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Medical Microbiology Third SemesterIntroduction History Designing of vaccines Mechanism of action Types of vaccines : Introduction History Designing of vaccines Mechanism of action Types of vaccines VACCINES Contents:Introduction: Introduction Vaccines:- Vaccine is an immuno-biological substance designed to produce specific protection against a given disease . It stimulates the production of protective antibody and other immune mechanism. Vaccination:- Vaccination is the process of administration of a substance called vaccine to induce immunity against a disease.HISTORY: HISTORY EDWARD ANTHONY JENNER (1749-1823) He was an English scientist who studied in his natural surroundings Berkeley . Jenner is widely credited as the pioneer of Smallpox vaccine, and is sometimes referred to as a “Father of Immunology” . Jenner’s discovery has saved more lives than the work of any other man.LOUIS PASTEUR(1822-1895): LOUIS PASTEUR(1822-1895) He is also know as “Father of Microbiology”. He coined the term Vaccine . He introduced attenuated live vaccine for prophylactic use. He convincingly demonstrated the protective role of anthrax vaccine in public experiment (1881) . Pasteur’s development of a vaccine for hydrophobia marked a milestone of immunization in medicine. The Pasteur institute Paris was built by public contribution for the preparation of vaccine and for the investigation of infectious diseases.DESIGNING OF VACCINE: DESIGNING OF VACCINE A vaccine is substance used to generate active immunity. It is usually either a modified whole pathogen or its product or its components. The overall aim of vaccination is to give adequate and long lasting immunity against the disease for which it is used. Other consideration: Safety Efficacy Memory Route of administration Storage condition Long self life Affordability Incubation period The site at which immunity is producedMechanism of action:: Mechanism of action: The disease causing organisms contain proteins called “antigens” which stimulate the immune response. The resulting immune response is multi-fold and includes the synthesis of proteins called “antibodies”. These proteins bind to the disease causing organisms and lead to their eventual destruction. In addition , “memory cells” are produced in an immune response. These are cells which remain in the blood stream , sometimes for the life span of the host , ready to mount a quick protective immune response against subsequent infections with the particular disease causing agent which induce their protection.TYPES OF VACCINE: TYPES OF VACCINE Whole organism: A . Killed or inactivated: In these vaccines, the whole organism ,killed by heat, chemicals or radiation, is used as antigen . Heat ,in this respect ,is not a suitable mode of inactivation as it destroys the epitopes as well. Formaldehyde and alkylating agents are commonly used. These vaccines are good at producing humoral but cellular response is poor . They also require multiple boosters and higher doses because they are weak immunogens . Examples: Bacterial:- Typhoid , Whooping cough ,(pertusis). Viral:- Salk polio, Influenza , Rubella, Hepatitis B, Japanese B encephalitis.PowerPoint Presentation: Advantages: Safety and stability. They can be given in combination as polyvalent vaccines . There is no danger of spread of virus from the vaccine. Disadvantages: Multiple injections are needed . Booster doses may be required at intervals to revive waning immunity. These vaccines have to be given by injection, therefore, local (IgA ) immunity fails to develop. Cell mediated immunity is not induced.PowerPoint Presentation: B . Live attenuated vaccine: These consist of live but drastically weakened and a virulent organism . Attenuation is usually done by grouping organism in abnormal conditions different than those found in the natural host. The organism undergoes mutations and acquires the ability to survive in altered conditions but loses the ability to produce disease in the natural host. Examples: Bacterial:- BCG Viral:- Mumps, Sabin polio, chicken pox, measles, rubella, yellow fever, varicella, & measles-mumps-rubella(MMR).PowerPoint Presentation: Advantages: A single dose of live attenuated vaccine is usually sufficient because they multiply in the host and provide continuous antigenic stimulation resulting in more lasting immunity than killed vaccine . They may be administered by the route of natural infection so that local immunity is induced. They induce a wide spectrum of immunogens against the whole range of microbial antigens. They also induce cell mediated immunity(CMI). They can, in general, be prepared more economically and administered more conveniently for mass immunisation.PowerPoint Presentation: Disadvantages: There is risk, however remote , of reversion of virulence. The vaccine may be contaminated with potentially dangerous viruses. E.g. Oncogenic viruses Live vaccines are heat labile and they have to be under strict refrigeration. Interference by preexisting microorganisms may sometimes prevent a good immunological response following vaccination. Some live vaccines may cause local but remote complications. The organism s may spread from vaccinees to contact and this is a serious danger in some situation(as in rubella,if the vaccine strain is teratogenic).PowerPoint Presentation: Differences: NATURE LIVE ATTENUATED INACTIVATED OR KILLED Nature Live but avirulent organism Virulent but inactivated organisms Reversion to virulent form Possible Not possible Immune response Good humoral and cellular Good humoral response but poor cellular