INFECTION AND IMMUNITY
Major Areas Definitions
of Immunity Antibody dependent protective mechanisms Complement mediated protection Cell mediated protective mechanisms Parasite and microbe evasion immune stratagems Vaccines
Infection and Immunity Infants
depend on maternal protective antibodies, principally IgG, in the first 6-9 months in life. sIgA secretion in human colostrums and milk confers maternal immunity to suckling infants. IgG crosses the placenta from the eighth week of gestation by passive and active transmission. Maternal IgG – Fc receptors on the placenta syncytiotrophoblasts facilitate the active transfer of the IgG antibodies. Maternal derived antibodies interfere with vaccination of infants (measles, mumps and rubella infections).
Immunity Profile Sterile Immunity State of protection when all the infectious agents are eliminated in the host. Premunition Low-grade infection providing protection in subsequent asymptomatic chronic infections Occurs in several infections, malaria and diphtheria (Corynebacterium diphtheria).
Immunity Profile cont Concomitant Immunity Age dependent resistance to reinfection directed at the early larval stages Adult forms unaffected (schistosomiasis, filariasis and echinococcosis diseases). Herd Immunity Community protection or resistance conferred to susceptible proportion of individuals in a vaccinated population (>=95%) and Infection does not result in an epidemic
Innate Determinants of Immunity Genetic
Determinants Physical Barriers Soluble Factors Cellular Components
Innate Mediated Factors Innate immune responses involve
Genetics, anatomical barriers, bacterial antagonisms Pattern-recognition receptors (PRR)
Soluble factors Nonspecific defense chemicals, complement proteins
Innate Mediated Factors cont Cellular (cells) components Neutrophils, monocytes and macrophages Basophils, mast cells and eosinophils release inflammatory mediators. Alternative pathway of complement activation Provides defense against gramnegative bacteria Interferons inhibit viral replication and activate inflammatory cells.
Genetic determinants of malaria immunity Innate protection associated with Negative
Duffy (a-b) blood groups (Plasmodium vivax); Sickle cell trait A/S and glucose-6phosphate (G-6-PO4) dehydrogenase deficiency. Plasmodium infected erythrocytes highly susceptible to toxic oxygen intermediates or radicals. Intracellular development of P.falciparum in G-6-PO dehydrogenase deficient
Physical Barriers To Infection Barrier site (first line of defense) Skin sweat
Activity
Skin and GI tract natural fauna GI tract
Compete for niches
Lung tracheal cilia
Mucociliary elevation
Nasopharynx, mucus and saliva, eye tears
Flushing, organic acids
Peristalsis, low pH, bile acid, flushing, antibacterial peptides
Flushing, lysozymes
Antimicrobial Peptides Defensins and cathelicidins Protect against microbes Secreted by epithelial cells (skin, GIT, genitourinary tract and nasal passages and lungs) and recruited leukocytes (neutrophils). Punch lethal holes facilitated by their positive charges in penetrating the bacterial membranes. Synergistically with cathelicidins confer protection against microbes.
Events in Phagocytosis involve: (1) Organism (bacterium) attaches to pseudopodia (long membrane evaginations) leading to (2) Ingestion occurs forming phagosome that (3) Fuses with lysosome releasing lysosomal enzymes into phagosome and (4) Digestion of ingested organism leading to (5) Release of products from the cell.
