Killed and subunit vaccines

1. Killed And Subunit
Vaccines
Dr. Harmeetpal Singh

2. Vaccine
Vaccine is an immunobiological preparation that provides specific
protection against a given disease. Following vaccine administration,
the immunogen stimulates the immune system to produce active
immunity in the form of protective antibody and/or immunocompetent
T cell response.

3. Types Of Vaccines
1. Live attenuated
2. Killed whole organism
3. Subunit vaccines
4. Combination vaccines
A. Toxoids
B. Protein vaccines
C. Recombinant protein vaccines
D. Polysaccharide based vaccines
E. Conjugate Vaccines

4. Vaccines Currently In use
Live Attenuated Killed Toxoid/Protein Polysaccharide Glycoconjugate Recombina
nt
1. Tuberculosis
(BCG)
2. Yellow fever17D
3. Polio (OPV)
4. Measles Mumps
5. Rubella
6. Typhoid
7. Varicella
8. Rotavirus
9. Cholera
10. Zoster
1. Typhoid
2. Cholera
Plague
3. Pertussis
4. Influenza
5. Typhus
6. Polio (IPV)
7. Rabies
8. JE
9. TBE
10. HAV
1. Diphtheria
2. Tetanus
3. Acellular Pertussis
4. Anthrax
5. Influenza subunit
1. Pneumococcus
2. Meningococcus
3. Hib
4. Typhoid (Vi)
1. Hib
2. Pneumococus
3. MenACWY
1. HBV
2. Lyme
disease
3. Cholera
toxin B
4. HPV
BCG-Bacille Calmette-Guerin; HAV-hepatitis A virus; HBV-hepatitis B virus: Hib-Haemophilus influenzae type b; IPV
inactivated polio vaccine; JE-Japanese encephalitis; Men - meningococcus; OPV-oral polio vaccine; TBE-tick-borne
encephalitis.

5. Live Attenuated Vaccines
• Live vaccines, such as BCG are prepared from live (usually attenuated)
organisms.
• The live attenuated organisms lose their ability to induce full blown
disease, but retain their immunogenicity
• Attenuation is achieved by passing the live organisms serially through
a foreign host, such as chick embryo/ tissue culture or live animals.

6. Live Vaccines
Bacterial Viral
• BCG vaccine
• Typhoid vaccine
• Epidemic typhus vaccine
• Measles vaccine
• Mumps vaccine
• Rubella vaccine
• Live attenuated influenza vaccine
• Chickenpox vaccine
• Oral polio vaccine (OPV, Sabin vaccine)
• Rotavirus vaccine
• Yellow fever 17D vaccine
• Hepatitis A vaccine
• Japanese B encephalitis vaccine (14-
14-2 strain)

7. Killed Vaccines
• It consists of organisms, which are grown in culture under controlled
conditions and then killed using methods, such as heat or
formaldehyde.
• They are generally safer but less efficacious than live vaccines
• Compared to the live vaccines, killed vaccines require large doses,
adjuvants, and multiple doses to confer immunity. In most cases, a
booster dose is also needed
• Adjuvants increase the immunogenicity of the vaccine antigen (e.g.
alum is used as adjuvant in DPT vaccine)
• Killed vaccines are usually administered in subcutaneous or
intramuscular routes. The only absolute contraindication is a severe
local or general reaction to the previous dose.

8. Killed Vaccines
Bacterial Viral
• Typhoid vaccine
• Cholera vaccine
• Pertussis vaccine
• Plague vaccine
• Injectable polio vaccine (IPV or Salk
vaccine)
• Killed influenza vaccine
• Rabies vaccine
• Hepatitis A vaccine
• Japanese B encephalitis vaccine
(Nakayama strain)

9. Killed vs Live vaccines
Characteristic Killed Vaccine Live Vaccine
Number of doses Multiple Single*
Need for adjuvant Yes No
Duration of immunity Shorter Longer
Effectiveness of protection Lower Higher
Mimics natural infection Less closely More closely
Immunoglobulins produced IgG IgA and IgG
Mucosal immunity Absent Present
Cell-mediated immunity Poor Induced
Reverts back to virulent form No May be
Excretion of vaccine virus and transmission
to non-immune contacts
No Possible
Interference by other microorganisms in
host
No Possible
Stability at room temperature High Low
Immunodeficiency and pregnancy Safe Not Safe

10. Cholera vaccines
Injectable Killed Vaccines
They are no longer in use, as they provide little protection, cause
adverse effects and fail to induce a local intestinal mucosal immune
response.
Oral Cholera Vaccines
Oral cholera vaccines (OCV) are currently in practice. Two types of oral
vaccines are available.
Killed Whole-cell vaccine:
1. Whole-cell (WC) vaccine: It is composed of killed whole cells of V.
cholerae 01 (classical and El Tor, Inaba and Ogawa).
2. Whole-cell recombinant B subunit cholera vaccine (WC/TBS)
(Dukoral): Composition is same as that of WC vaccine, in addition it has
recombinant cholera toxin B subunit.

