newer vaccine

1. NewerVaccines
Prospects and Challenges
Presented by
Dr. Akhilesh Kr. Tripathi
Moderator
Prof. Ratan K. Srivastava

2. Outline of Presentation
• Introduction
• Milestones of Vaccine development in India
• Newer vaccines – its need, Relevance and Challenges
• Introduction of new vaccines in UIP – Guiding Principles
• Revised National Immunization Schedule 2019
• Recently developed or introduced vaccine
• Pipeline Vaccines- HIV, MALARIA, LEPROSY, TB, CANCER
and DIABETES Vaccine DNA Vaccines and EDIBLE vaccine.
• Newer Technologies Of Vaccine Delivery.
2

3.  One of the greatest impacts on the health of mankind has been
the use of vaccines.
 Vaccination as a deliberate attempt to protect humans against
disease.
 Immunization is process by which immune system become
fortified against an agent.
 The eradication of smallpox was not only a global public health
victory but also a turning point in public health strategy
 Since their acceptance as a public health intervention, vaccines
have been instrumental in bringing about a reduction of morbidity
and mortality due to vaccine preventable diseases globally
3
INTRODUCTION

4.  “A vaccine is a biological preparation that improves immunity to a
particular disease”
 A vaccine typically contains an agent:
 Resembles a disease-causing microorganism
 Often made from weakened or killed forms of the microbe, its
toxins or one of its surface proteins
 The agent stimulates the body's immune system to recognize the
agent as foreign, destroy it, and “remember” it, so that the
immune system can more easily recognize and destroy any of
these microorganisms if encounters later.
4

5. What is so special about vaccines?
 Vaccines help save lives
 Benefit not only individuals but also communities, and even
entire populations (Herd immunity) e.g. Polio, Diphtheria
 For most vaccines, their impact on communities and
population is more rapid than that of many other health
interventions, and cost saving (e.g. small pox, polio,
measles )
 Reduce prevalence and incidence of diseases, sometimes
eradicates the disease itself (small pox)
CDC has put vaccination on the top of its list of
ten great public health achievements of the 20th
century
“With the exception of safe water, no other
intervention, not even antibiotics, has had such a
major effect on mortality reduction”
5

6. IMMUNISATION MILESTONES-INDIA
1978 Expanded Programme of Immunization: BCG,DPT,OPV,Typhoid
1983 TT vaccine for pregnant women
1985 Universal Immunization Programme- Measles added, typhoid
removed, Focus on children less than 1 year of age
1990 Vitamin-A supplementation
1995 Polio National Immunization Days
1997 VVM introduced on vaccines in UIP
2002 Hep B introduced as pilot in 33 districts and cities of 10 states
2005  NRHM launched
 Auto Disable (AD) syringes introduced into UIP
2006 JE vaccine introduced after campaigns in endemic districts
2007-
08
Hep B expanded to all districts in 10 states and schedule revised from
3 to 4 doses
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7. 7
2010 Measles 2nd dose introduced in RI (14 states)
2011  Hep B universalised and Hib introduced as Pentavalent in 2 states
 Open Vial Policy for vaccines in UIP
2013  Pentavalent expanded to 9 states
 Second dose of JE vaccine
2014 India and South East Asia Region certified POLIO-FREE
2015  India validated for Maternal and Neonatal Tetanus elimination
 Pentavalent expanded to all states
 IPV Introduced
 New vaccines introduction announced – Rotavirus, Pneumococcal
and Measles/ Rubella
2016 Rotavirus vaccine introduced in 4 states in Phase 1.
2017 Rotavirus vaccine expanded 11 state by end of 2018
PCV introduced in UIP in selected district of Bihar, HP & UP
MR Campaign
2018 Rotavirus vaccine expanded to 28 state and 9 UTs.
Leprocy vaccine(MIP) introduced

8. SITUATIONAL ANALYSIS
 Today 1 out of 5 children immunized worldwide .
 In India annual cohort of infant 27 million and 30 million
pregnant women.
 9 million routine immunization (RI) sessions in each year
organized.
 67% of children are fully immunized in India and in Uttar
Pradesh 51.1% and in Varanasi 59% (NFHS-4).
 83% full immunization coverage in India till nov. 2018 (target
90% till december 2018) with annual immunization growth
rate increased 1% to 4%, with a unprecedented 16% rise in
number of fully immunized children.(Union health ministry’s
internal data.) 8

