future generation vaccine in india

1. Future Generation Vaccines
PG Student : Dr.Santosh Kadle
PG Teachers: Dr. Lalit Sankhe
Dr. Amit Mohite
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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2.  Contents of seminar :
Future generation vaccines
Need of new vaccines
Current scenario for development of newer
vaccines
Technology transformation from inoculation to
recombinant technology.
Funding agencies
Timeline for newer vaccines in market.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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3. Why we need newer vaccines?
• Universal immunization against certain diseases has led to the eradication of smallpox
and almost completely eliminated infectious agents .But in developing countries , still it
is problem.
• The previous century’s successes in reducing the primary causes of mortality in
childhood to achieving Millennium developmental Goal-4.
• But to succeed in current and future , adequately targeted vaccines against the three
biggest killers— human immunodeficiency virus (HIV) infection, tuberculosis, and
malaria— are required to achieve a similar outcome.
• In numbers, Acquired immune deficiency syndrome (AIDS), malaria and tuberculosis
collectively cause more than five million deaths per year.
• In addition, some common vaccine-preventable diseases such as influenza and pertussis
continue to cause significant morbidity and mortality due to insufficient utilization of
vaccines.
• The new goals and with the trend of therapeutic vaccines moving toward targeting
morbidity rather than mortality.
• .
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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4. They benefit not only individual but also communities & even entire
population(e.g. eradication of small pox , elimination of poliomyelitis)
Impact of vaccine on communities &population are more rapid than that of many
other health intervention.
Cost effectiveness of vaccines – is another important factor in development of
vaccines . Because its cost is very much less than the cost due to disease burden
and helps in development by preventing loss of money and life years of peoples.
Coping with newer diseases like H1N1,Ebola and so on.. As there are new diseases
are coming with high mortality and pandemic nature , newer vaccine development must
be require.
16/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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5. 30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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6.  Vaccines currently in use
Live attenuated Killed organism Toxoid/protein Polysaccharide Glyco-conjugate Recombinant
• BCG • Typhoid • Diphtheria Pneumococcus Hib HBV
• Yellow fever • Cholera • Tetanus meningococcus Pneumococcus Lyme disease
• Polio (OPV) • Plague • Acellular Pertussis Hib MenACWY Cholera Toxin B
• Measles • Pertussis • Anthrax Typhoid (Vi) HPV
• Mumps • Influenza • Influenza subunit
• Rubella • Typhus
• Typhoid • Polio (IPV)
• Varicella • Rabies
• Rotavirus • JE
• Cholera • TBE
• Cold adapted
influenza
• HAV
• Rotavirus
reassortants
• Zoster
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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7.  Future generation vaccine
 Vaccines against HIV
 Vaccines against TB
 Vaccines against Malaria
Vaccines against Dengue
 Vaccines against Cancer
 Vaccines against Rotavirus
 Vaccines against JE
 Vaccines against TBE
 Vaccines against Influenza
 Vaccines against H1N1
 Vaccines against Ebola………..
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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8.  HIV Vaccine :
 Need of vaccine :
• To attain MDG -6
• Target 6. A: have halted by 2015 and begun to reverse the spread of HIV/AIDS.
• Target 6. B: achieve, by 2010, universal access to treatment for HIV/AIDS for all
those who need it.
• India has the third largest HIV epidemic in the world.
• In 2013, HIV prevalence in India was an estimated 0.3 percent. but because of
India's huge population (1.2 billion) this equates to 2.1 million people living with
HIV.
• In the same year, an estimated 130,000 people died from AIDS-related illnesses.
• To achieve control of HIV spread and strive for the achievement of zero new
infections, zero deaths due to AIDS and zero discrimination, there is need of
vaccine.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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9.  HIV Vaccine :
Development of vaccine :
• AIDS vaccine development is complex because HIV mutates rapidly, and its outer
spike protein conceals itself from the immune system.