11. • Schedule: Two doses are given orally, at 7 days gap except for children
2-5 years (3 doses). It is not licensed for children less than 2 years
• Protection is short lived. For the first 6 months after vaccination, the
protection rate is around 58% for WC vaccine and 85% for WC/rBS
vaccine. However, it falls rapidly to 50% by 3 years of vaccination
• Children are better protected than adults
• WHO recommends for using vaccine during epidemics and outbreaks
in the community but not during inter epidemic period.
Cholera vaccines

12. 1. Parenteral heat-phenol-inactivated vaccine (TAB Vaccine)
manufactured by Wyeth, that has been widely used for many years.
• Typhoid vaccine is a suspension of killed Salmonella typhi, containing
not less than 1,000 million bacteria of S. Typhi Ty-2 strain and 500
million each of Salmonella typhi A & B strains per human dose of 1 ml
• Primary immunization with this parenteral vaccine consists of 2 doses
given 4 weeks apart with a single booster dose recommended every
three years.
• 0.5 ml of vaccine is given in two subcutaneous doses at an interval of
4-6 weeks, which is followed by intradermal injection of 0.1 ml every
three years.
• This vaccine induces only humoral immunity but no local or cellular
immunity
Killed Typhoid vaccines

13. 2. Alcohol inactivated vaccine: It is superior to heat inactivated
vaccine as Vi antigen is preserved.
3. Acetone inactivated vaccine: The cultures are inactivated using
acetone, then air dried or lyophilized. Vi antigens are preserved.
4. Formalin inactivated phenol preserved vaccine: Cultures
inactivated using formalin and vaccine is preserved using phenol.
Killed Typhoid vaccines

14. Pertussis vaccine
• Whole-cell Pertussis Vaccine: It is prepared by heating followed by
chemical inactivation and purification of whole B. pertussis bacilli.
• Efficacy is good, average being 85%
• DPT vaccine: In India and many other countries, whole cell (WC)
pertussis vaccine is given under national immunization programme,
along with diphtheria toxoid and tetanus toxoid. Three doses of
pentavalent vaccine (DPT, hepatitis B and H. influenzae) are given at 6,
10 and 14 weeks, followed by two boosters of DPT at 1½ years and 5
years. Pertussis component acts as an adjuvant and increases
immunogenicity of DT and TT
• Dose and route: 0.5 ml IM AL Thigh

15. Adverse effects: WC vaccine is associated with the following adverse
effects, such as:
• Common: Fever, injection-site pain, erythema, swelling, and
irritability
• Uncommon:
i. Persistent (>3 hours) inconsolable screaming
ii. Seizures
iii. Hypotonic, hypo responsive episode (HHE)
iv. Anaphylaxis
v. Encephalopathy
Pertussis vaccine

16. Contraindications: Because of the adverse effects, the WC vaccine is
contraindicated in
• Children more than 5-6 years age
• Any associated progressive neurological conditions
• Children with strong family history of epilepsy
• Hypersensitivity to previous dose.
Pertussis vaccine

17. Plague vaccine
• Formalin killed vaccine Sokhey's modification of original Haffkine
vaccine. It is prepared in Haffkine institute, Mumbai
• Schedule: It is given subcutaneously, two doses 4 weeks apart and a
booster given after 6 months. It is contraindicated in infants <6
months
• Protection is short-lasting (<6 months)
• Drawbacks: It is not protective against pneumonic plague and has
considerable side effects.

18. IPV
• Discovery: Jonas Salk had prepared IPV in HeLa cells in 1952. It was
announced to the world by Dr Thomas Francis in 1955.
• Cutter incident (named after the manufacturer): An outbreak of
vaccine induced paralytic poliomyelitis had occurred in America
(1955) that had killed more than 100 people. It was due to improper
inactivation of IPV. Vaccine was modified later, after which it has been
completely safe

19. IPV
• Preparation: Virus is grown in monkey kidney cell line and inactivated
by formalin. Each dose (0.5 mL) of vaccine contains total 80 units of
D-antigen of all the three poliovirus serotypes
• 40 units of type 1
• 8 units of type 2 and
• 32 units of type 3
Dose: IPV can be given either as
(i) full dose (0.5 mL dose), intramuscular (IM) route at thigh
(ii) as fractional dose (0.1 mL intra dermal ID route at upper arm

20. National immunization Schedule (India):
• In 2015, IPV was introduced in national immunization program as
single full dose (IM route) at 14th week along with bivalent OPV
• Since 2017, f-IPV is administered by ID route scheduled at 6th and
14th weeks of age along with bivalent OPV.
This change was made because
(i) 2 f-IPV, given by ID route at 6 and 14 weeks had shown to provide
higher seroconversion rates than a single full dose (IM) given at 14
weeks and
(ii) cost saving (0.2 mL/2 doses of f-IPV vs 0.5 mL of full dose IPV).