9. NEWER VACCINES and their
RELEVANCE
 ‘New’ is relative:
New to the Immunization program
New because of recent discovery
New to the specific market or region (after Licensing)
 Introduction of a New vaccine may be
Vaccine against a disease not previously covered by
immunization
New product formulation of a vaccine (e.g., a liquid
vaccine replacing a lyophilized vaccine)
New combination vaccine (e.g., DTP-HepB-Hib replacing
previous individual vaccines)
 Vaccine that uses a new route of administration in place
of a currently-used vaccine (e.g., an injectable vaccine
replacing an oral vaccine) 9

10. Need for development of newer
vaccines !!
 No effective vaccine available for major mortality causing
diseases like Malaria, TB and AIDS
 Need for effective, potent & stable vaccines
 New Delivery Techniques for better compliance
 Lower cost
 Protect against more diseases & sustained protection
 Emerging and Re-emerging Diseases
 Era of progressing antibiotic resistance
 Certain Pandemic Non-Infectious Diseases
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11. CHALLENGES…
 Weak VPD surveillance system
 Limited economic evaluations to show cost-effectiveness of
vaccines over other interventions to support decision-making
 Lack of financial sustainability plan for the introduction of new
vaccines : Biggest challenge
 Shortage of trained and skilled manpower to manage UIP
 Will country of size and resources (i.e. India) ever be able to
produce geographically representative data for rare conditions
which are often available for developed countries?
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12. Cont…
 Should we increase coverage with existing vaccines prior to
introducing new ones?
 Is decision making technical or political?
 Where to initially roll out- better performing or poor performing ?
High burden or low burden states?
 Funding, slow regulatory approval and dependence on
government persist as challenges for vaccine development in
India
 Challenge in order to provide the best available services in an
appropriate, affordable, and cost-effective manner
12

13. PRINCIPLES FOR ADDING VACCINES TO NATIONAL
IMMUNIZATION PROGRAMMES
 A strong country-led, evidence-based decision-making, planning
and prioritization process that is accountable and coordinated
with other components of the health system
 A well-performing or improving and responsive immunization
program.
 Opportunity to achieve:
 Well trained workforce
 Functional cold storage, logistics and vaccine information
13
INTRODUCTION OF NEW VACCINES
IN UIP

14.  Safe immunization practices and monitoring of adverse events
 High quality monitoring and evaluation (of VPDs and coverage)
 Maximizing opportunities to deliver vaccines as integral
components of comprehensive health promotion and disease
prevention
 Sufficient allocation of human and financial resources to introduce
the new vaccine and sustain its uses
 Uninterrupted, sufficient supply
14

15. In INDIA, who decides…
• Recommendations on specific vaccines or strategies made by the
National Technical Advisory Group on Immunization (NTAGI)
• Decisions made whether to accept the recommendations by the
Ministry of Health and Family Welfare, which has to ensure that
the funding is approved
• For ensuring the quality and safety we have National regulatory
authority and Drugs Controller General of India with many
additional committees:
• Mission Steering Group of the NHM
• Vaccine Introduction Working Group of MOHFW
• Inter-agency coordinating committee
• Health sector coordinating committee etc.
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16. NATIONAL TECHNICAL ADVISORY GROUP ON
IMMUNIZATION (NTAGI)
• Chaired by Health Secretary
• Has a technical sub-committee (TSC) co-chaired by
Secretary-Health Research and Secretary-Department of
Biotechnology
• NTAGI TSC comprised of independent experts
• Immunization Technical Support Unit serves as Secretariat
• External and internal experts invited to present to NTAGI
TSC
• Recommendations reviewed at full NTAGI meeting
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17. VACCINE SELECTION
 IDENTIFYING VACCINES OF LOCAL RELEVANCE :
 Is there a significant disease burden?
 Is the disease a priority? For the National Health Plan? For the
medical community? For the public?
 Is it recommended by WHO?
 Data from countries with geographical proximity/similar demography
used for decision-making
 A mid-term (5-7 years) strategy on the required evidence with regard
to burden of disease should be in place
 A multi-agency policy unit to conduct meetings of various
stakeholders to evaluate and monitor the studies
17