• More recently, many scientists believe that an AIDS vaccine candidate will provide
robust protection against HIV infection only if it engages both arms of the
adaptive immune system, i.e. cell-mediated and antibody-based immune
responses.
• HIV vaccine development is complicated by the incredible variability of the virus,
and in particular its envelope protein .[gp 120 protein, gp 160 protein]
The role of WHO:
• The Initiative for Vaccine Research (IVR) works through the joint WHO-UNAIDS
HIV Vaccine Initiative to accelerate the availability of a safe, effective and
affordable HIV vaccine.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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10.  HIV Vaccine :
 Clinical trials :
• The first HIV vaccine trial to show a positive protective signal were released in 2009.
• The trial, termed RV 144, was performed in Thailand.
• It used a combination of two vaccines in a heterologous prime-boost paradigm, (i.e.
one vaccine given in four doses was then "boosted" by two doses containing both
vaccines.)
• Analysis of the trial showed that the group receiving the vaccine had an
infection rate 31.2% lower than the group that received the placebo.
• Although this result is not enough to qualify the vaccine for licensure, RV144 has
provided very useful pointers for a way forward.
• If the required efficacy can be shown in any of the trials, an HIV/AIDS vaccine could
become available from 2020.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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11.  Vaccine against Tuberculosis :
 Need of vaccine :
• Tuberculosis (Tb) continues to be a dreadful infection worldwide with nearly
1.5 million deaths in 2013.
• To achieve the Millennium Development goal of elimination of TB by 2050
will not be achieved without an effective new vaccine.
• Introduction of new and more efficacious vaccines would be required for a
95% reduction in Tb mortality and a 90% reduction in Tb incidence by 2035.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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12.  Vaccine against Tuberculosis :
Development of vaccine :
• To date, Bacille Calmette Guerin (BCG) is the only licensed vaccine against TB.
• There are nearly 15 vaccine candidates in various phases of clinical trials.
• It includes-
- five protein or adjuvant vaccines,
- four viral-vectored vaccines,
- three mycobacterial whole cell or extract vaccines,- M.vaccae vaccine
- one recombinant live – VPM 1002
- one attenuated - Mycobacterium tuberculosis (MTBVAC) vaccine.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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13. 30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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14. 30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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15.  Malaria Vaccine :
 Need of vaccine :
• According to WHO’s 2014 World Malaria Report there were an estimated 198 million
cases of malaria worldwide in 2013, occurring in around half of the world’s countries.
• These infections resulted in some 584 000 deaths , principally associated with
Plasmodium falciparum infection, of which 90% occurred in equatorial Africa.
• Most distressingly, malaria mortality is concentrated in children, with about 453 000
deaths of children aged younger than 5 years in 2013, the vast majority in African
countries.
• Infections by Plasmodium vivax and other parasites also cause a very substantial
burden of disease.
• Reducing the heavy burden of malaria, and its damaging effects on the health and
prosperity of people in developing countries, is one of the 21st century’s most
important health aspirations.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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16.  Malaria Vaccine :
Development of vaccine :
• In late 2012, the World Health Organization (WHO) published an update of the
“Rainbow Tables ,” which identified more than two dozen active malaria
vaccine candidates in clinical development(human testing) and more than a
dozen in preclinical development.
• The vast majority of candidates in clinical development targeted Plasmodium
falciparum, with roughly equal numbers targeting the blood and pre-
erythrocytic stages of the malaria parasite.
• The Rainbow Tables reported only one vaccine candidate in large-scale, late-
stage testing ,namely the RTS,S candidate under development by Glaxo Smith
Kline Vaccines (GSK), the PATH Malaria Vaccine Initiative (MVI), and research
Centers in seven African countries
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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17.  Malaria Vaccine :
Clinical trials :
• The malaria vaccine candidate RTS,S/AS 01
• RTS,S/AS 01 is the most advanced vaccine candidate against the most deadly form
of human malaria, Plasmodium falciparum.