21. Differences between injectable and oral polio vaccines
Properties Salk(IPV) Sabin(OPV)

22. Inactivated Influenza Vaccine (IIV) Fluzone
• It is prepared by growing the vaccine strains in allantoic cavity of
embryonated chick eggs and then harvested, purified, inactivated by
formalin or beta propiolactone and then standardized based on
hemagglutinin antigen content (15 µg of HA/ dose).
• Schedule: Single dose administered by intramuscular Route; except
for 6 months-8 years of age (2 doses are required ≥4 weeks apart)
• Timing of vaccination: Optimally before onset of influenza season, i.e.
by end of October

23. Fluzone
• Efficacy: The vaccine efficacy varies from 25-67%
 25% for H3N2,
 42% against type B and
 67% against HINI
• Immunity lasts for 6-12 months
• Side effects: Mild reactions can occur in 5% of cases such as redness
at injection site, fever and aches. Serious side effects such as asthma,
multisystemic allergic reactions can occur very rarely.

24. Fluzone
• Indications: Routine annual influenza vaccination is recommended for
all persons aged ≥6 months who do not have contraindications.
High-risk groups should be given first priority for vaccination
• Age:≥6 months to <5 years and ≥50 years
• Persons with chronic pulmonary, cardiovascular, renal, hepatic,
neurologic, hematologic, or metabolic disorders
• Low immunity e.g. HIV infection, Pregnant women
• Those receiving aspirin
• Extremely obese (body mass index ≥40)
• Caregivers and contacts of those at risk, e.g. health care workers and
household contacts.

25. Fluzone
Contraindications: IIV should not be administered to people who have
allergy to eggs or have history of hypersensitivity to previous dose of
vaccine
Travelers: If traveling to an area of increased influenza activity; can
consider vaccination, preferably 2 weeks before departure.

26. Killed Rabies Vaccine
• These are derived from the nervous tissues of animals infected with
the fixed rabies virus. It was developed by Louis Pasteur and modified
later.
• Neural vaccines were in use in India for quite a long time, but they are
encephalitogenic, poorly immunogenic and are associated with
serious risk of neurological complications which occur due to the
myelin component of vaccine which is encephalitogenic. They are no
longer in use since 2004 and have been replaced by non-neural
vaccines

27. • Semple vaccine: It is derived from infected sheep brain, inactivated
with phenol
• Beta propiolactone (BPL) vaccine: It is a modified Semple vaccine
which is inactivated with beta propiolactone instead of phenol. It was
earlier prepared by Pasteur Institute of India, Coonoor, Tamil Nadu
• Infant Mouse Brain Vaccine: It is derived from infected neural tissue
of newborn mice.
Killed Rabies Vaccine

28. Inactivated Hepatitis A vaccine
• Formaldehyde inactivated vaccine: It is prepared from human fetal
lung fibroblast cell lines such as MRC-5 and WI 38.
• It is given to children after 12 months of age.
• Single dose is administered by IM (deltoid) followed by booster at 6-
12 months gap.
• Its protective efficacy is about 94%
• Vaccine is highly immunogenic and immunization will generate long-
lasting, possibly life-long, protection against the disease in children
and adults.
• Combination of hepatitis A and B, or hepatitis A and typhoid vaccines
have been developed, mainly intended for use in adult travellers.

29. Inactivated JE vaccines
Inactivated vaccine Nakayama strain and Beijing strain
• Both are mouse brain derived and formalin inactivated
• Prepared in Central Research Institute, Kasauli (India).
• Drawback is limited duration of induced immunity and need for
multiple doses
Inactivated vaccine Beijing P3 strain: It is a cell line derived vaccine
• manufactured and widely used in china

30. • Immunisation Schedule: When immunizing children 1-3 years of age
the mouse brain-derived vaccine provides adequate protection
throughout childhood following 2 primary doses 4 weeks apart, and
boosters after 1 year and subsequently at 3-yearly intervals until the
age of 10-15 years.
• For travellers aged ≥1 year, visiting rural areas of endemic countries
for at least 2 weeks, the established current practice is to administer 3
primary doses at days 0,7 and 28; alternatively 2 primary doses
preferably 4 weeks apart. When continued protection is required,
boosters should be given after one year and then every 3 years
• Dose and Route: 0.5ml SC Right upper arm (1ml for ≥3 years age)
• The vaccine is best used in interepidemic period
• Vaccine of swine is equally important for public heath and economic
reasons, it prevents viremia in these animals
Inactivated JE vaccines

31. Subunit Vaccines
• A vaccine can be made of single or multiple antigenic components of
a microorganism that are capable of stimulating a specific immune
response sufficient to protect from the relevant pathogen infection or
from the clinical manifestation of the disease.
• Depending on the molecular composition of the purified antigen and
on the techniques applied to obtain vaccine, different types of
subunit vaccines can be defined.