18. CRITERIA FOR SELECTION OF VACCINES
FOR INTRODUCTION
◦ Disease burden.
◦ Safety & efficacy of Vaccine under consideration
◦ Affordability & financial sustainability.
◦ Program capacity to introduce a new antigen,
including cold chain capacity
◦ Cost effectiveness of the vaccination program.
◦ Uninterrupted supply.
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19. NATIONAL IMMUNIZATION SCHEDULE
2019
Age Vaccines given
Birth BCG, bOPV-0 Dose, Hepatitis B birth dose
6 weeks bOPV-1, Pentavalent-1, Rotavirus vaccine(RVV)-1л, fIPV-1, PCV-1л
10 weeks bOPV-2, Pentavalent-2, RVV-2л
14 weeks bOPV-3, Pentavalent-3,fIPV-2, RVV-3л, PCV-2л
9-12 months MR-1#,JE-1*,PCV-Boosterл
16-24 months MR-2#, JE-2*, DPT-Booster-1, bOPV-Booster
5-6 years DPT-Booster-2
10 years TT
16 years TT
Pregnant Mother TT-1,2 or TT- Booster**
* In Endemic districts only
**One dose if previously vaccinated within 3 years
Л Rotavirus vaccine & PCV in selected states (UP tarai region, Andhra Pradesh, Haryana,
Himachal and Odisha)

20. Sequence of administration
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21. DENGUE VACCINE
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22. New Dengue vaccines-Challenges
 Viral interference
 Lack of an appropriate animal model
 Instant mice mortality
 Absence of symptoms in Non-human primate
models
 Absence of an established neutralising antibody level
 Primary vaccine efficacy
22

23. DENGUE VACCINE
(DENGVAXIA)
 World’s first vaccine against Dengue
 By Sanofi Pasteur – first licensed in December, 2015, in Mexico
 Registered for use in individuals 9-45 years of age living in endemic
areas
 CYD-TDV – live recombinant tetravalent vaccine
 3-dose vaccine given on a 0/6/12 month schedule only who had
previously infected and then do go to contact the disease.
23

24. DENGVAXIA (CYD-TDV)
 The pre-membrane and envelope proteins from a wild type dengue
virus are substituted into the yellow fever (YF) 17D vaccine
backbone
 The first phase I study in children was conducted in the dengue non-
endemic region of Mexico City
 Vaccine efficacy of CYD against all serotypes was 30.2%
 Vaccine efficacy 56.5% (Asian countries)
 Vaccine efficacy 60.8% ( Latin America)
 Approved for use in 11countries
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India doubtful even after WHO lights green signal for dengue
vaccine: More data is needed for its universal acceptance

25. Vaccine in progress
 DENVax or TAK-003 : based on recombinant
chimeric vaccine with DENV1,DENV2 ,DENV3
and DENV4. it produced sustained antibody
response ,regardless of previous dengue
exposure.
 TetraVax-DV: Tetravalent admixture of
monovalant vaccine that were tested seperately
for safety and immunogenicity.
 Both vaccine are under trail in USA, Thiland,
Brazil and Singapore.
25

26.  Contains 5 antigens (DPT + Hep.B + Hib)
 In UIP in India, Liquid vaccine available in 10 dose vials is being used
 Dose : 0.5 ml; 3 doses at 6, 10 and 14 weeks
 Targeted for children aged <1 year
 Booster dose is not recommended in India
 Common S/E : Redness, swelling and pain at injection site, fever,
irritability for short period
 AEFI is not higher than that reported with DPT vaccine alone
 Complete vaccine series induces protective efficacy of 95%
26
PENTAVALENT
VACCINE

27. FDA Approved HPV Vaccines
◦ Gardasil (2006)
◦ Cervarix (2009)
◦ Gardasil 9 (2014)
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HUMAN PAPILLOMA VIRUS (HPV) VACCINE

28. GARDASIL®9 (2014)
 HPV, Non-infectious recombinant 9-valent vaccine prepared from
purified virus-like particles (VLPs) of major capsid (L1) protein of
HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58
 MOA:
Humoral immune response
Exact mechanism of protection unknown
 Dosage & administration:
◦ 0.5-mL suspension for I.M. injection
◦ 0, 2 months, 6 months
Source: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.,
28

29.  Indications:
Girls & women 9-26 years
Boys & men 9-26 years
 Contraindications:
Hypersensitivity, including severe allergic reactions after a
previous dose of GARDASIL 9 or GARDASIL
Pregnancy
 ADR: Headache, Injection site pain, erythema, swelling
 Not included in national immunization schedule.
 High cost of vaccine
 Lack of public awareness
 Make it cost-effective: “Make in India”
29

