infection and immunity
TRANSCRIPT
INFECTION AND IMMUNITY
Major Areas
Definitions of ImmunityAntibody dependent protective
mechanismsComplement mediated protectionCell mediated protective
mechanismsParasite 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).
Sterile Immunity State of protection when all the
infectious agents are eliminated in the host.
PremunitionLow-grade infection providing
protection in subsequent asymptomatic chronic infections
Occurs in several infections, malaria and diphtheria (Corynebacterium diphtheria).
Immunity Profile
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
Immunity Profile cont
Innate Determinants of ImmunityGenetic DeterminantsPhysical BarriersSoluble FactorsCellular Components
Innate immune responses involve Genetics, anatomical barriers,
bacterial antagonismsPattern-recognition receptors (PRR)Soluble factorsNonspecific defense chemicals,
complement proteins
Innate Mediated Factors
Cellular (cells) components Neutrophils, monocytes and
macrophages Basophils, mast cells and eosinophils
release inflammatory mediators.
Alternative pathway of complement activation
Provides defense against gram-negative bacteria
Interferons inhibit viral replication and activate inflammatory cells.
Innate Mediated Factors cont
Innate protection associated withNegative Duffy (a-b) blood groups
(Plasmodium vivax); Sickle cell trait A/S and glucose-6-
phosphate (G-6-PO4) dehydrogenase
deficiency. Plasmodium infected erythrocytes highly
susceptible to toxic oxygen intermediates or radicals.
Intracellular development of P.falciparum in G-6-PO4 dehydrogenase deficient erythrocytes is inhibited or retarded.
Genetic determinants of malaria immunity
Physical Barriers To Infection
Barrier site (first line of defense)
Activity
Skin sweat Flushing, organic acids
Skin and GI tract natural fauna
Compete for niches
GI tract Peristalsis, low pH, bile acid, flushing, antibacterial peptides Lung tracheal cilia Mucociliary elevation
Nasopharynx, mucus and saliva, eye tears
Flushing, lysozymes
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.
Antimicrobial Peptides
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.Source; http://www.whfreeman.com/COH1/phagocytosis.htm
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
Microbicidal Mechanisms
Macrophage Derived Factors and ActivitiesProducts Activity
Metabolites:Reactive oxygen intermediates (ROI)Reactive nitrogen intermediates (RNI)Eicosanoids, prostaglandins leukotrienesPlatelet activating factor
Inflammation and intracellular killingInflammation and intracellular killingRegulation, inflammationRecruitment and activation of platelets.
Cytokines:IL-1, TNF-, IL-6IFN-IL-10IL-12, IL-18TGF- β
InflammationTh1 activationTh1 suppression, Th2 activationActivation of NK and T cellsInflammation, tissue repair
Adhesion molecules:FibronectinThrombospondin
OpsonisationAdhesion, phagocytosis
Complement:C3b, C4b and C2b Opsonisation
Enzymes:LysozymeCollagenase, elactase
Degrades bacterial cell wallsMatrix 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 of o Filarial worms (microfilariae), o Tapeworms (protoscolices of E. granulosus)
ando Amastigotes of leishmania parasites.
Antibody Dependent Mechanisms
Inhibition of epithelial attachment
Neutralization activityFc-R mediated opsonization and
phagocytosisFc-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.
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);
salmonellosis (Salmonella typhi)
Inhibition of Epithelial Cell Attachment
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 neuraminidase receptor sites.
Neutralizing Antibody Activity cont
Mechanism effective against various pathogenso 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.
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)
Neutralizing Antibody Activity cont
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);
Ab Mediated Opsonization and Phagocytosis
Opsonization and phagocytosis
Protozoan infectionso Malaria (P.falciparum), o Trypanosomiasis (T.rhodesiense);
Echinococcosis (E.granulosus protoscolices);
Viral infections (HBV).
Target organism or parasite killing due to released cytotoxic factorso Perforins,o Lymphotoxins and o Neutral serine proteases)
Eosinophil derived cytotoxic peroxidase (EPO), eosinophil cationic protein (ECP) and major basic protein (MBP) mediate killing
ADCC effective against helminthic infectionso Schistosomulae (S. mansoni and S. haematobium) o Microfilariae (W.bancrofti and Onchocerca volvulus)
during natural oncocerciasis infections
Antibody Dependent Cell Mediated Cytotoxicity (ADCC)
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
cytotoxicityNK cell cytotoxicityDelayed type hypersensitivity
(DTH)
Cytotoxic T Cells (CTL)
CTL mediate antigen – specific, class 1MHC – restricted cytotoxicity against o 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 Viral and protozoan infections (influenza and
malaria) o Influenza virus infected cells lysed by CTL.
CTL ContDisease progression correlates with T cell
responses and IgM-anti-HCV antibodies.Intracellular development of parasites P. falciparum inhibited by CTL andCytokines (TNF, IL-6 and C-reactive
proteins) Sporozoites induce CTL that
o Recognize plasmodium parasite antigens on the surface of malaria infected hepatocytes
o Damaged by the parasite specific CD8+ CTL.