32. Subunit vaccine Types
1. Toxoids
2. Protein vaccines
3. Recombinant protein vaccines
4. Polysaccharide based vaccines
5. Conjugated vaccines

33. Toxoid
• Toxoid is the form of toxin which loses its virulence property but
retains immunogenicity
• Certain organisms produce exotoxins, e.g., diphtheria and tetanus
bacilli.
• The toxins produced by these organisms are detoxicated by treating
with formalin or acidic pH and prolonged storage.
• The antibodies produced neutralize the toxic moiety produced during
infection, rather than act upon the organisms.
• In general, toxoid preparations are highly efficacious and safe
immunizing agents.

34. Toxoid vaccines - Examples
Toxoids
1. Diphtheria
2. Tetanus

35. Diptheria Toxoid
• Diphtheria toxin is antigenic and antitoxins are protective in nature.
However, as it is virulent, it cannot be given directly for vaccination.
• Toxin can be converted to toxoid which is used for vaccination. Toxoid
is a form of toxin, where the virulence is lost retaining its antigenicity
• Toxoid formation is promoted by formalin, acidic pH and prolonged
storage
• Park William 8 strain of C. diphtheriae is used as a source of toxin for
the preparation of vaccine
• LF unit: DT is expressed as Loeffler's flocculating (Lf) unit. 1 Lf unit is
the amount of toxin which flocculates most rapidly with one unit of
antitoxin.

36. Types of Vaccine
Single vaccine: Diphtheria toxoid (alum or formal precipitated)
Combined vaccine: Various vaccines available are:
• DPT: Contains DT (diphtheria toxoid), Pertussis (whole cell) and TT
(tetanus toxoid)
• DaPT: Contains DT, TT and acellular pertussis (aP)
• DT: Contains DT and TT
• dT: Contains TT and adult dose diphtheria toxoid (d).
• Pentavalent vaccine: DPT can also be given along with hepatitis B and
Haemophilus influenzae type b.

37. Diptheria Toxoid
Diphtheria toxoid is prepared by two methods:
• 1. Plain formol toxoid (or fluid toxoid): Toxoid is prepared by
incubating toxin with formalin.
• 2. Adsorbed (alum adsorbed): Formol toxoid is adsorbed on to alum.
Alum (Aluminum phosphate, to less extent Aluminum hydroxide) acts
as adjuvant and increases the immunogenicity of toxoid.

38. • Schedule: Under National Immunization Schedule (NIS) of India 2018,
total five doses are given. Three doses of pentavalent vaccine at 6, 10
and 14 weeks of birth; followed by two booster doses of DPT at 16-24
months and 5 years.
• Site: DPT is given deep intramuscularly (IM) at anterolateral aspect of
thigh, gluteal region is not preferred as fat may inhibit DPT absorption
• Thiomersal (0.01%) is used as preservative
• Storage: DPT should be kept at 2-8°C, if accidentally frozen then it has
to be discarded
DPT

39. DPT
• Dose: One dose (0.5 mL) of vaccine contains:
Glaxo: 25 Lf (DT), 5 Lf (TT), 20,000 million (pertussis killed bacilli)
Kasauli: 30 Lf (DT), 10 Lf (TT), 32,000 million (pertussis killed bacilli).
• Td: It contains TT and adult dose (2 Lf) of diphtheria toxoid. It is
recommended after 7 years
• Tdap: It is an adult tetanus-diphtheria-acellular pertussis vaccine. This
can be given safely to older children, as this form of pertussis vaccine
is devoid of neurological complication
• Protective titer: Following vaccination, an antitoxin titer of ≥ 0.01
unit/mL is said to be protective

40. DPT vaccine
• Adult immunization: As adult diphtheria cases are increasingly being
reported, adult immunization by Td vaccine has been recommended
• For adults>18 years who have completed their primary vaccination
schedule, a booster dose of Td vaccine is indicated once in every 10
years till the age of 65
• For adults >18 years who have not completed their primary
vaccination schedule: 3 doses of Td given at 0, 1 month, and 1 year.