• A Phase III trial began in May 2009 and completed enrolment with 15 460 children
in the following seven countries in sub-Saharan Africa: Burkina Faso, Gabon,
Ghana, Kenya, Malawi, Mozambique, and the United Republic of Tanzania.
• There are two groups in the trial:
1]children aged 5-17 months at first dose receiving only the RTS,S/AS 01 vaccine
2] children aged 6-14 weeks at first dose who receive the same malaria vaccine in
co-administration with pentavalent vaccines in the routine immunization schedule.
• Vaccine could be available from late 2015 [Recent news- Mosquirix vaccine is
approved for use in Africa.]
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
17

18. Mechanism of action of RTS,S/As 01 :
Block progression to red blood cells and clinical malaria
To evoke an immune response to prevent hepatocyte infection,
Combined with elements designed
Epitopes from the parasite circum-sporozoite protein
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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19.  Malaria Vaccine :
Types of malaria vaccines
• Early malaria vaccine development efforts focused on the parasite's pre-
erythrocyticstage—the period during which the organism, in the form of
a sporozoite, enters a person's blood stream and heads for the liver, where it
matures and begins a prolific multiplication process.
• Today, vaccine developers are trying to develop three types of vaccines:
1] Pre-erythrocytic vaccine candidates
2] Blood-stage vaccine candidates
3] Transmission-blocking vaccine candidates
 The role of WHO:
• WHO- Initiative for Vaccine Research (IVR) with collaboration with PATH-
Malaria Vaccine Initiative (MVI )to accelerate the availability of a safe, effective
and affordable Malaria vaccine
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
19

20.  Dengue Vaccine :
 Need of vaccine :
• The disease is caused by four closely related viruses, the Dengue viruses 1-4.
• One recent estimate indicates 390 million dengue infections per year ,of which 96
million manifest clinically (with any severity of disease).
• Another study, of the prevalence of dengue, estimates that 3900 million people, in
128 countries, are at risk of infection with dengue viruses.
• An estimated 500 000 people with severe dengue require hospitalization each year &
About 2.5% of those affected die.
• There are no specific dengue therapeutics and prevention is currently limited to
vector control measures. A dengue vaccine would therefore represent a major
advance in the control of the disease.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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21.  Dengue Vaccine :
 Development of vaccine :
• The growing global epidemic of dengue is of mounting concern, and a safe and
effective vaccine is urgently needed.
• WHO expects vaccines to be an integrated part of the Global dengue prevention
and control strategy (2012-2020).
• While no licensed dengue vaccine is available, several vaccine candidates are
currently being evaluated in clinical studies.
• Due to dengue-type specific complexities, vaccine development focuses on
the generation of a tetravalent vaccine aimed at providing long-term protection
against all virus serotypes.
• Additional challenges are posed by the lack of an adequate animal disease
model and the resulting uncertainty around correlates of protection
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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22.  Dengue Vaccine :
Clinical trials :
• Three tetravalent live-attenuated vaccines are under development in phase II
and phase III clinical trials, and 3 other vaccine candidates (based on subunit,
DNA and purified inactivated virus platforms) are at earlier stages of clinical
development.
• a live-attenuated tetravalent vaccine based on chimeric yellow fever-dengue
virus (CYD-TDV), has progressed to phase III efficacy studies.
• Vaccine could be available from 2016 .
 The role of WHO:
• The Initiative for Vaccine Research (IVR) as a part of Dengue Vaccine Initiative
(DVI )to accelerate the availability of a safe, effective and affordable Dengue
vaccine
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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23. 30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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Image courtesy from Dengue vaccine initiative : downloaded from http://www.denguevaccines.org/

24.  Meningococcal Vaccine :
 Need of vaccine :
• Neisseria meningitides is the one with the potential to cause large epidemics.
• Twelve sero-groups of Neisseria meningitides have been identified, six of which
(A, B, C, W135, X and Y) can cause epidemics.
• The highest disease burden is reported from sub-Saharan Africa where for over
a century, major meningococcal meningitis epidemics have occurred every 10–12
years in the African meningitis belt, a savannah region extending from Senegal to
Ethiopia.