Macrophage Mediated Cytotoxicity
CTL derived -IFN efficiently activate m to fuse their phagosomes and lysosomes more o Increase synthesis of NO, ROI, antimicrobial
peptides and IL-12.
Activated m 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 m
(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
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 sub-
population of NK cells.
NK Mediated Cytotoxicity (NK Cyt)
Confer host protection against
Bacteria o 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)
Delayed Type Hypersensitivity (DTH)
DTH in LeshmaniasisCutaneous 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.
Privileged anatomical siteAntigenic variation and
camouflage/mimicryImpairment of phagocytic cell
associated functionsLatency infections and modulation of
antigens.
Parasite and Microbe Immune Evasion Stratagems
Commensals in epithelial surfaces (nasopharynx, colon) and pathogenic agents (Neisseria gonorrhoea) fail to induce protective sIgA
Bacteria periodically changes pilin surface antigens.
Promotion of Epithelial Attachment
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 cellso Helicobacteria pylori secreted proteins
or receptors used byo Streptococcus pneumoniae in the
nasopharynx for transporting IgA and IgM antibodies
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.
Intracellular Infection
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
Physical Barriers
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.
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 barriero Prevent direct contact between hepatocytes
and erythrocytes
Intracellular Infections
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
Intracellular Infection cont
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 VariationParasites 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 RBC surface proteins to avoid recognition.
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 m and neutrophil mediated phagocytosis)
Capsular components (N. meningitides and B. anthracis polysaccharides) anti-phagocytic.
S. aureus infections, sIgA mediates anti-phagocytic activity through binding to IgG – Fc receptor sites o Diminishes Fc – R mediated
opsonization and phagocytosis.
Phagosome-Lysosome Fusion cont
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 phagosome-lysosome 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
scavengersBacterial capsules serve as anti-
phagocytic 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 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
Antigenic Mimicry/Camouflage
Molecular mimicry
Parasite genome encodes host- like gene sequences expressed on their surfaces (larval trematode stages).
Decoy Receptor – Mediated Endocytosis
Intracellular pathogens employ receptor-mediated 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 ms
Influenza haemagglutinin binds carbohydrate expressed on target cell surfaces.
Receptor-mediated endocytosis
Allows Bacteria (Salmonella typhi) to enter the
host cell andM. tuberculosis binds C3 forming C3
convertase (opsonizes it for phagocytosis).
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
Avoidance of CD8+ CTL activity
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
Chronic infectionEvade immune response (malaria,
trypanosomiasis, tuberculosis, leprosy and schistosomiasis)
CommensalismMicroorganisms live harmlessly in the
body (commensalism) or benefit the host (mutualism) thruo Periodically changing surface antigens and
coats itself with a polysaccharide capsule.
Multiple Hosts cont
Capping by antibodies achieved whenCombines 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)
Antigenic Modulation/Capping Phenomenon
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
Immunosuppression
Result in markedly decreased antibody responses, reactivation and multiplication of infectious agents.
Impairment in specific antibody production -anergic leishmaniasis (L.aetropica) infected patients. o Chronic HBV infections, antibody
responses markedly suppressed and poor In HIV infection profound decrease of CD4,
CD8, and anti-viral factors occur
Long Latency Period
HIV and HBV associated withLong 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 :Pregnancyo Organ transplantationo Blood transfusiono Or infection induced immune system
activation.
Vaccines
Vaccines
Vaccination and ImmunizationVaccine TypesVaccine ProductionMost Widely Used VaccinesExpanded 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 smallpoxo 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 mortality in the young.
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
Types of Vaccines
Subunit vaccines
Purified surface molecules of pathogens egHBsAg expressed in E. coli Purified capsular polysaccharides of 23
strains for S. pnuemoniae vaccine.
Most Widely Used Vaccines
Disease Vaccine Comments
Diphtheria Toxoid Often given to children in a single preparation (DTP; the “triple vaccine”) or the now-preferred DTaP using acellular pertusisTetanus Toxoid
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). Both vaccines trivalent (types 1,2 and 3)
Hepatitis B Protein (HBsAg) from the surface of the virus Made by recombinant DNA technology
Diphtheria, tetanus, pertusis, polio and hepatitis B
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
Pneumococcal infections 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
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 productionToxin 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)
o Recommended by WHO EPI and employed by eg KEPI
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 PolioOral Polio 1, + Pentavalent IOral Polio II, + Pentavalent IIOral Polio III + Pentavalent IIIMeasles, 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 VaccineInactivated 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
infectionso 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 vaccineRecombinant 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
vaccinesMajor advantages of these vaccines Low cost and ease of administration by multiple
pressures or by scratch technique Vaccine stability and long shelf life with potential use
of polyvalent (mixed) antigens.
Synthetic Vaccines
Chemical synthesis of antigen involves Encoding by isolated genes, Sequenced and putative peptides
assembled ego Wholly synthetic vaccines explored for
malaria and diarrhoel diseases, o New conjugate vaccine for
Haemophilus influenza type B, Hib.
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.