ANTIBODY-DEPENDENT IMMUNE RESPONSE

DR.P.K.CHEBOSS

DEPARTMENT OF IMMUNOLOGY
MOI UNIVERSITY SCHOOL OF MEDICINE

6.6.2016 1
 Origin of B cells

10-Mar-08 EHS 210 2

 ANTIBODY-DEPENDENT RESPONSES
B Cell Development
• In the germ line of pluripotent stem cells, constant
region (C), diversity (D), joining (J) and variable
(V) region Ig genes are encoded.
• Heavy (H) chain gene elements are VH, D and JH
while VL and JL are for light chains of an Ig.
• Genes for Ig kappa () and lambda () are on
chromosome 2 and 22, respectively.
• Gene segments for CH are arranged linearly in the
order Cμ, Cδ, Cγ3, Cγ1, pseudogene Cε, Cα1,
Cγ2, Cγ4, Cε and Cα2.  
• Somatic recombination occurs before contact with
antigen exposure during B cell development in the bone
marrow.
• One D and one J rearrange with DJ segment and
similarly one V and J rearrange with VJ.
– :V(D) J recombination is expressed in developing B cells and
recognize recombination signal sequences.
• This reguires recombination activating genes 1 and 2(RAG-1
and RAG-2) expressed on developing lymphocytes.
• The initial event in recombination is the recognition of 12bp
spacer RSS by RAG1 then RAG2 associate with RAG-1 and
the heptamer forming a synaptic complex.
:undergo D-J joining on H-chain to become early pro-B cells and
express CD45 (B220) and class II MHC molecules.
 TABLE 10: Stages in B Cell Development
 

  Stem Early Late Large Small Immat Mature

cell pro-B pro-B pre-B pre-B ure B B cell
cell cell cell cell cell

H Germ D-J V-DJ VDJ VDJ VDJ VDJ

chain line joining joining rearran rearran rearran rearran
genes ged ged ged ged

L Germ Germ Germ Germ V-J VJ VJ

chain line line line line joining rearran rearran
genes ged ged

Surfac none none none µ chain µ chain Membr Membr

e Ig in pre- in ane ane
B cytopla IgM IgM
recepto sm and and
r on IgD
surface
• Each B cell generates a set of functional antibody
genes such that there is one VDJ gene for the
heavy chain and one VJ gene for either kappa ()
or lambda () of light chain.
• Transcription of these genes permits formation of
antibody molecules with a single combining
specificity able to interact with antigenic
determinant in a very specific manner through
BCR.
• Variable domains contain three hypervariable
(complementarity determining regions, CDRs)
comprising N-terminal domains of both heavy and
light chains.
. 
Antigenic Receptors 
• Antigenic receptors are immunoglobulin (Ig) gene
superfamily molecules consisting of mainly BCR, TCR,
MHC class I and II, 2-microglobulin, CD2, CD3, CD4,
CD8 and C-reactive proteins.
:all these molecules are considered antigen specific
receptors and members of the supergene family with
Ig- like domains.
• Ig molecules possess a single combining site specificity
that interacts with antigenic determinants in a specific
manner via BCR.
• Membrane Ig (SmIg) comprises IgM and
IgD co-expressed on surface of naïve virgin
mature B cells.
:antigenic specific receptors are mainly
expressed on B cells (BCR) and T cells (TCR).
– Variable domains contain three hypervariable
(complementarity determining region, CDR)
and constant heavy region responsible for
biological functions of the Ig.
Immunoglobulin Diversity
• The body is capable of recognizing over 1016
different antigens through:
: multiple genes in the germ line DNA,
:variable recombination and various mutations
during differentiation of germ line cells into B
cells.
:expression of germ line multiple variable (V)
region genes;
:VJ and VDJ combinations,
:random assortment of H and L chains;
:imprecise DNA recombination;
:various mutations which may occur in the V
genes of H or L chains in the life time of a B cell
:receptor editing.
 Homework.
• Allelic exclusion.
• Regulation of B cell development.
• Clonal selection theory.
• Clonal abortion.
• Clonal anergy/silencing.
• Immunologic tolerance.
B Cell Activation
• Antigen specific signals are derived from
interaction between B cells (APCs) and T
cells that provide cytokines (T cell
dependent activation) leading to production
of specific antibodies.
• In non-specific B cell activation, there is no
involvement of T cells and polyclonal
antibodies are produced.
• There are also natural antibodies which
arise independently of any known antigenic
stimulation and can react with exogenous
antigens.
Antigen specific B cell activation-T cell
dependent.
• Require processing and presentation of
antigen in an immunogenic form by the
accessory APCs.
:B cells appear to ingest only soluble antigens
by the process of pinocytosis.
:antigenic determinants generated are re-
expressed on the surface of B cells in
association with class II MHC antigens.
• This leads to the activation of CD4 T cells
liberating several interleukins (IL-4 and IL–
 ;IL-4 stimulates B cell proliferation and
mediates IgM+ B cell switching to IgG and
other 1g classes as well as development of Fc-
receptors on B cells.
:IL – 5 induces B cell proliferation and
differentiation into IgM secreting cells.
  