response Stability Less stable More stable Immunogenicity Good Poor Booster requirement Generally not, only single dose Multiple dosesPowerPoint Presentation: Purified macromolecular vaccines: These vaccines use specific purified macromolecules derived from pathogens to avoid the risk associated with whole organism. A. Inactivated exotoxins/ toxoid vaccines:- The exotoxin produced by the pathogens is chosen as an immunogen . It is inactivated by treatment with formaldehyde to form toxoid. The anti-toxoid antibodies produced after vaccination it to produce immunity. But these antibodies do not bind the microbe and so do not produce immunity against the microbe.PowerPoint Presentation: B. Polysaccharide vaccines:- M any pathogens have their virulence attributed to the capsular polysaccharide components. These vaccines do not activate TH cells but only B cells. Hence very poor memory is produced. Only IgM antibodies are produced .These are good opsonising antibodies and are given to high risk individuals like infants, elderly and immunodeficient persons. A way to improve the immune response is to combine the polysaccharide antigen with a protein carrier which could induce the TH cells also . Such vaccines are some times referred to as conjugate vaccines. E.g.:- H . influenza , N . meningitids , S . pneumonaePowerPoint Presentation: C. Recombinant antigen vaccines:- The antigen is genetically engineered. E.g. the gene encoding the antigen is cloned and expresses in a suitable cell culture system . The harvested antigen is used as vaccine. E.g. Hepatitis B vaccine Recombinant vector vaccine: The gene encoding the immunogen is introduced into the live attenuated vector to produce a recombinant vector. this is then used as vaccine. On inoculation into the host , vector gene, including the antigen gene , are expressed. The expressed antigen produces an immune response.PowerPoint Presentation: Commonly used vectors are the attenuated strains of small pox virus ( Vaccinia virus) , Canary pox virus and Salmonella typhimurium. Advantages:- Salmonella bacteria infects GUT mucosa and produces IgA. These vaccines produce good immunity, memory , and specific Tc cells. DNA Vaccines: In this approach bacterial plasmid DNA bearing the gene sequence of Ag is injected directly into the muscle of the host. DNA is taken up by the muscle cells and expressed by them. The expressed protein acts as Ag and produces immunity.PowerPoint Presentation: Advantages:- The DNA vaccines are very effective in stimulating both AMI and CMI responses. The vaccination occurs in a very natural ways as microbes would do after infection. The Ag protein is expressed within the recipient and does not undergo any modification. The DNA vaccine does not require refrigeration during storage, handling or transportation. Disadvantage:- Only protein antigens can be used by this technique.PowerPoint Presentation: Synthetic peptide vaccines: The basic idea in this approach is to use synthetic peptides corresponding to B &T cell epitopes of an Ag as vaccines. These epitopes are identified in a given Ag by analysing its primary structure. Advantage:- They do not use live organisms and hence they are safe. Disadvantages:- Poor immunogen due their small size. No memory is developed and cellular response is also poor.PowerPoint Presentation: Multivalent subunit vaccines: These are the synthetic vaccines containing multiple peptides antigens bound on a support system. They may contain multiple copies of a single antigenic peptide instead of multiple antigen. One way is to prepare a solid matrix Ag- Ab complex (SMAA).In this monoclonal Abs are attached to the solid support matrix . To these Abs are then bound antigenic peptide containing specific T and B cell epitopes . This is then used as Ag. Advantages:- Being particulate in nature and having both T and B cell epitopes, they act as a strong immunogen eliciting good humoral, cellular and memory response. Examples:- Influenza, Hepatitis B , HIV, Measles etc.Immunization schedule: I mmunization schedule Contents: Universal immunization programme Implementation of immunization programme in India Rationale of immunization National immunization schedule(INDIA) Individual immunization Hazards of immunizationUniversal immunization programme: U niversal immunization programme In May 1974, the WHO officially launched a global immunization programme , known as Expanded Programme on Immunization (EPI) to protect all children of the world against six vaccine-preventable diseases , namely-diphtheria , whooping cough , tetanus , polio , tuberculosis and measles by the year 2000. The programme is now called Universal Child Immunization , 1990- that’s the name given to a declaration sponsored by UNICEF as part of the United Nation’s 40 th anniversary in October 1985. It is aimed at adding impetus to the global programme of EPI.Implementaion of immunization programme in INDIA: I mplementaion of immunization programme in INDIA EPI was launched in India in January 1978. The India version, the Universal Immunization Programme , was launched on November 19 , 1985 and was dedicated to the memory of Smt. Indria Gandhi. EPI was adopted targeting 80% coverage of infants with Bacillus Calmette - Guerin (BCG) ,diphtheria , tetanus ,pertusis , polio and typhoid – paratyphoid vaccine.PowerPoint Presentation: EPI was revised as the Universal Immunization Programme (UIP) during 1985 -1990 targeting 100% coverage ; also typhoid - paratyphoid vaccine was dropped and measles vaccine was added. Tetanus toxoid vaccination of pregnant women was part of EPI and was retained in UIP. The