30. 30
Vaccine Rotarix™ vaccine(The
monovalent human ) 2007
RotaTeq™ vaccine(pentavalent
bovine–human) 2005-06
Indications/
Age
Infants: 2 and 4 months of age. Infants: 2, 4 and 6 months of age
Route Orally 2 doses Orally 3 doses
Schedule 1st dose at 6 wks & 2nd at 16 wks.
Interval b/w 2 doses at least 4wks
1st dose at 6 wks and 2nd, 3rd
doses at an interval of 4 wks
Side effects Mild & transient symptoms of
gastrointestinal or respiratory
tract
Mild & transient symptoms of
gastrointestinal or respiratory
tract
Contra
indications
Hypersensitivity, history of
intussusception or intestinal
malformations, febrile illness
Hypersensitivity, history of
intussusception or intestinal
malformations, febrile illness
ROTAVIRUS VACCINE

31.  To reduce the burden of diarrhea caused by Rotavirus, the
government introduced indigenous Rotavirus vaccine
(Rotavac) in March 2016 in UIP in phase manner of four
states of Andhra Pradesh, Haryana, Himachal Pradesh and
Odisha.
 It has been expanded 11 state by end of 2018 but now it
expanded to 28 state and 8 UTs.
 The vaccine is provided as three doses at 6, 10 and 14 weeks
of age 31

32. Measles-Rubella(MR)Vaccine
 India launched one of the world’s largest vaccination campaigns
against Measles and Rubella with technical support from WHO on 5th
February, 2017
 Launched in 5 states/UTs - Karnataka, Tamil Nadu, Puducherry,
Goa and Lakshadweep covering nearly 3.6 crore children. The
campaign is targeted at vaccinating more than 41 crore children in the
age group of 9 months to less than 15 years over the next 2 years
across the country
 MR vaccine has been introduced in routine immunization and has
replaced measles vaccine, given at 9-12 months and 16-24 months of
age, in selected states
 Till Dec 2018, more than 20 crore children have been provided MR
32

33. JAPANESE ENCEPHALITIS
(JE) VACCINE
• JE vaccine SA-14-14-2 (live vaccine) was added to NIP in selected
endemic districts in phased manner since 2006 onwards
• Initially through mass campaign: 1-15 years (one dose during
outbreak/ahead of outbreak)
• Since 2013, became a part of ROUTINE IMMUNIZATION
in identified 181 high burden districts in 2-dose schedule
• JE-1: 9-12 months
• JE-2 : 15-18 months
• 2 types of JE vaccine are widely available
• Inactivated mouse-brain-derived vaccine (IMB)
• Cell-culture-derived live attenuated SA 14-14-2 vaccine
33

34. JE SA 14-14-2 VACCINE
 Live vaccine 80% efficacy with one dose, Can be given even
at 9 months, One being used in our National Program
 Dose: 1.0 ml for adults, 0.5 ml for children.
 Booster: single booster dose given at an interval of about 1
year
 Contraindications:
 Hypersensitivity to a previous dose of vaccine
 Pregnancy and immune-suppression
 2 Other types are: JEEV and JENVAC
34

35. Adult JE vaccine
 Japanese Encephalitis vaccination in children was
introduced in 2006. However, the vaccine was expanded in
adult population in state with high disease burden of adult
JE in 2015
 A total of 31 districts have been identified for adult JE
vaccination in the states of Assam, Uttar Pradesh & West
Bengal; and the Adult JE vaccination campaign has been
completed in 21 districts during which 2.6 crore adults(˃15-
65 years) were vaccinated with JE vaccine.
35

36. Oral Cholera
Vaccine
 Three type of oral cholera vaccine are available : Dukoral ,Sanchol and
Euvichol.
 Recently live oral cholera VA 1.4 vaccine developed by NICED, Kolkata.
 66% sero-conversion using only one dose of the vaccine, more protective
than the currently available one.
 The results of the human clinical trial of vaccine has been published
 The biggest differentiating factor is that unlike other three vaccines, the strain
used in the VA1.4 vaccine does not have the gene that produces the cholera
toxin.
 2main advantages:
 Single dose confers higher levels of protection
36