Fig.
  13: T cell Dependent Activation of B cells. Endocytosis of antigen
 
digestion and interaction with MHC molecules and CD4 T cells leads to
differentiation of B cells into plasma cells that secrete antibodies. Refer to text
for details. Source: users.rcn.com/ikimball.ma.ultranet/BiologyPages/B/B_and
T-cells.html
 
Non-specific B cell activation
.Polyclonal activation occurs due to
:B cell expression of membrane receptors for C3d and
Epstein-Barr virus (EBV);
:protein A – bearing staphylococci and gram-
negative bacterial lipolysaccharides.
:mitogens such as plant lectins (phytohaemagglutinin,
pokeweed mitogen);
:anti-Igs; antibodies to certain B cell differentiation
antigens;
:bacterial and parasite derived products; tumour
promoting agents.
• Levels of immunoglobulins produced through both antigen-specific
and non-specific activation of B cells depend on the
:ethnic background, age and sex;
:history of allergy;
:recurrent infections or endemicity of parasites in a particular
population.
Kinetics of Primary and Secondary Responses
• Primary response is characterized by
:first measurable immune response,
:a longer lag phase and
:IgM predominant antibody.
• Secondary response is associated with
:a second exposure to same antigen,
:shorter lag phase,
:quicker onset and a higher magnitude,
:long lived memory and anamnestic response :IgG as the
predominant antibody.
  

Fig. (Image) 14. Kinetics of Primary (10) and Secondary (20) Immune Responses: Initial administration of antigen at day O leads to a
lag phase before IgM antibodies are generated 10-14 days post-immunization period. When the antigen is again given at 28 days, as a
booster, the immune response detected is more pronounced and durable and the lag period is shorter. Primary response is characterized by
IgM antibody production while a secondary response is predominantly of IgG and other classes later Source:
www.gla.ac.uk/-jmb17n/Teaching/L2taching/memvacc/pictures/secab.jpg.
• The basic formula of Ig submits is
:H2 L2, a four chain structure (some Igs composed
of polymers of the basic monomeric form).
• Five different kinds of C regions for H chains
define isotypes (classes)
: mu (u) chains (H chain of IgM);
:gamma () chains (IgG);
:alpha () chains (IgA);
:delta () chains (IgD), and epsilon () chains
(IgE).
• Light chain is composed of 220 amino acid
residues
• Heavy chains composed of 440-550 amino acids
held together by covalent disulfide bonds.
• Variable regions are contained within the (NH2)
Regulatory structures on the V and C regions
• Ig determinants on V and C regions are
continuously generated and execute self-
regulation of Ig synthesis and production.
: isotypes expressed by C region
: allotypes expressed by both constant and variable
regions;
: idiotypes expressed by V region of heavy and
light chains.
• Paratopes
IgG Molecule
• IgG molecule exists as a monomer in membrane-
bound form on the surface of B-lymphocytes and
in secreted form.
• About 150 kDa in Mw .

• consist of 4 sub-classes: IgG1, gG2, IgG3, and

IgG4.