41. Adverse Reactions following DPT Administration
Mild: Fever and local reaction (swelling and indurations) are observed
commonly
Severe: Whole cell killed vaccine of B. pertussis is encephalitogenic. It is
associated with neurological complications. Hence, DPT is not
recommended after 6 years of age
Absolute contraindication to DPT:
Hypersensitivity to previous dose, Progressive neurological disorder.
DPT vaccine

42. Tetanus Toxoid
Tetanus toxoid (TT) is commonly used for active immunization. It is
available either as:
Monovalent vaccine:
Plain formal toxoid (or fluid toxoid): Toxoid is prepared by incubating
toxin with formalin
Adsorbed: Formol toxoid is adsorbed on to alum.
Combined vaccine: DPT (consists of diphtheria toxoid, pertussis
whole cell killed preparation and tetanus toxoid)

43. • Primary immunization of children: Tetanus toxoid is given under
National Immunization Schedule of India. Total seven doses are given,
three doses of pentavalent vaccine at 6, 10 and 14 weeks of birth,
followed by two booster doses of DPT at 16-24 weeks and 5 years
followed by two additional doses of TT at 10 years and 16 years
• Adult immunization: If primary immunization is not administered in
childhood, then adults can be immunized with tetanus toxoid, Four
doses of TT is given; 2 doses of TT at 1 month interval followed by 2
booster doses at 1 year and 6 years.
Tetanus Toxoid

44. • Site: TT is given by deep intramuscular route at anterolateral aspect
of thigh (children) and in deltoid (adults)
• Protective titer: Persons are said to be protected if tetanus antitoxin
titre is ≥0.01 unit/mL.
Adverse reactions
• Minor: local reaction, Pain
• Major: Brachial neuritis, Anphylaxis
Tetanus Toxoid

45. Protein Vaccines
• In case, immunization with a single protein or a combination of
proteins from a pathogen is sufficient to stimulate a protective
immune response against that particular microorganism, the
approach of a protein-based vaccine is appropriate.
• Proteins can be purified from in-vitro cultures of a pathogenic
microorganism.
• Licensed acellular pertussis vaccines currently available contain from
two to four different proteins purified from B. pertussis and are able
to confer protection against whooping cough comparable to that
obtained with the whole cell vaccine.
• One of the most widely used subunit protein vaccines is the influenza
vaccine composed of haemagglutinin (HA) and neuraminidase (NA)
purified from the inactivated influenza virus.

46. Protein Vaccines - Examples
Protien Vaccines
1. Acellular Pertusis
2. H. Influenza

47. Acellular Pertusis
• It is composed of pertussis toxoid and 2 or more other bacterial
components such as FHA, pertactin or fimbriae
• Though the efficacy is same as WC vaccine, it is associated with fewer
side effects as compared with the latter and can be safely given after
5-6 years
• It is available as DapT (along with diphtheria and tetanus toxoid)

48. Acellular pertusis
• Local reactions occur about one-tenth to one-half as frequently with
acellular vaccines as with whole-cell vaccines
• Incidence of erythema by the third evening after any of the first three
doses of acellular vaccines for children ranged from 26.3% to 39.2% in
one large comparative trial, compared with 72.7% in those who
received the whole-cell vaccine
• In that study, the incidence of fever (>39.4°C) after acellular vaccines
was 3.3% to 5.2%, compared with 15.9% after receipt of whole-cell
vaccine
• More serious adverse events, such as seizures and hypotonic
hyporesponsive episodes, also appear to occur less frequently

49. Recombinant Protein Vaccine
• Development of the recombinan DNA technology has made possible
the expression of protective protein antigens in heterologous
expression systems such as E. coli, yeast, mammalian cells.
• This technology avoids the problems related to growing and
manipulating large amounts of a pathogen from which the antigen is
purified.
• Moreover, recombinant proteins are generally better purified from
cultured microorganisms resulting in cleaner vaccine preparations
with a better safety profile.
• A drawback is their reduced immunogenicity that may require the
addition of an adjuvant to achieve enhanced efficacy.