37. HIV VACCINES
PIPELINES VACCINES

38. HIV Vaccine development : Scientific
CHALLENGES
 Absence of spontaneous recovery from natural infection : natural
immunity fails to clear HIV
 Antigenic diversity and hyper variability of the virus
 Transmission of the disease by mucosal routes : need to block
infection at mucosal surfaces
 Integration of the viral genome into host cell chromosomes : short
window of opportunity to control
 Persistence of the virus in a latent state in resting memory T cells
 Difficult to generate broadly neutralizing antibodies
 Lack of an ideal HIV-1 animal model, requiring long and expensive
human clinical trials
38

39. 39

40. HIV vaccine
 Urgent global priority
 Realistic goal of HIV vaccine: to prevent viremia
40
Candidate
Vaccine
Component
First generation Based on envelope proteins especially gp120
Second generation Live vectors (such as canarypox) or naked
DNA coding for different HIV genes
Third generation Regulatory non-structural proteins eg. Tat (a
transactivator of HIV gene expression) and
Nef (a multifunctional protein)
Majority of these vaccines are in phase I and phase II trials.

41.  Combination of two
vaccines,
Modified poxvirus
expressing HIV antigen
and
Protein subunit vaccine
 Lowered rate of HIV
infection by 31.2 % with
41
HIV Vaccine – RV-144

42. HIV vaccine efficacy trial -RV144
 Tested the “prime-boost” combination of two vaccines:
 ALVAC HIV vaccine (Prime)
 AIDSVAX vaccine (Boost)
 ALVAC is a recombinant canary pox vector vaccine that express
antigens of HIV-1 subtypes B (gp41 ) and E (gp 120)
 AIDSVAX is a bivalent HIV envelope glycoprotein 120 vaccine
 IgG3 antibodies binding to the V1/V2 region of HIV’s envelope
protein correlated with lower infection rates among those who
were vaccinated.
42

43.  Tuberculosis Research Centre (TRC), Chennai – first phase of HIV
vaccine trial for HIV-1 subtype C from September, 2005
 2 stages in phase (24 months)
Low dose vaccine -- administered to 16 volunteers
High dosage vaccine – 2nd group of 16 volunteers
 Results (August, 2008):
 Vaccine SAFE at both low & high doses
 HIV specific immune response (after all 3 injections)
Low dose – 82%; High dose – 100%
 HIV vaccine trial – National AIDS Research Institute (Pune) to test a
different vaccine candidate - tgAAC09 (Adeno-associated Virus)
43

44. MALARIA VACCINE
MALARIA VACCINE

45. Challenges in developing Vaccine against
parasites
Larger genomes
Antigenic diversity
Multiple stages of their life cycles
 In fact there is no vaccine in the market for prevention of
any human parasitic infection
 Effective malaria vaccine still NOT there
45

46. IF THE VACCINE
TARGETS
ITS GOAL IS TO
Pre- erythrocytic
stage
Prevent infection
Blood stage Reduce clinical disease
Sexual stage or
transmission blocking
Prevent the spread of parasites by
mosquitoes
46
MALARIA VACCINE
Concept of Stage Targeting

47. RTS,S/AS01(MOSQUIRIX)
◦ 'RTS' stands for 'repeat T epitopes' derived from the sporozoite
protein; 'S' stands for the S antigen derived from Hbs antigen; AS01
is a adjuvant
 RTS,S/AS01 – most advanced vaccine candidate against most
deadly form of human malaria Plasmodium falciparum, with no
protection against P. vivax malaria
 Reconstituted 0.5mL vaccine
 Administered by intramuscular injection into:
 antero-lateral thigh in 6-12 weeks age group, and
 left deltoid in 5-17 months age group
47

48. RTS,S/AS01 TRIAL RESULTS
 Phase III trial began in May 2009 and has now completed
enrolment with 15,460 children in 7 countries in sub-Saharan
Africa
 2 groups in trial:
◦ Children aged 5-17 months: at first dose receiving only
RTS,S/AS01 vaccine; and
◦ Children aged 6-14 weeks: at first dose receiving same
malaria vaccine in co-administration with pentavalent
vaccines in routine immunization schedule.
 Both groups received 3 doses of RTS,S/AS01 vaccine at 1

49. RTS,S/AS01 – VACCINE EFFICACY
 5-17 month old children – 4 doses(0,1,2,20 month)
 6-14 weeks infants – 4 doses(6,10,14 week and 18month)
◦ RTS,S/AS01 vaccine provided protection against both
clinical and severe malaria in African children
49
39% against clinical malaria
31.5% against severe malaria
27% against clinical malaria WITH 4th dose
18% against clinical malaria WITHOUT 4th dose

