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.