Microbicidal Mechanisms Associated with Assembly of NADPH oxidase Upregulation of cytochrome B558 in activated neutrophils Production of ROI (superoxides, hydrogen peroxide) Hydrogen peroxide reaction with chlorides o Generates hypochloric acid (microbicidal agent) and free chlorine
Macrophage Derived Factors and Activities Products
Metabolites: Reactive oxygen intermediates (ROI) Reactive nitrogen intermediates (RNI) Eicosanoids, prostaglandins leukotrienes IL-1, TNF-α, IL-6 Platelet activating factor IFN-α IL-10 IL-12, IL-18 TGF- β
Cytokines:
Activity
Inflammation and intracellular killing Inflammation and intracellular killing Regulation, inflammation Recruitment Inflammation and activation of platelets. Th1 activation Th1 suppression, Th2 activation Activation of NK and T cells Inflammation, tissue repair
Adhesion molecules: Fibronectin Thrombospondin
Opsonisation Adhesion, phagocytosis
Complement: C3b, C4b and C2b
Opsonisation
Enzymes: Lysozyme Collagenase, elactase
Degrades bacterial cell walls Matrix catabolism
Complement Mediated Protection C3b-R
and C4b-R mediated opsonization and phagocytosis C3b-R and C4b-R potentiation of ADCC MAC (C5b-9) mediated lysis and neutralization
Complement AssociatedPhagocytosis C3b-R and C4b-R mediated opsonization and phagocytosis effective protective mechanism against Gram-positive bacterial infections Streptococcal (S. pyogenes and S.pneumoniae) Staphylococcal (S. aureus) Meningococcal (N.meningitidis) Plaque (Y.pestis); cryptococcal and anthrax (B.anthracis). C3b and C4b potentiate ADCC mechanisms against various pathogens.
Membrane attack complex activity Responsible for Neutralization of gram-negative bacteria o
E. coli, S. typhi, S. dysenteriae, N. meningitides, N. gonorrhea),
Damage o o o
of
Filarial worms (microfilariae), Tapeworms (protoscolices of E. granulosus) and Amastigotes of leishmania parasites.
Antibody Dependent Mechanisms Inhibition
of epithelial attachment Neutralization activity Fc-R mediated opsonization and phagocytosis Fc-R potentiation ofADCC
importance of antibody – mediated mechanisms
Depend on host-parasite interactions. Acquired resistance gradual and influenced by the parasite development stages, species and dosages. Exposure to plasmodium parasites induces partial immunity dependent on sporozoite, inoculum,species and stage specific. Anti-circumsporozoite protection ineffective against blood stage infective merozoites and vice versa.
Inhibitory responses
In early schistosomiasis anti-egg stage blocking antibodies inhibit protective immunity against cercariae. o
Young schistosomiasis patients susceptible to cercarial infectivity despite high anti-egg antibodies.
Inhibition of Epithelial Cell Attachment sIgA and IgG prevent adherence onto sub-epithelial mucosal surfaces by bacterial infections Cholera
(Vibrio cholera); Gonococcal (Neisseriae gonorrhoea); Streptococcal (Streptococcus pneumoniae); Dysentery (Shigella dysenteriae);
Neutralizing Antibody Activity Live
microorganisms release diffusible exotoxins, neutralized by sIgA and IgG antibodies. IgG potent anti-toxin antibodies in tissue spaces IgG mediate neutralizing activities by binding exotoxin (antigenic determinants) or receptors on target cells. In poliomyelitis, most neutralizing antibodies directed at virus protein polypeptide 1 (VP1) In parainfluenza virus and adenovirus infections raised against haemagglutinin and
Neutralizing Antibody Activity cont Mechanism effective against various pathogens o Gram-negative bacteria (S. typhi, K. pneumoniae, V. cholerae, E. coli, S.dysenteriae); o Gram-positive bacteria (Cl.tetani, S. pyogenes, C. diphtheria and S.aureus) o Viruses( CMV, RSV, parainfluenza, HBV and HIV. o Infective protozoan stages (merozoites and sporozoites) o Anti-merozoite antibodies neutralize acute manifestation of malaria.
Neutralizing Antibody Activity cont Species specific protective IgG in multiple malaria infections Inhibit
invasion of normal erythrocytes thru blocking glycophorin receptors (merozoite receptors on erythrocytes) Prevent infected erythrocyte entry into vascular endothelium (heart, brain and kidney venules parasite sequester to avoid spleen immune attack)
Ab Mediated Opsonization and Phagocytosis Opsonic antibodies facilitate Fc-R mediated phagocytosis important against bacterial infections o Streptococcal
(S. pneumoniae) o Staphylococcal meningococcal (N.meningitidis) o Plague (Yersinia pestis), o Cryptococcal (C. neoformans) and anthrax (Bacillus anthracis);
Opsonization and phagocytosis Protozoan
infections o Malaria (P.falciparum), o Trypanosomiasis (T.rhodesiense); Echinococcosis (E.granulosus protoscolices); Viral infections (HBV).