50.  Many challenges continue to impede the development of an effective
vaccine despite research over the past several decades
 Malaria Vaccine Advisory Committee to WHO, coordinate Initiative for
Vaccine Research (IVR), called for a collective effort to explore and
address the challenges → Malaria Vaccine Technology Roadmap process
2006
 By 2015, develop and license a first-generation malaria vaccine that has a
protective efficacy of more than 50% against severe disease and death
and lasts longer than one year
 By 2025, develop and license a malaria vaccine that has a protective
efficacy of more than 80% against clinical disease and lasts longer than
four years
 Jointly sponsored by the Bill & Melinda Gates Foundation, the PATH 50
ROADMAP TO MALARIA VACCINE

51. LEPROSY VACCINE
 Challenges with development of vaccine for leprosy:
 Long incubation period of disease
 Paucity of animal model (Armadillo)
 Inability to culture bacteria in lab
 Complexity of immunological response to
mycobacterium.
51
Dasypus novemcinctus

52. Classification of candidate Vaccine
 FIRST GENERATION
 Non-Cultiviable
 Killed M. leprae
 Killed M. leprae + BCG
 Acetoacetylated M. leprae
 Cultiviable
 BCG
 BCG + M. vaccae
 Killed M. welchii
 Killed ICRC
 SECOND GENERATION (In vitro/ Animal studies only)
 Subunit vaccines
 Shuttle plasmid vaccines
52

53. M. Indicus Pranii (MIP Vaccine)
 This Leprosy vaccine to be launched in 2018 and
developed by GP Talwar, founder-director, NII,Delhi.
 On Pilot basis in six districts in Bihar(Banka and Jamui)
and Gujarat( Navsari, Tapi, Bhaurch, and Narmda)
 It is a preventive measures to people living in close contact
with diseased person.
 To be give along with a dose of Rifampcin.
 Trail of MIP efficacy were done in Kanpur Dehat in 2005.
Protective efficacy was 68.6% at end of 1st year, 59% at
end of 2nd year and 39.3% at 3rd year.
53

54. Cont..
 Effect of vaccine is sustained for a period of 7-8 years and
a booster does was needed to maintain immunity.
 Dosage :
1) For close contact –1ml at 0 month, 0.5 ml at 6 month and
booster dosage 0.5 ml at 5 year.
2) For Leprocy patient :
 New PB and treatment complete 2 dosage 6 month
apart and booster at 5 year.
 New MB patient : 3 dosage at 0,6 and 12 month and
booster at 5 year.
54

55. Tuberculosis Vaccine
55

56. New TB vaccines-Challenges
 Inadequate inducing substantial CD8+ T cell
responses.
 DNA vaccines have been very potent in animal studies
but in humans and other primates they have shown
only weak responses
 No biomarker found to test vaccine efficacy
 Insufficient funding.
56

57. BCG VACCINE
 Discovered by Albert Calmette & Camille Gurein.
 Live attenuated oral bovine strain of tubercle bacilli.
 WHO recommended strain “Danish 1331”.
 Two type – liquid(fresh) and freeze-dried vaccine.
 Diluent is normal saline.
 Dosage: 0.1 ml I.D route and neonate .05 ml.
 Protective value: 15-20 years.
 Efficacy: 0-80% vary region to region.
 Protect severity of childhood T.B., meningitis and milliary
57

58. • To date, Bacille Calmette Guerin (BCG) is the only licensed
vaccine against TB.
• First administered to humans in Paris in 1921.
• In India first intradermal BCG vaccine was administered in
Madanapalle, Andhra Pradesh in 1948.
• There are nearly 15 vaccine candidates in various phases
of clinical trials.
• The primary analysis included 14 studies and 3855
participants.
• Overall protective efficacy of 20%
• Restriction of the analysis to studies in which BCG
was administered at birth showed a protective efficacy
58

59. Boosting BCG with MVA85A
 Modified Vaccinia Ankara virus expressing antigen 85A
 Induces higher levels of both antigen specific CD4+ T and CD8+ T
cells when used together with BCG
 Phase I clinical trials showed excellent safety profile
 A randomised, placebo-controlled phase IIb trial in 2797 infants
revealed increased 17. 3% vaccine efficacy against Tuberculosis.
 MVA85A with BCG compare to alone BCG probably no effect on
the risk of developing active tuberculosis in trail 3 on 3187
participant.
 More adverse reaction at site of injection.
59

