A Aluminum salt Hepatitis B Aluminum salt In addition to the bulk antigen that goes into a vaccine, Diphtheria, Tetanus, Aluminum salt vaccines are formulated (mixed) with other fluids (such as acellular Pertussis water or saline), additives or preservatives, and sometimes combinations (DTaP or adjuvants. Collectively, these ingredients are known as the Tdap) excipients. These ensure the quality and potency of the Haemophilus influenzae Aluminum salt vaccine over its shelf-life. Vaccines are always formulated type b (Hib) so as to be both safe and immunogenic when injected into Human Papilloma Virus Aluminum salt or AS04 (aluminum salt humans. Vaccines are usually formulated as liquids, but may (HPV) and monophospholipid A) be freeze-dried (lyophilized) for reconstitution immediately Pneumococcal conjugate Aluminum salt prior to the time of injection. Japanese encephalitis Aluminum salt H1N1 influenza MF59 (oil in water emulsion) [one Preservatives ensure the sterility of the vaccine over the vaccine] period of its shelf-life. Preservatives may be used to prevent TABLE 3. EXAMPLES OF ADJUVANTED VACCINES2 contamination of multi-dose containers: when a first dose of vaccine is extracted from a multi-dose container, a preservative will protect the remaining product from any bacteria that may be introduced into the container. Or, in some cases, preservatives may be added during manufacture to prevent microbial contamination. Preservatives used in vaccines are non-toxic in the amounts used and do not diminish the potency of vaccines. But not all preservatives can be used in all vaccines. Some preservatives will alter the nature of some vaccine antigens. Preservatives commonly used in vaccine formulation are shown in Table 2. Although there is no evidence of harm caused by any preservative, vaccines in the US and Europe have, for the most part, been free of thimerosal (or contain only trace quantities) for several years now. And some newer vaccines may not contain