Antibody Dependent Cell Mediated Cytotoxicity (ADCC) Target
organism or parasite killing due to released cytotoxic factors o o o
Perforins, Lymphotoxins and Neutral serine proteases)
Eosinophil
derived cytotoxic peroxidase (EPO), eosinophil cationic protein (ECP) and major basic protein (MBP) mediate killing ADCC effective against helminthic infections o o
Schistosomulae (S. mansoni and S. haematobium) Microfilariae (W.bancrofti and Onchocerca volvulus) during natural oncocerciasis infections
Antibody Dependent Cellular Cytotoxity (ADCC) Mechanism: Cytotoxic cells express Fc-R for the Ig bound onto the target and damage it as explained in the text.
Cell Mediated Immunity (CMI) Mechanisms
Cell Mediated Immunity Mechanisms Cytotoxic
T lymphocytes (CTL) Macrophage mediated cytotoxicity NK cell cytotoxicity Delayed type hypersensitivity (DTH)
Cytotoxic T Cells (CTL) CTL mediate antigen – specific, class 1MHC – restricted cytotoxicity against All viruses, obligate intracellular bacteria (Chlamydia) and some protozoa (T. gondii). o Induce apoptosis targets and then dissociate to bind and kill other target cells. Specific CTL CD8 mediate protective immunity in o
o o
Viral and protozoan infections (influenza malaria) Influenza virus infected cells lysed by CTL.
and
CTL Cont Disease progression correlates with T cell responses and IgM-anti-HCV antibodies. Intracellular development of parasites P. falciparum inhibited by CTL and Cytokines (TNF, IL-6 and C-reactive proteins) Sporozoites induce CTL that o o
Recognize plasmodium parasite antigens on the surface of malaria infected hepatocytes Damaged by the parasite specific CD8+ CTL.
Macrophage Mediated Cytotoxicity CTL derived γ-IFN efficiently activate mφ to fuse their phagosomes and lysosomes more o
Increase synthesis of NO, ROI, antimicrobial peptides and IL-12.
Activated mφ increase phagocytic, metabolic oxygenation and respiratory burst activity. o
Microbicidal mechanisms involve • Oxygen dependent damage eg H2O2 • Myeloperoxidase-halogen system with production of HCL03 and enhanced free chlorine.
Mφ Cyt Cont Macrophage mediated cytotoxicity involve ROI (H2O2 and superoxides, oxidant stress, potent against Obligate intracellular parasites in mφ (L.donovani and T. gondii); Plasmodium parasites in red blood cells (intraerythrocytic death); Mycobacterial (M.tuberclosis and M.Leprae) Staphylococcal (S.aureus) and salmonella (S.typhi) infection
NK Mediated Cytotoxicity (NK Cyt) Th1 cytokines (IL-2 and IFN-γ) activate NK cells Releasing pore-forming proteins (perforins), proteolytic enzymes (granzymes) and chemokines leading to apoptosis. NK provide early defence against Intracellular
infections (herpex group viruses, Leishmania and Listeria).
Primed
NK cells kill viral and tumour cells by apoptosis (low or no MHC Ag expression-target) ADCC mediated by killer (K) cells, a subpopulation of NK cells.