60. Cancer vaccine
 This is two type
1) Preventive( prophylactic )
2) Treatment (therapeutic vaccine )
 Preventive vaccine are gradsil, gradsil 9 and cervarix
for HPV type 16 and 18.
 Therapeutic vaccine strengthening the natural
defense system of body against the cancer. These
are provenge-R, CG0070 vaccine, Neuvax (E75)
60

61. Ca Prostate: PROVENGE®
(Sipuleucel-T)
 It is protein subunit vaccine approved by FDA on 29 April
2010.
 Autologous cellular immunotherapy
 Treatment of asymptomatic or minimally symptomatic
metastatic castrate resistant (mCRPC) prostate cancer or
androgen independent cancer .
 3 doses at 2-week intervals with I.V. route and median
survival 25.8 months in phase 3 Trial.
 Each dose contains minimum of 50 million autologous
CD54+cells activated with GM-CSF.
 Adverse events reported: chills, fatigue, fever, back pain,
nausea, joint ache, and headache.
 Treatment cost approved by FDA is 100,000 $.
61

62. Breast Cancer: Neuvax (E75)
 It is peptide derived from the extracellular domain of the HER2
protein.
 Two Phase II trials in 195 women with HER-2 positive breast cancer
showed a 75% reduction of relative risk of recurrence in 5 year.
 Phase III PRESENT trial (Prevention of Recurrence in Early-Stage
Node-Positive Breast Cancer with Low to Intermediate HER2
Expression with NeuVax™ Treatment) is ongoing.
 Two stages of administration:
 An intradermal injection once per month for six months (total 6)
 Booster shots once every 6 months for 30 months (total 5)
62

63.  It works on any residual cancer cells that express
HER2/neu associated tumors in breast, ovarian,
pancreatic ,colon, bladder and prostate.
63

64. Bladder cancer: CG0070 vaccine
 Type of Oncolytic virus therapy for BCG-Unresponsive Non-Muscle-
Invasive Bladder Cancer.
 Stimulates cytokine GM-CSF to enhance anti tumour immune
response
 Phase 1 study with Intravesical CG0070 demonstrated safety and
tumour response rate 48 – 77%
 Phase 2/3 pivotal BOND (Bladder Oncolytic virus for Nonmuscle
invasive bladder cancer Disease) trial of intravesical CG0070 for non-
muscle invasive bladder cancer patients is ongoing.
Burke JM et al. A first in human phase 1 study of CG0070, a GM-CSF
expressing oncolytic adenovirus, for the treatment of nonmuscle
64

65. Results from cancer vaccine trials
 Cancer vaccines have demonstrated minimal toxicity in all clinical
trials with little evidence of autoimmunity
 Patients who have received less prior chemotherapy are generally
more responsive to vaccines
 Technical and developmental challenges
 Challenges exist for developing combination therapy with cancer
vaccine and established cancer therapeutics.
Wolchok JD et al, Guidelines for the evaluation of immune
therapy activity in solid tumors: immune-related response criteria.
Clin Cancer Res, 2009
65

66. VACCINE AGAINST DIABETES
 It has been announced at the 75th Scientific Sessions of the
American Diabetes Association that the FDA will test the vaccine
on 150 people who are in an advanced stage of type I diabetes.
 A vaccine used over 100 years ago for tuberculosis (BCG) has
shown promise in reversing this disease.
 Patients with diabetes injected with the vaccine saw an increase in
the levels of a substance called tumor necrosis factor. The
increased level of TNF in the system destroys the T cells that are
hindering the production of insulin.
66

67.  In the phase I (preliminary) trial, a statistically
significant response to BCG has been demonstrated.
 There’s a new trial coming which will use the same
format as the previous one, on people at the age
between 18 and 60. The subjects will be injected with
the vaccine twice in a period of 4 weeks, and then
once a year for a 4-year time span.
67

68. Diamyd : A Diabetes Vaccine
 Diamyd, a vaccine to prevent diabetes, It is intended for the
treatment of children and adolescents with recent-onset type 1
diabetes. undergoing Phase III clinical trials in Europe
 91 0ut of 106 patients with type 1 diabetes are included phase 2b
trial DIAGNODE-2, in which Diamyd given directly lymph node to
preserve endogenous insulin production.
 Phase 3 in Europe and USA 320 participants suggest diamyd
failed to preserved beta cell function after 15 month.
 Dosage : 3 time one month apart combination with oral vit-D.
 Fallow up patient at 15 month to evaluate insulin production
capacity.
68