National Technical Advisory Group on Immunization (NTAGI) was established in August 2001 by DFW . The NTAGI was intended to provide technical advice to inform decision making on both technical and operational matters pertaining to immunization and choice and scheduling of existing and planned vaccines. Rationale of Immunization : Rationale of Immunization The objective is to produce , without harm to the recipient , a degree of resistance sufficient to prevent a clinical attack of the natural infection and to prevent the spread of infection to susceptibles in the community. There is therefore both a personal gain from being immunized and a public health benefit to the population. The degree of resistance conferred may not protect against an overwhelming challenge , but exposure may help to boost immunity.Estimated annual deaths worldwide of children under 5 years of age , pathogen: Estimated annual deaths worldwide of children under 5 years of age , pathogen *Signifies pathogen for which an effective vaccine exist. #A licensed vaccine is being tested for possible side effects. Pathogens Deaths (thousands) Pneumococcus * 841 Measles 530 Haemophilus (strain a-f)# 945 Rotavirus# 800 Malaria 700 HIV 500 RSV 500 Pertussis 285 Tetanus 281 Tuberculosis 100National Immunization schedule (INDIA) : N ational Immunization schedule (INDIA) Age Vaccine At birth BCG , OPV – O 6 weeks BCG – 2 , DPT – 1 , OPV – 1 10 weeks DPT – 2 , OPV -2 14 weeks DPT – 3 , OPV – 3 9 months Measles 16 – 24 months DPT , OPV 5 – 6 years (School entry) DT3 10 years TT 4 16 years TT 4 For pregnant women TT -1 or booster One month after TT – 1 TT-2PowerPoint Presentation: Note: For institutional births only. OPV is additional , and not to be counted for primary course of 3 doses starting at 6 Weeks. Only for infants not given BCG at birth. A second dose of DT to be given to children with no documentary evidence or history of primary DPT immunization. A second dose of TT to be given after one month to those with no record or history of prior DPT , DT or TT immunization. For prevention of tetanus in the neonate primarily ,but also in motherIndividual Immunization:: Individual Immunization: Vaccines offered under national immunization programmes are limited by economic considerations and so some important vaccines may be omitted because they are costly. These may be supplemented by individual initiative whenever possible. The immunizations recommended for individuals at risk of acquiring specific infections include: Hepatitis B vaccine , which should be given to as many children and adults as possible by individual immunization or through voluntary agenciesPowerPoint Presentation: Measles –mumps-rubella (MMR) vaccine , which should be given at 16-24 months or later to reinforce immunity against measles and also to protect against mumps and rubella. Varicella vaccine , which has been recommended for general use for prevention of varicella and herpes zoster. The live attenuated vaccine is recommended as a single subcutaneous dose in children (9 months – 12 years) and as two doses (interval of at least 6 weeks) in older individuals. The typhoid vaccine; the original typhoid vaccine is not widely used now due to frequent adverse reactions. Two recent versions , the live , oral Gal-E mutants vaccine and the injectable purified Vi polysaccharide vaccine ,offers prolonged protection and are free from reactions; they are recommended for immunization of children above the age of 5 years.Hazards of immunisation: Hazards of immunisation No immune response is entirely free from the risk of adverse reactions or remote sequel . The adverse reactions that may occur may be grouped under following headings: Reactions inherent to inoculation: Local:- Pain , swelling, redness , tenderness , and development of small nodule at the site of injection. General:- Fever , malaise , headache and other constitutional symptoms.PowerPoint Presentation: Reactions due to faulty technique: Faulty production of vaccine . To much vaccine given in one dose. Improper immunization site or route. Vaccine reconstituted with incorrect diluents , wrong amount of diluent used . Vaccine stored incorrectly. Contraindication ignored. Use of improperly sterilized syringes and needles.PowerPoint Presentation: Reactions due to hypersensitivity: Anaphylactic shock . Serum sickness. Neurological involvement: Neuritic manifestations may be seen after the administration of serum or vaccine. The well known examples are the post vaccinial encephalitis and encephalopathy following administration of anti rabies and small pos vaccines. The out come of neurological involvement could be fatal.PowerPoint Presentation: Provocative reactions: Occasionally following immunization there may occur a disease totally unconnected with immunizing agent (E.g. , provocative polio after ATP or PTAP administration against diphtheria) . The mechanism seems to be that the individual is harbouring the infectious agent and the administration of the vaccine shortens the incubation period and produces the disease or what may have been otherwise only a latent infection is converted into a clinical attack. Others : These may comprise damage to the foetus (e.g. , with rubella vaccination).Refrences:: Refrences: Kuby Immunology(6 th edition) Medical Microbiology - David Greenwood et al (16 th edition) Essentials of immunology – S.K.GUPTA Preventive and social medicine – K. Park (18 th edition) Textbook of Microbiology – Ananthanarayan and (8 th edition) Paniker’s A text book of microbiology – Prof. C. P. 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