Delayed Type Hypersensitivity (DTH) Confer host protection against Bacteria
Mycobacterial infections (M.leprae; M.tuberclosis); o Chlamydia species; o Syphilis (Treponema pallidum infection) o Staphylococcal (S. aureus) and salmonella (S.typhi) infections; Obligate intracellular parasites (L.donovani, L. aethopica and T. gondii); Fungal infections ( mucocutaneous candidiasis and coccidiomycosis) o
DTH in Leshmaniasis Cutaneous leishmaniasis disease pattern. Allergic response in one extreme characterized hyperactivity to parasite antigens with few or no parasites (L.tropica) infection. Other extreme patients are anergic with multiple disseminated parasite filled ulcers and little spontaneous (L.aethiopia )infection. In between, an optimal DTH,a single sore leads to a spontaneous cure mediated by the DHT
DTH Leshmaniasis cont Protected individuals demonstrate Primed CD4+ T cells, activated macrophages, giant cells and absences of bacteria. Immunosuppressed patients have Increased replication of bacteria in macrophages Elevated CD8 T suppressor cells.
Parasite and Microbe Immune Evasion Stratagems Privileged
anatomical site Antigenic variation and camouflage/mimicry Impairment of phagocytic cell associated functions Latency infections and modulation of antigens.
Promotion of Epithelial Attachment Commensals
in epithelial surfaces (nasopharynx, colon) and pathogenic agents (Neisseria gonorrhoea) fail to induce protective sIgA Bacteria periodically changes pilin surface antigens.
Epithelial attachment cont Helicobacter
pylori survive in worst environment (pH -1.4) by converting urea into ammonia neutralizing acid and virus in salivary glands.
Disruption
of epithelial cells
o
Helicobacteria pylori secreted proteins or receptors used by
o
Streptococcus pneumoniae in the nasopharynx for transporting IgA and IgM antibodies
Intracellular Infection Intracellular infection facilitate avoiding antibodies eg Herpes
viruses, measles virus, mycobacteriae, brucellae, Cryptococcus neoformans, Plasmodium, leishmaniae, trypanosomes and toxoplasmas or spread directly from host cell to the other.
Physical Barriers Some parasites and microbes develop cell walls or physical barriers against immune attack. Encystment
strategy employed in E. granulosus, G. lamblia and E.histolytica infections. E. granulosus fibrous tissue surrounds fluid filled capsule containing protoscolices
Cell wall development T.spiralis
and T.saginata larvae surrounded by collagenous capsule in the muscles, providing a physical barrier. Mycobacteria elaborate lipid rich cell wall capsule resistant to lysosomal enzymes.
Intracellular Infections Malaria-infected erythrocytes express endothelial cell receptors facilitating adherence in the microvessels. Cerebral malaria uncommon in tolerant children Parasitized erythrocytes sequester evenly and thinly in various tissues Sporozoite in hepatocytes (liver anatomical arrangement) provide physical barrier o Prevent direct contact between hepatocytes and erythrocytes
Intracellular Infection cont Leishmania
proliferate and multiply without triggering phagocyte respiratory burst activity. Malaria uninfected red blood cells with high glutathione activity avoid the oxidant stress. o P.falciparum infected erythrocytes form spontaneous rosettes resistant to oxidative killing
Antigenic drift
A small change involving point mutation or single nucleotide alteration resulting in a single amino acid change recognized by the immune system In influenza virus point mutations in the genes coding for Haemagglutinin and Neuraminidase lead to many changes in its antigenic structure
Antigenic drift
Antigenic shift
Antigenic shift A
drastic change in antigenic structure that may be due to genetic reassortment between human and non-human viruses eg human and avian influenza A
Antigenic Variation Parasites in blood or interstitial fluid evade attack through antigenic variation through Periodic
alteration in membrane surface parasite epitopes Different variant surface glycoprotein expressed (VSG) by trypanosomes P. falciparum periodically alters
Antigenic var cont Changes in HIV envelope proteins through
Coding errors mediated by reverse transcriptase and High mutation rates during replication
Antigenic Variation cont Continuous change in the antigenic repertoire facilitates evasion of potent immune responses. Antigenic
variation displayed by bacteria (Neisseria gonorrhoea, intestinal bacteria). N. gonorrhoea possesses 50 distinct glycoprotein and lipopolysaccharide antigens and N. meningitidis expresses 10 antigenic types (serotypes). Rhinoviruses with 82 and enteroviruses with 62 different antigens.