50. Recombinant Vaccines - Examples
Recombinant Vaccines
1. Hepatitis B
2. HPV

51. Recombinant Vaccine - Hepatitis B
Gene Coding for HbsAg
Inserted into Chromosome of Baker's Yeast
Modified Yeast cell produces large amount of HBsAg
Purified and used in preparation of HepB vaccine

52. Hepatitis B vaccine
• Route of administration: Vaccine is administered by intramuscular
route over deltoid region (in infant - anterolateral thigh)
• Dosage: 10-20 ug/dose (half of the dose is given to children below 10
years)
• Schedule: Recommended schedule for adults: Three doses are given
at 0,1 and 6 months.
• Under national immunization schedule. It is given at 6,10&14 weeks
(along with DPT vaccine). Additional Birth dose is givenwith
prevalence of HBV ≥8%
• Minimal interval between dosages is 4 wks

53. • Marker of protection: Recipients are said to be protected if they
develop seroconversion with an anti-HBsAg antibody titer of more
than 10 mIU/ml
• Re-vaccination: If titer remain <10 mIU/mL after first series of
vaccination; the HCW is subjected to second series of vaccination (3
doses at 0, 1, 6 months)
• Booster doses are not needed: The health care workers once
protected, should not check their titer again or should not take
booster vaccines. They remain protective even if the titer falls <10
mIU/mL. This is because the memory cells get stimulated much faster
and the titer rises very soon following an infection with HBV.
Hepatitis B vaccine

54. • The high-risk persons for whom the vaccination is recommended are
persons with high-risk sexual behaviour, partners and household
contacts of HBsAg-positive persons, injecting drug users, persons who
frequently require blood or blood products, recipients of solid organ
transplantation, those at occupational risk of HBV infection, including
health care workers, as well as for international travellers to HBV
endemic countries.
• Contraindications: individuals with a history of allergic reactions to
any of the vaccine's components. Neither pregnancy lactation is nor
contraindication for use of this vaccine.
Hepatitis B vaccine

55. HPV vaccine
Viral Genome: Viral genome consists of an early (E) region, a late (L)
region, and a noncoding regulatory region.
• Early region genes (E1-E7): They code for early non structural
proteins. The E1 and E2 proteins modulate viral DNA replication.
Products of early genes E6 and E7 have oncogenic potential by
following ways:
E6 protein facilitates the degradation of the p53 tumor-suppressor
protein
E7 protein binds to the retinoblastoma gene product and related
proteins.

56. HPV vaccine
• Late region genes (L1 and L2): They code for structural proteins such
as capsid.
L1-codes for major capsid proteins
L2-codes for minor capsid proteins.
• Types: More than 100 types of HPV are recognized based on DNA
sequences of L1 region. Types differ from each other at least by more
than 10% in the sequence of their L1 genes.

57. • Recently developed HPV vaccines have shown dramatic reduction in
rates of all HPV infections including cervical cancers. It is
recommended to adolescent young females.
• Subunit vaccine consists of virus-like particles composed of HPV L1
proteins which are produced in yeast by recombinant DNA technology
• These vaccines Lack DNA hence non infectious
• Highly immunogenic : High levels of type specific humoral antibodies
leading to prevention of entry of HPV into epithelial cells.
HPV vaccine

58. Cervarix Gardasil Gardasil-9
Type Bivalent Quadrivalent Nonavalent
Effective against HPV 16 and 18 HPV 6, 11, 16 & 18 HPV 6, 11, 16, 18, 31,
33, 45. 52 & 58
Protects From Cervical cancer Cervical cancer and
Genital warts
Anogenital cancers
and Genital warts &
laryngeal pappilomas
Schedule 3 IM injection at 0,1
and 6 months
IM injection at 0,2,6
months
IM injection at 0,2,6
months
Dose 0.5 ml containing 20
µg HPV 16 L1
20 µg HPV18 L1
0.5ml containing
20 µg HPV6 L1
40 µg HPV II L1
40 µg HPV16 L1and
20 µg HPV18 L1
Recommended age
groups
Females 10-25 years Females 9-26years Females 9-26 years
Males 9-21 years

59. Polysaccharide Based Vaccine
• The surface of many pathogenic bacteria is covered by a capsular
shell that is mainly assembled from polymeric glycans.
• This extensive polysaccharide coat entirely shields the bacteria outer
membrane. Antibodies to the bacterial surface polysaccharides can
clear the bacteria from the host by different mechanisms, such as
complement-mediated killing and opsonophagocytosis.
• stimulation of an antibody response against the surface
polysaccharide of pathogenic bacteria is a strategy for the
development of vaccines against capsulated bacteria.