69. Nona particle vaccine: diabetes vaccine
 Developed by University of Calgary, Canada.
 It is successfully work on mice.
 Vaccine has nona-particle armed antigen that
stimulate body regulatory T cell which helps to
police killer T cells and prevent the response of
killer T cell.
 April 2010 license to develop vaccine is held by
Parvus Theraputics, University of Calgary.
 This vaccine is in phase 1 trial. 69

70. DNA Vaccines
 DNA vaccines are third generation vaccines
 DNA vaccine is DNA sequence used as a vaccine
 This DNA Sequence code for antigenic protein of
pathogen
 As this DNA inserted into cells it is translated to form
antigenic protein. As this protein is foreign to cells, so
immune response raised against this protein
 In this way ,DNA vaccine provide immunity against that
pathogen 70

71. Advantages of DNA Vaccines
 Cheaper and easier to produce
 No need to handle infectious pathogens during
production
 Can elicit both humoral & cell mediated immunity
 Stable at a broad range of temperature (no cold-chain
requirement)
 Can be designed and produced by genetic engineering
to have only the desired antigens or antigenic
sequences (epitopes) in the vaccine
71

72. Current Clinical Trials & Results
 June 2006,DNA vaccine examined on horse. Horse
acquired immunity against west nile viruses.
 August 2007,DNA vaccination against Multiple
Sclerosis was reported as being effective.
 DNA vaccines are in their early phase.
 There are no DNA vaccines in market at present. But
this is just the beginning. DNA vaccines are going to be
the vaccines of next generation.
72

73. LIFESTYLE VACCINES
NicVAX (Nicotine Conjugate Vaccine)
 Intended to reduce or eliminate physical dependence of
nicotine.
 Consist of hapten 3’-aminomethyline nicotine has been
conjugated to Pseudomonas aeruginosa exoprotein A.
 It stimulate immune system to produce antibodies that bind
nicotine to cross BBB to entering the brain.
 recent study showed decreased subject cravings for cigarettes.
 Trail 1 results: cut 65% cut by nicotine level in brain.
 Phase 2 trial results : continues abstinence between 19-26 week
on 3 dosages 3 month apart.
 Phase 3 trial is ongoing. 73

74. EDIBLE VACCINES
 It refer to any food typically plant, that produced
vitamin, protiens or other nourishment that act as a
vaccine against certain disease.
 EV has been discovered against rabies, cholera ,foot
and mouth disease, hepatitis B &C and hemorrhagic
fever.
 It is cheaper, needle free , easy to produce, safe,
purify, sterilize and distribute.
 Do not require sterilized production facilities and bio-
saftey standards and cold chain facility.
 Ex: BANANA , POTATO, TOMATO Used in tropical
countries as weaning foods
74

75. Some Edible Vaccine
75

76. Newer Technologies Of Vaccine Delivery
76

77. This technique is used for neurological disorder as Alzheimer's
disease, cerebro-vascular disease, Parkinson's, epilepsy,
multiple sclerosis, brain tumors and swine flu to bypass first
pass metabolism and blood brain barrier to increase
bioavailability of drugs or vaccine. 77

78. TCI produced mucosal and humoral/cellular response. Its has
vaccine enhancement patch(VEP) or needle free vaccine
delivery patch(VPD). Ex: influenza vaccine patch, anthrax, E.
coli( traveler’s diarrhea). these vaccine patch are in phase 2
78

79. it pierce only 15 micro meter of stratum corneum. Needle
is coated with antigen to produced sufficient immune
response.
example : anthrax, influenza, hepatitis B DNA vaccine. 79

80. Most widely use method. Deliver antigen into dermis.
Produced stronger immune response with lower antigen dose
as compare to S.C. or I.M.
Ex : Cancer vaccine( in phase 2), Hepatitis B. and Soluvia
(for seasonal influenza) is used by prefilled micro-injection.
80

81. jet injection device delivered vaccine formulated as dry
powder or liquid jet injection.
In dry powder/liquid jet injection penetrate to
epidermis/dermis without needle by releasing helium at 40
bar pressure.
81

82. 82