Antigenic Variation cont Different antigens exists in protozoan infections Plasmodium
geographical subpopulations or variants responsible for antigenic variation in malaria. Classic antigenic variation displayed by trypanosome continuous change of variable surface glycoproteins (VSG)
Phagosome-Lysosome Fusion Prevention of phagosome-lysosome fusion allows Mycobacteria protected intracellular location (M. tuberculosis and Salmonella enterica) Bacteria release toxins and inhibitors, (subvert mφ and neutrophil mediated phagocytosis)
Phagosome-Lysosome Fusion cont Capsular components (N. meningitides and B. anthracis polysaccharides) antiphagocytic. S. aureus infections, sIgA mediates antiphagocytic activity through binding to IgG – Fc receptor sites o Diminishes Fc – R mediated opsonization and phagocytosis.
Phagocytosis Interference Parasites interfere with process of phagocytosis and the activation of oxidative killing mechanisms. T.gondii
parasites replicate in macrophages (inhibit phagosome – lysosome fusion) M. leprae and T. pallidum evolve cell walls resistant to lysosomal acid hydrolases and multiply in the cytoplasm.
Phagosome inteferance Chlamydia
enter directly into the cytoplasm and avoid phagosomelysosome fusion. Trypanosome cruzi rupture from the phagolysosomes, avoid low pH and high concentration of lysosomal hydrolases.
Phagocytosis Interference cont Plasmodium
parasites synthesize histidine rich proteins (HRP), o Potent
ROI inhibitors or scavengers
Bacterial
capsules serve as antiphagocytic shields (S. pneumoniae and S. aureus)
Inhibition of sIgA Protease Activity IgA protease and fabulation involve IgA 1 splitting at the hinge region results in Fab fragments that attach onto surfaces of organisms preventing binding of other antibodies (Neisseriae, Haemophilus influenzae). Gram-positive bacteria(Streptococcus pyogenes) secrete proteolytic enzymes which degrade Igs
Antigenic Mimicry/Camouflage Antigenic mimicry/camouflage involves incorporation of host proteins Schistosomes,
coated with ABO and HLA antigens (escape ADCC mediated by IgE) Larva stages of T.spiralis and E.granulosus acquire Igs on wall surfaces Viral influenza utilizes antigenic camouflage strategy
Molecular mimicry Parasite
genome encodes host- like gene sequences expressed on their surfaces (larval trematode stages).
Decoy Receptor – Mediated Endocytosis Intracellular pathogens employ receptormediated endocytosis to gain entry into the host cell through Expression of surface decoy ligand for receptor on target cell leading to binding and tricked engulfing of microbes EBV binds receptors on B cells, HIV attaches on CD4+ cells, T cells and mφs Influenza haemagglutinin binds carbohydrate expressed on target cell surfaces.
Receptor-mediated endocytosis Allows Bacteria (Salmonella typhi) to enter the host cell and M. tuberculosis binds C3 forming C3 convertase (opsonizes it for phagocytosis).
Avoidance of CD8+ CTL activity Dormancy or latency and inhibition of synthesis of class 1 MHC molecules eg HSV
synthesizes few proteins during dormancy CMV synthesizes proteins that degrade class 1 MHC molecules
Multiple Hosts Multiple
hosts- parasites complete life cycles by sequentially infecting one or more alternate hosts (P.vivax and S. mansoni). Parasites cause acute illness of short duration and finding other hosts (measles and influenza) o
Prevented through herd immunity leading to reduction in the number of susceptible targets to sustain an epidemic.
Multiple Hosts cont Chronic infection Evade immune response (malaria, trypanosomiasis, tuberculosis, leprosy and schistosomiasis) Commensalism Microorganisms
live harmlessly in the body (commensalism) or benefit the host (mutualism) thru o
Periodically changing surface antigens and coats itself with a polysaccharide capsule.