• It is the only Ig able to cross the placenta (adult

maternal antibody) to protect infant.
• IgG is produced by plasma cells in secondary
lymphoid organs (lymph nodes and spleen) and
constitutes about 70 – 75% of total
immunoglobulins produced daily in the body.
.The structure of an IgG displays a basic structure of
an Ig consisting of four polypeptides
: two light (L) chains (Mw 25kDa) and two heavy
(H) chains (Mw 55 – 77kDa).
• Held together by inter-and intra-chain
disulphide (S-S) bonds.
• Each chain is divided into variable (V) antigen
binding fragment (Fab) and a constant (C) or
crystallizable fragment (Fc).
 IgG subclasses
• IgG subclasses consist of four polypeptides: γ1, γ2,
γ3 and γ4, designated IgG1, IgG2, IgG3 and IgG4,
respectively.

• Their average normal serum concentrations are 60

– 70% (IgG1); 14 – 20% (IgG2); 4 – 8% (IgG3); 2
– 6% (IgG4) of normal IgG levels.

• Distribution of the IgG subclasses is based on the

number and arrangement of inter-heavy chain
disulphide bonds.
.
 :IgG associated biological properties differ at the
subclass level.
: complement activation is in the order of IgG3 >
IgG1 > IgG2 > IgG4.
:Transmission across the placenta of IgG molecules
occurs at relatively the same rate with IgG1, IgG3
and IgG4 while IgG2 transmission is either minimal
or non-existent.
• Functions of IgG:
-potent anti-toxin.
-opsonization.  
-Complement actvation.
 IgM molecule
• IgM molecule exists as a monomer on surface of
B cells.
• It exists as a receptor pentamer with Mw of about
970 kDa.
• each monomer about 180 kDa.
• Has ten antigen-binding sites.
: Monomers are joined together through disulphide
bridges.
• J-chain about 15 kDa.
• IgM is produced in the lymph nodes and spleen
and represents about 10% total serum Ig produced
during the primary immune response.
• IgM rises rapidly (3-4 weeks) of life then gradually
decreases.
• adult levels achieved at 2 years and intrauterine
infection in infants leads to increased IgM levels
and sometimes IgA
• Circulating IgM molecule is a pentamer of five
four-chain polypeptides held together by
disulphide linkages and J-chain polypeptides.
• Functions of IgM:
-Agglutination.
-efficient complement system activation.
Serum IgA
• Serum IgA exists as a monomer of about 160 kDa
Mw (80%) or dimmer of about 415 kDa (20%)
held together by J-chain (15 kDa).
 Secretory IgA (sIgA)
• sIgA exists primarily as a dimer of Mw 390 kDa
held together.
• Has J-chain (15 kDa ).
• Has secretory component, extra polypeptide of
about 70 kDa in Mw.
: secretory component is synthesized by mucosal
epithelial cells and delivered from the poly – Ig-
receptor.
• IgA is then released as secretory IgA (sIgA) in the
lumen of mucosa.
• the secretory piece is covalently linked to Fc of
IgA and wrapped around the Fc-portion of the IgA
dimmer.
Synthesis and functions of sIgA
• Primed T cells regulate IgA committed B cells and
the production of IgA immunoglobulins.
• Peyer’s patches consist of cuboidal epithelium
cells, unique antigen presenting cells called M
cells, which are actively pinocytic.
• They take up the antigen and deliver it to
underlying mucosal lymphoid tissue.
• T cells are sensitized and precursor IgA committed
B cells are stimulated, leave the Peyer’s patches
and migrate into mucosal tissue and secretory
glands.
• B cells then differentiate into plasma cells, which
secrete IgA immunoglobulins specific for the
antigen first encountered in the mucosal associated
lymphoid tissue (MALT).
• A dimeric form is produced in external secretions
such as saliva, acromial, bronchial and genital
tract secretions.
FUCTIONS OF sIgA  
1. Protection in the sub-epithelial mucosal areas
such as upper respiratory, urogenital and
gastrointestinal tracts.
2. plays a major role in preventing antigen uptake
derived from both infectious and non-infectious
agents.
3 sIgA provides protection against infections,
allergic reactions (immediate type) and autoimmune
diseases.
4 Exclusion of bacterial and viral pathogens,
bacterial toxins and other noxious agents.
5 Clears infections through transport of pathogen
immune-IgA complexes into the bile.
6 potentiates mucous viscosity in the blocking and
removal of infectious agents.
7 mediates antibody-dependent T cell – mediated
cytotoxicity (ADCC) .
8 Interferes with utilization of growth factors like
iron by bacterial pathogens.
 9 increases antigen uptake by M cells into Peyer’s
patches.
10 lymphocyte activation through anti-idiotypic
antibody stimulation.
 IgE molecule
• IgE is a reagenic or homocytotropic Ig responsible
for Type I hypersensitivity reaction.
• It exist as monomer of Mw 188 kDa .
• bout 0.001%, the lowest concentrated fraction of
all Igs in serum.
• IgE mediates ADCC through binding to Fc-R on
eosinophils against helminths.
.