60. • The chemical structure or capsular polysaccharides varies not only
between bacteria of different species but also between different
strains within a single species.
• Immune responses they elicit are often serotype specific.
Polysaccharide Based Vaccine

61. Polysaccharide Based Vaccines
1. S. pneumoniae (PPV23)
2. MenACWY
3. Typhoid Vi
Polysaccharide Based Vaccine - Examples

62. Pneumococcal Pneumonia vaccine PPV23
• polysaccharide non-conjugate vaccine containing capsular antigens of
23 serotypes
• Available for adults and children over 2 years of age.
• Children under 2 years of age and immunocompromised individuals
do not respond well to the vaccine.
Recommended in high risk groups: Those who has undergone
splenectomy or have sickle-cell disease, chronic diseases of heart,
lung, liver or kidney; diabetes mellitus, alcoholism, generalized
malignancies, organ transplant recipients.
• In some industrialized countries like USA it is routinely advised for
everyone aged above 65 years

63. • Dose: 0.5 ml of PPV23 contains 25 micrograms of purified capsular
polysaccharide from each 23 serotypes.
• Route: single intra-muscular dose preferably in the deltoid muscle or
as subcutaneous dose.
• The vaccine should not be mixed in the same syringe with other
vaccines, for e.g. with influenza vaccine, but may be administered at
the same time by separate injection in the other arm.
• Adverse reactions: Minor adverse reactions, redness and pain at the
site of injection occur in 30-50 % , more commonly following
subcutaneous administration. Local reactions are more frequent in
recipients of the 2nd dose of the vaccine
Pneumococcal Pneumonia vaccine PPV23

64. Types of pneumococcal vaccines
PPV23 PCV13
Name 23-valent pneumococcal polysaccharide
vaccine
Pneumococcal conjugate vaccine
Serotypes included Contains 23 serotypes of S. pneumoniae
1,3,4,5, 6A, 68, 7F, 9V, 10A, 11A, 12F, 14, 5B,
17F, 18C, 19A, 19F,
20, 22F, 23F, and 33F
13 serotypes of S. pneumoniae 1, 2, 3, 4, 5,
68, 7F, 8, 9N, 9V, 14, 18C, 19A, 19F, & 23F
conjugated with diptheria toxoid
Coverage Covers 70-80% of invasive serotypes in adults Covers only 30-40% of invasive serotypes in
adults, however it covers most of the
serotypes infecting children
Immunogenicity Less immunogenic
Capsular antigen being T cell independent
antigen, is less immunogenic to children, hence
not given to children <2 years age
More immunogenic
The protein conjugate acts as adjuvant and
increases the immunogenicity of capsular
antigen. Hence, PCV is effective against
children <2 years age
Duration 3-5 years Longer duration
Herd immunity Promotes Herd immunity Does not promote
Effect on carriers Doesnot provide mucosal immunity hence no
effect on carriers
Provide mucosal immunity hence it can
eradicate carriers from nasopharynx
Cost Less expensive More expensive
Indications Adults≥65 years
Adults 19-64 with underlying risk factors
Same as PPV23
Children (as primary immunisation)

65. Meningococcal polysaccharide vaccine
• Meningococcal polysaccharide vaccines are currently formulated as
either bivalent (serogroups A and C) or quadrivalent (serogroups A, C,
Y, and W135)
• Dose: 50 µg of each polysaccharide antigen per dose is used,
administered as two doses, 2-3 months apart to children of 3-18
months of age or a single dose to older children or adults.
• Efficacy: It has a protective efficacy rate of >95%. The duration of
protection lasts for 3-5 years
• Indication: (i) contacts of patients during outbreaks, (ii) splenic
dysfunction, (iii) terminal complement component deficiency, (iv)
taking eculizumab therapy, (v) laboratory staff at risk

66. Capsular vaccine is not available for serogroup B as:
Capsule of serogroup B (made up of sialic acid) is less immunogenic
It is also encephalitogenic due to expression of similar cross reactive
antigens on neural cells.
Not given below 3 years: Similar to pneumococcal vaccine,
meningococcal capsular vaccine is also an example of T-cell-
independent antigen and is poorly immunogenic to children; hence
not given to children of less than 2-3 years of age
• Conjugated vaccine: However, conjugated meningo coccal capsular
vaccine is available which can be given to young children. Addition of
a protein carrier (adjuvant) increases the immunogenicity of the
capsular vaccine.
Meningococcal polysaccharide vaccine

67. Typhoid Vi Polysaccharide vaccine
• First licensed in United States in 1994
• It is composed of purified Vi capsular polysaccharide antigen derived
from S. Typhi strain Ty2.
• Dosage: Single dose containing 25 ug of Vi antigen is given IM or SC
• Vaccine confers protection for2-3 years booster is given every 3 years
• Age: It is given only after 2 years of age as Capsular antigen being T
independent antigen, is poorly immunogenic to children < 2 years
• Vi-rEPA: Vi antigen is conjugated with recombinant Pseudomonas
aeruginosa Exotoxin A. Conjugation increases immunogenicity of the
Vi antigen; therefore this vaccine can be given to children less than
two years.