Antigenic Modulation/Capping Phenomenon
Capping by antibodies achieved when Combines
with microbial antigens, form complexes and move or Redistribute through the fluid medium of the host cell membrane to form a cap or cluster at one pole and Are either shed into the environment or endocytosed, hydrolysed in the lysosome (measles virus, T. gondii and leishmaniae)
Immunosuppression A profound or graded depression of immune responses. Involve
disruption of the lymphoid organ architecture (trypanosomes, HIV and CMV Direct damage of immunocytes (CMV)
Immunosuppression Result
in markedly decreased antibody responses, reactivation and multiplication of infectious agents. Impairment in specific antibody production -anergic leishmaniasis (L.aetropica)
infected patients. Chronic HBV infections, antibody responses markedly suppressed and poor In HIV infection profound decrease of CD4, CD8, and anti-viral factors occur o
Long Latency Period HIV and HBV associated with Long incubation periods without clinical expression of the disease. Quiescent or dormant period associated with absence of immune response and virus remains intact. Reactivation occurs during :Pregnancy o o o
Organ transplantation Blood transfusion Or infection induced immune system activation.
Vaccines
Vaccines Vaccination
and Immunization Vaccine Types Vaccine Production Most Widely Used Vaccines Expanded Program of Immunization
Vaccination and Immunisation Active
immunization-stimulation of immune system to develop its own immunity against pathogens Edward Jenner showed cowpox (L. vaccines) induced protection against smallpox o
Derived the concept of vaccination or immunoprophylaxis.
Passive
immunity conferred from administration of preformed antibodies (horse serum or human) o
Provide immediate protection of short duration.
Vaccination and Immunisation cont Active immunization involves the use of Live attenuated infectious agents; Detoxified killed bacterial extracts/secretions or products. In many viral infections like influenza, poliomyelitis, rabies, measles and mumps, both procedures widely applied. Unsuccessful immunization in neonates associated Poor polysaccharide antigens (bacterial capsule polysaccharides) Neonates commonly infected with encapsulated H. influenzae meningococci, pneumococci and group B streptococci, responsible for high
Types of Vaccines Inactivated vaccines killed organisms often with formaldehyde e.g., Prepared from killed entire organism (typhoid vaccine and inactivated polio vaccine (IPV). Attenuated vaccines: live organisms cultured to reduce pathogenicity, retain antigenicity eg BCG, measles, mumps and rubella and oral polio vaccine (OPV). Toxoids prepared from formaldehyde denatured diphtheria and tetanus bacteria toxins
Subunit vaccines Purified surface molecules of pathogens eg HBsAg expressed in E. coli Purified capsular polysaccharides of 23 strains for S. pnuemoniae vaccine.
Most Widely Used Vaccines Disease
Vaccine
Comments
Diphtheria
Toxoid
Tetanus
Toxoid
Often given to children in a single preparation (DTP; the “triple vaccine”) or the nowpreferred DTaP using acellular pertusis
Pertusis
Killed bacteria (“P”) or their purified components (acellular pertusis = “aP”)
Polio
Inactivated virus
Inactivated polio vaccine: IPV (Salk)
Attenuated virus
Oral polio vaccine: OPV (Sabin). vaccines trivalent (types 1,2 and 3)
Protein (HBsAg) from the surface of the virus
Made by recombinant DNA technology
Uses acellular pertusis and IPV (Salk)
Combination vaccine given in 3 doses to infants
Measles
Attenuated virus
Often given as a mixture (MMR). Do not increase the risk of autism.
Mumps
Attenuated virus
Rubella
Attenuated virus
Chicken pox (Varicella)
Attenuated virus
Caused by the variecella-zoster virus (VZV)
Influenza
Heamagglutinins
Contains heamagglutinins from the type A and type B viruses recently in circulation
Attenuated virus
Contains weakened viruses of the type B and two type A strains recently in circulation
Capsular polysaccharides
A mixture of the capsular polysaccharides of 23 common types. Works poorly in infants.