IgD molecule
• IgD molecule exists as a monomer on B-
lymphocytes where it functions as BCR and both
IgM and IgD on mature B cells have identical
antigen binding specificity.
• The monomer is of Mw 185 kDa with 14%
carbohydrate.
• constitutes only 1% of circulating antibodies.
• The structure of IgD corresponds to a standard Ig
with a very long hinge region of about 64 amono
acid residues. Secreted IgD is extremely labile,
present in very low levels in serum without any
known effector function.
• It appears to play an important role in the
initiation of a primary antibody response.
Vaccines

• Edward Jenner showed that inoculation with

cowpox (L. vaccines of cows) induced protection
against smallpox (highly contagious and fatal
disease) thereby deriving the concept of
vaccination or immunoprophlaxis.
• Active immunization refers to stimulation of
immune system to develop its own immunity
against pathogens
• passive Immunizaion-Administration of
preformed antibodies (horse serum or human)
which provide immediate protection of short
duration.
• Immunoresistance is developed through

:natural, clinical, latent or sub-clinical infections.

• Immunopotentiation may be achieved by

sustained release of antigens through
:a depot effect such as that of aluminium salt
adjuvants,
:delivery of antigen directly to APCs such as m or
continuous exposure to antigen as it occurs in
chronic infections.
.
• 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 are widely applied.
 Types of vaccines
• Killed whole organisms often with
formaldehyde (inactivated organisms) are
:vaccines prepared from killed entire organism
such as typhoid vaccine and inactivated polio
vaccine (IPV).
• Attenuated organisms are cultured to reduce
pathogenicity and still retain antigenicity and
include:
:Bacillus Calmette-Guerin (BCG), measles, mumps
and rubella and oral polio vaccine (OPV).
• Toxoids are prepared from diphtheria and tetanus
bacteria grown and liberated protein toxin is
 

Recombinant DNA vaccine

• Recombinant DNA technique involves the cloning
of genes coding for putatively protective antigens
and their expression in and purification from
prokaryotic cells cells like Escherichia coli.
:are safer, immunogenic and free from side effects
such as
:recombinant vaccinia virus vaccines produced by
introducing foreign viral DNA into the vaccinia
DNA as in the generation of hepatitis B, herpes
simplex, rabies, and other viral vaccines
both live and subunit vaccines are being developed
against parainfluenza (PIV) and RSV infections.
• Major advantages of these vaccines include
: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 as in
wholly synthetic vaccines explored for malaria
and diarrhoel diseases,
:new conjugate vaccine for Haemophilus influenza
type B, Hib.
 Idiotypic vaccines
• Idiotypic vaccines involve use of anti -idiotype
antibodies where the original antibody (idiotype)
provokes an antibody (anti-idiotype) that does not
cause disease but serves as a mock antigen
including antibodies that recognize and block the
original antigen (idiotype).
• They elicit non-MHC restricted specific cellular
immunity and are also used as alternatives to
polysaccharide derived vaccines which are
normally poor immunogens for antibody
responses.
• internal image vaccines are of major advantage in
overcoming constraints in vaccination against
some parasites and viruses due to their antigenic
variation devised as a strategen to avoid immune
attack.
 Paraspecific vaccines
• Paraspecific vaccines are effective in combating
viral infections particularly
:herpes, hepatitis B and C infections,
:chronic inflammatory diseases and also as an
adjuvant therapy for tumours.
 TABLE 13: Most Widely Used Vaccines