68. Typhoid Vi
• Schedule The vaccine is licensed for individuals aged ≥ 2 years. Only 1
dose is required, and the vaccine confers protection 7 days after
injection.
• Revaccination is recommended every 3 years.
• vaccine can be co-administered with other vaccines relevant for
international travellers, such as yellow fever and hepatitis A.
• Safety No serious adverse events and a minimum of local side effects
are associated with Vi vaccination. There are no contraindications to
the use of this vaccine other than previous severe hypersensitivity
reaction to vaccine components.
• Vaccine is safe for HIV-infected individuals, the induction of protective
antibodies is directly correlated to the levels of CD4 positive T-cells.

69. Conjugated Vaccines
• Children under two years of age do not respond well to antigens, such
as polysaccharides, which produce antibodies via a T-cell
independent mechanism.
• mechanism. If these polysaccharide antigens are conjugated to a
protein that T-cells recognize, then these conjugate vaccines can elicit
strong immune responses and immune memory in young children.
• the conjugate vaccines are also sero-type specific, therefore,
multivalent formulations are required to achieve protection against
multiple serotypes.

70. Conjugated Vaccines
1. S. pneumococcal
2. Meningococcal vaccine
3. Hib comjugate vaccine
Conjugated Vaccines

71. PCV
• Two conjugate vaccines are available since 2009 PCV10 and PCV13
Both are preservative free and their recommended storage
temperature is 2-8°C. The vaccine must not be frozen.
• Schedule: WHO recommends 3 primary doses (the 3p+0 schedule) or,
as an alternative, 2 primary doses plus one booster (the 2p+1
schedule).
• In 3p+0 schedule, vaccination can be initiated as early as 6 weeks of
age with an interval betweeen doses of 4-8 weeks, with doses given
at 6, 10 and 14 weeks
• 2p+1 schedule, the 2 primary doses are given at 6 and 14 week, One
booster dose should be given between 9-15 months of age

72. • Dose and route: 0.5ml IM at anterolateral aspect of thigh
• Adverse reaction: Mild reactions like erythema and tenderness in 30-
50% cases. No proven serious reactions.
PCV

73. PCV vaccine Special Indications:

74. Types of pneumococcal vaccines
PPV23 PCV13
Name 23-valent pneumococcal polysaccharide
vaccine
Pneumococcal conjugate vaccine
Serotypes included Contains 23 serotypes of S. pneumoniae
1,3,4,5, 6A, 68, 7F, 9V, 10A, 11A, 12F, 14, 5B,
17F, 18C, 19A, 19F,
20, 22F, 23F, and 33F
13 serotypes of S. pneumoniae 1, 2, 3, 4, 5,
68, 7F, 8, 9N, 9V, 14, 18C, 19A, 19F, & 23F
conjugated with diptheria toxoid
Coverage Covers 70-80% of invasive serotypes in adults Covers only 30-40% of invasive serotypes in
adults, however it covers most of the
serotypes infecting children
Immunogenicity Less immunogenic
Capsular antigen being T cell independent
antigen, is less immunogenic to children, hence
not given to children <2 years age
More immunogenic
The protein conjugate acts as adjuvant and
increases the immunogenicity of capsular
antigen. Hence, PCV is effective against
children <2 years age
Duration 3-5 years Longer duration
Herd immunity Promotes Herd immunity Does not promote
Effect on carriers Doesnot provide mucosal immunity hence no
effect on carriers
Provide mucosal immunity hence it can
eradicate carriers from nasopharynx
Cost Less expensive More expensive
Indications Adults≥65 years
Adults 19-64 with underlying risk factors
Same as PPV23
Children (as primary immunisation)

75. Hib Conjugate vaccine
• The polyribosyl ribitol phosphate (PRP) capsular antigen of H.
influenzae type b is used for vaccination.
• As capsular antigens are poorly immunogenic to children, they are
conjugated with adjuvants such as diphtheria toxoid, tetanus toxoid
and N. meningitidis outer membrane proteins
• In addition to eliciting protective antibody, this vaccine can also
reduce the rate of pharyngeal colonization with Hib
• Schedule: Under national immunization program, Hib vaccine is given
in combination with DPT, hepatitis B (pentavalent vaccine) at 6, 10
and 14 weeks of birth.
• It is administered in IM route, at anterolateral side of mid thigh

76. • For children more than 12 months of age, who have not received
their primary immunization series a single dose is sufficient for
protection
• The vaccine is not generally offered to children aged more than 24
months
• side-effects: Local reaction, Pain, redness, fever in 2-10% cases
• No known contraindications, except for hyper-sensitivity to previous
dose of vaccine. All conjugate vaccine have an excellent safety record
• Do not interfere substantially with immunogenecity of other vaccines
given simultaneously
Hib Conjugate vaccine

77. References
• K Park 25th edition
• Essentials of Medical Microbiology - Apurba Sastry

78. THANKYOU