7 capsular polysaccharides conjugated to protein
Mobilizes helper T cells; works well in infants
Hepatitis B Diphtheria, hepatitis B
tetanus,
pertusis,
Pneumococcal infections
polio
and
Both
Live attenuated vaccine characte Possess
the advantages of being cheap; Administered orally; Confer long life protective immunity that mimics one acquired through natural infections. Multiply in the recipient and increase levels of the antigens and subsequent antibody dependent mechanisms. Single dose adequate for the induction of life long immunity.
Live vaccines characteristics Possess
the advantages of being cheap; Administered orally; Confer long life protective immunity that mimics one acquired through natural infections. Multiply in the recipient and increase levels of the antigens and subsequent antibody dependent mechanisms. Single dose adequate for the induction of life long immunity.
Inactivated or killed vaccines Require
multiple applications More stable and possess safety advantage if properly inactivated in comparison to live vaccines. Immunization coverage facilitated through availability of heat-stable, single dose, non-toxic and orally administered vaccines.
Toxoid vaccine production Toxin
produced from bacterial culture (C. diphtheriae and CI. tetanus vaccines) Diphtheria toxoid and tetanus toxoid formaldehyde-inactivated toxins adsorbed onto aluminium salts for increased immunogenicity. Toxoid tested for sterility, potency, innocuity; specific toxicity, adjuvant content, preservatives, content and identity.
Live Vaccines Production Viral vaccine production requires Use
of either living tissue (human, monkey and chicken embryos) or cell lines as substrates for viral growth.
Chicken
embryo used for yellow fever and influenza vaccines. Human cells employed in the production of o Rabies, measles, mumps, and rubella and polio vaccines. Attenuated BCG prepared from live culture filtrate of M.tuberculosis bovis
Expanded Programme of Immunization (EPI) Vaccines currently available include o Meningococcus, rotavirus, HAV, HBV, rabies, TB, o Measles, mumps, poliovirus, varicella zoster, o Tetanus, diphtheria, adenovirus, influenza, yellow fever, o Anthrax, cholera, plague, pneumococcus and typhoid. Global EPI include o Polio, measles, neonatal tetanus, pertussis (whooping cough), tuberculosis and hepatitis B (National immunization schedule for infants)
Schedule for Active Immunization of Children and Adults (Global EPI)
Age
Vaccine
Birth
Hepatitis B ( Hep B)
1-2 months
Hep B
2 months
Diphtheria and tetanus toxoids and cellular pertussis (DTP), Haemophilus influenzae type b ( Hib), inactivated polio (IPV) DTP, Hib, IPV, rotavirus ( RV).
4 months
Hep B, DTP, Hib, IPV, Rv
6 months
Oral polivirus vaccine (OPV), measles, mumps, rubella MMR,
12-15 months
Varicella vaccine for susceptible children
4-6 years
DTP, OPV, MMR
11-12 years
HepB, MMR, Varicella
25-64 years
Measles, rubella
>65 years
Influenza, meningitis and pneumonia
Kenya Expanded Programme of Immunization (KEPI)
Infant Age
Vaccine
At birth (or before 2 weeks) 6 weeks (1.5 months or soon after) 10 weeks (2.5 months or soon after) 14 weeks (3.5 months or soon after) 9 months or soon after
B.C.G., Oral Polio Oral Polio 1, + Pentavalent I Oral Polio II, + Pentavalent II Oral Polio III + Pentavalent III Measles, Yellow fever*
*Yellow fever vaccine is only available in Koibatek, Keiyo, Marakwet and Baringo Districts of Rift Valley Province. Pentavalent Vaccine = DPT + HBV + Haemophilus influenza type B (Hib)
Polio Vaccine Inactivated polio vaccine (IPV) and live attenuated trivalent oral polio vaccine (TOPV) Induce neutralizing IgG and sIgA antibodies effective against poliomyelitis. Major poliovirus protein antigen sites are VP1, VP2 and VP3. IPV (Salk vaccine) less efficient at inducing sIgA in the respiratory and intestinal tract systems Provides individual protection against polio paralysis. TOPV,Sabin (Type I, II, III) confers efficient gut humoral immunity but associated with risk of paralysis.