Disease Vaccine Comments

Diphtheria Toxoid Often given to children in a single

preparation (DTP; the “triple vaccine”) or the
Tetanus Toxoid now-preferred 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). 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 Uses acellular pertusis and IPV (Salk) Combination vaccine given in 3 doses to
hepatitis B 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 Mobilizes helper T cells; works well in

protein infants
Staphylococcal infections 2 capsular polysaccharides conjugated to To prevent infection by Staph. Aureus in
protein patients hospitalized and/or receiving
dialysis.
Meningococcal disease 4 polysaccharides conjugated to protein To prevent new outbreaks

Hemophilus influenzae, type B (Hib) Capsular polysaccharide conjugated to Prevents ear infections in children
protein

Hepatitis A Inactivated virus Available in single shots with HBsAg

Rabies Inactivated virus Vaccine prepared from human diploid cell

cultures (HDCV) has replaced the duck
vaccine (DEV)
Small pox Attenuated virus Global eradication of small pox

Anthrax Extracted of attenuated bacteria Primarily for veterinarians and military

personnel

Typhoid Three available:  

1 Killed bacteria
2 Live, attenuated bacteria (oral)
3 Polysaccharide conjugated to protein
Yellow fever Attenuated virus Given to travelers

Tuberculosis Attenuated bacteria (BCG)  

Viral Hepatitis Hepatitis B Susceptible health – care personnel,

homosexual males, intravenous drug users

Rabies Disease Rabies Veterinarians, animal handlers, and animal

bite victims.

  Meningococcus, yellow fever, cholera, Travelers to certain areas.

typhoid fever, plague, Japanese B
encephalitis, polio
• Generally live vaccines
:possess the advantages of being cheap;
:can be administered orally;
:and confer long life protective immunity that mimics one
acquired through natural infections.
:they multiply to a certain degree in the recipient and
increase levels of the antigens and subsequent antibody
dependent mechanisms.
:a single dose is usually adequate for the induction of life
long immunity.
. Inactivated or killed vaccines require multiple applications
to produce comparable optimum antibody levels.
: they are more stable and appear to possess safety advantage
if properly inactivated in comparison to live vaccines.
• Immunization coverage would be facilitated through the
availability of heat-stable, single dose, non-toxic and orally
administered vaccines.
 General Vaccine Production 
Toxoid vaccines
•  Toxin is produced from bacterial culture such as in the
generation of C. diphtheriae and CI. tetanus vaccines.
• Both diphtheria toxoid and tetanus toxoid are
formaldehyde-inactivated toxins adsorbed onto aluminium
salts for increased immunogenicity.
• The toxoid is then tested, as for all vaccines, for sterility,
potency, innocuity; specific toxicity, adjuvant content,
preservatives, content and identity.
Live vaccines
• Viral vaccine production requires use of either living tissue
(human, monkey and chicken embryos) or cell lines as
substrates for viral growth.
 Expanded Programme of Immunization (EPI)
• Vaccines currently available include meningococcus,
rotavirus, HAV, HBV, rabies, TB, measles, mumps,
poliovirus, varicella zoster, tetanus, diphtheria,
adenovirus, influenza, yellow fever, anthrax, cholera,
plague, pneumococcus and typhoid.

• Those used in the global EPI include polio, measles,

neonatal tetanus, pertussis (whooping cough),
tuberculosis and hepatitis B as shown in Table 14 A

• The national immunization schedule for infants

recommended by WHO EPI and employed by Kenya
Expanded Programme of Immunization (KEPI) is
shown in Table 14 B
TABLE 14A: 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

 TABLE 14 B: Kenya Expanded Programme of Immunization (KEPI)
 