Polio Vaccine cont Combination
IPV and TOPV increases vaccine efficacy in poliomyelitis control programmes. Profound proteolytic environment of intestinal fluid alters the efficacy of live polio vaccines. TOPV preferred due Low cost Ease of administration Superiority in conferring intestinal immunity Extended vaccine coverage through infection of household and community contacts.
Meningitis Vaccine Vaccine
comprises 13 capsular polysaccharide antigens o Effective
against A and C serogroups.
Natural
meningococcal infections o Induce
protective anti-B group polysaccharide antibodies.
Measles Vaccine
Measles vaccine the last one to be given under the EPI schedule. Newly developed vaccine clinical trial -ISCOM (immune stimulated complex)
o Measles
virus proteins with purified plant extract (saponin)
DTP Vaccine Traditional DTP vaccine consists of three comp Detoxified tetanus toxoid; killed whole cell pertussis and C. diphtheriae bacteria. Acellular DTP vaccine contains either Filamentous haemagglutinin, pertactin and pertussis toxin inactivated with formalin and glutaraldehyde or One with filamentous haemagglutinin pertactin and genetically detoxified pertussis toxin. Acellular DTP vaccines are fairly safe, immunogenic and effective against pertussis.
Tuberculosis Vaccine Live attenuated Bacille Calmette-Guerin contains M. bovis. Vaccine only 50% - 80% effective against severe childhood TB meningitis and miliary TB. BCG vaccination does not lead to low-level infection No reliable immunological marker of protection against tuberculosis o Degree of protection not correlate with tuberculin test sensitivity
Hepatitis B Vaccine Plasma of symptomless carriers with hig(HBsAg) Inactivated through treatment with formaldehyde, heat, pepsin or urea. Recombinant DNA derived HBV vaccine Consist of hbsag particles expressed recombinant DNA in the yeast (immunogenic, effective and safe) Purified HbsAg particles adsorbed on aluminium hydroxide and preserved with thimmersol. HBV vaccine administered intramuscularly to the individuals at risk of infection
Yellow Fever Not
at the moment recommended for EPI.
Contains
freeze-dried live attenuated 17D virus strain. Highly immunogenic and confers protection for at least 10 years. Given to high-risk populations mainly in Rift Valley Province (Keiyo, Koibatek, Baringo and Marakwet).
Recombinant DNA vaccine Recombinant DNA technique involves Cloning of genes coding for putatively protective antigens Expression in and purification from prokaryotic cells like Escherichia coli.
Safer, immunogenic and free from side effects e.g. Recombinant vaccinia virus vaccines produced by introducing foreign viral DNA into the vaccinia DNA Hepatitis B, herpes simplex, rabies, and other viral vaccines
Major advantages of these vaccines
Low cost and ease of administration by multiple pressures or by scratch technique
Synthetic Vaccines Chemical synthesis of antigen involves
Encoding by isolated genes, Sequenced and putative peptides assembled eg
Wholly synthetic vaccines explored for malaria and diarrhoel diseases, o New conjugate vaccine for Haemophilus influenza type B, Hib. o
Idiotypic Vaccines Idiotypic
vaccines involve use of anti -idiotype antibodies o Serves as a mock antigen including antibodies that recognize and block the original antigen (idiotype). Elicit non-MHC restricted specific cellular immunity Used as alternatives to polysaccharide derived vaccines (normally poor immunogens for antibody responses)
Internal image vaccines Major advantages Overcome
constraints in vaccination against some parasites and viruses due to their antigenic variation strategen to avoid immune attack. Circumvent HLA restricted T cell reactive vaccines (epitopes)
Subunit Vaccines Purified surface molecules are subunits of pathogens eg
HBsAg expressed in E. coli Purified capsular polysaccharides of 23 strains for S. pnuemoniae vaccine.