Infant Age Vaccine

At birth (or before 2 weeks) B.C.G., Oral Polio

6 weeks (1.5 months or soon after) Oral Polio 1, + Pentavalent I
10 weeks (2.5 months or soon after) Oral Polio II, + Pentavalent II
14 weeks (3.5 months or soon after) Oral Polio III + Pentavalent III
9 months or soon after 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
 Inactivated polio vaccine (IPV) and live attenuated
trivalent oral polio vaccine (TOPV) both induce
neutralizing IgG and sIgA antibodies effective
against poliomyelitis.
• Major poliovirus protein antigen sites are VP1,
VP2 and VP3.
• IPV (Salk vaccine) is less efficient at inducing
sIgA in the respiratory and intestinal tract systems
: provides individual protection against polio
paralysis.
• TOPV (Sabin) is an attenuated trivalent vaccine
(Type I, II, III) that confers an efficient gut
humoral immunity and is associated with risk of
paralysis.
• A combination of both IPV and TOPV could
increase the vaccine efficacy in poliomyelitis
control programmes.
• Generally, profound proteolytic environment of
intestinal fluid alters the efficacy of live polio
vaccines.
• TOPV is preferred because of
:its low cost,
:ease of administration,
:superiority in conferring intestinal immunity
:extended vaccine coverage through infection of
household and community contacts.
 Meningitis vaccine
• The vaccine comprises about 13 capsular
polysaccharide antigens effective against A and C
• Natural meningococcal infections lead to
production of protective anti-B group
polysaccharide antibodies.
 Measles vaccine
•  Measles vaccine is the last one to be given under
the EPI schedule.
• Newly developed vaccine under clinical trials
include ISCOM (immune stimulated complex)
that combines measles virus proteins and purified
plant extract saponin which boosts immune
responses to the measles antigens;
• ALVAC is an attenuated carnorypox virus used as
a vector for a DNA-derived measles vaccine a
combination between a gene encoding measles
virus N-protein and BCG vaccine
 DTP vaccine
• Traditional DTP vaccine consists of three
components; detoxified tetanus toxoid; killed
whole cell pertussis and Corynebacterium
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.
• The two acellular DTP vaccines are fairly safe,
immunogenic and effective against pertussis.
 Tuberculosis vaccine
• A live attenuated Bacille Calmette-Guerin
containing M. bovis.
: vaccine only 50% - 80% effective against severe
childhood TB meningitis and miliary TB.
• BCG vaccination does not lead to low-level
infection that would induce and maintain
protective immunity against TB.
• No reliable immunological marker of protection
against tuberculosis, as the degree of protection
does not correlate with degree of tuberculin test
sensitivity.
Hepatitis B vaccine
• Originally derived from pooled human plasma of
symptomless carriers with high titers of purified
hepatitis b virus surface antigen (HBsAg).
:inactivated through treatment with formaldehyde,
heat, pepsin or urea.
• Recombinant DNA derived HBV vaccine
consisting of HBs Ag particles expressed
recombinant DNA in the yeast is currently
preferred and found to be substantially
immunogenic, effective and safe.
• The recombinant products of HBV vaccine are
made up of
:purified HBs Ag particles adsorbed on aluminium
hydroxide and preserved with thimmersol.
• HBV vaccine is administered intramuscularly to
the individuals at risk of infection including:  
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).
  Immunization Associated Complications
Immature age
• Young infants and newborns may not respond
vigorously as they could be immunologically
immature.  
Toxicity
• Vaccines such as gram – negative derived typhoid
endotoxins and other microbial contaminations
induce pyrogenic reactions.
• Cholera toxoid has also a tendency for partial
reversion to toxicity.
 Infections
• Live attenuated vaccines may revert to virulent
strains.
• Paralysis is associated with TOPV (vaccine
associated paralysis) and adenilitis with BCG
vaccination.
 Potentiation of atypical disease
• Administration of inactivated vaccines against
paramyxoviridae, Respiratory syncytical virus
(RSV) and measles virus can result in the
potentiation of atypical disease after subsequent
natural infection.  
Decreased vaccine immunogenicity
• Inactivation with formaldehyde treatment alters
surface glycoproteins of virus leading to decreased
immunogenicity such as F glycoproteins of
measles virus and G glycoproteins of RSV
vaccine.
• Hypersensitivity Reactions.