• The majority of these epidemics are caused by group A and incidence rates can
be as high as 500 cases per 100 000 population, affecting primarily the under 30
age group.
• While group A predominates through Africa and Asia, groups B and C are
responsible for the majority of cases in Europe, the Americas, Australia and New
Zealand.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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25. Meningococcal Vaccine :
 Development of vaccine :
• Meningococcal polysaccharide vaccines have been used to control the disease
for over 30 years.
• They are available in either bivalent (groups A and C), trivalent (groups A, C and
W), or tetravalent (groups A, C, Y and W135) forms.
• For group B, however, polysaccharide vaccines cannot be developed due to
antigenic mimicry with the meningococcal B polysaccharide in human neurologic
tissues. Consequently, vaccines against B used in particular in Cuba, New
Zealand and Norway have been outer membrane proteins and strain-specific,
tailored to control epidemics caused by a particular strain. Promising
meningococcal group B protein vaccines are in late stages of development.
• Meningococcal conjugate vaccines against group C have been widely used to
control the disease since 1999. Tetravalent A, C, Y and W135 conjugate vaccines
have been licensed since 2005 for use in children and adults in Canada, the
United States of America, and Europe.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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26.  Meningococcal Vaccine :
Meningitis Vaccine Project (MVP) :
• Meningitis Vaccine Project (MVP) was started as a partnership between
PATH and WHO, funded by a Bill & Melinda Gates Foundation grant in 2001
.
• The first meningococcal A conjugate vaccine, MenAfriVac, developed
through the Meningitis Vaccine Project
• It was introduced nationwide in Burkina Faso, and in selected areas of Mali
and Niger in December 2010, through mass vaccination campaigns among 1
to 29 year-olds.
• Subsequently, by the end of the 2011 meningitis season, these countries
reported the lowest number of confirmed meningitis A cases ever recorded
during an epidemic season.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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27.  Meningococcal Vaccine :
Clinical trials:
• Related to licensing and prequalification of MenAfriVac for use in 1 to 29 year-
olds have been successfully completed in India, Mali, Senegal, and the Gambia.
• A Phase II trial to evaluate the immunogenicity and safety of the vaccine in
infants in Ghana is scheduled for completion in 2012.
• A Phase III clinical study, expected to start in Mali in early 2012 will provide the
complementary data to support a policy recommendation for a paediatric
indication by 2014.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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28.  Ebola Virus Vaccine :
 Need of vaccine :
• In 2014,there was epidemic of Ebola virus disease in West African countries
Guinea , Sierra Leone and Liberia , also some cases in Nigeria.
• WHO declared world-wide emergency for Ebola virus disease
• Mortality rate was about 80 % to 90 % in affected cases.
• About more than 27678 cases and 11276 people died in this emergency.
• But to response to diseases like Ebola Virus Disease in future , there should be
vaccine development to prevent mortality.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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29.  Ebola Virus Vaccine :
 Development of vaccine :
• VSV-EBOV was developed by the Public Health Agency of Canada.
• The vaccine was licenced to New Link Genetics, and on November 24, 2014,
New Link Genetics and Merck announced their collaboration on the vaccine.
• GlaxoSmithKline (GSK) developed the cAd3-ZEBOV vaccine in collaboration with
the United States National Institutes for Health.
• Ring vaccination was selected, with a design allowing part of the rings (contacts
of the newly diagnosed Ebola case) to be vaccinated immediately after the case
is detected, while other rings will be vaccinated 3 weeks later (delayed ring).
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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30.  Hepatitis E Vaccine :
 Need of vaccine :
• Hepatitis E is a viral liver infection which is usually self-limiting, but may develop
into fulminant hepatitis (acute liver failure).
• Annually, there are an estimated 20 million hepatitis E infections, over 3 million
acute cases of hepatitis E, and over 57,000 hepatitis E-related deaths.
• Hepatitis E virus is transmitted mainly via the faecal/oral route through ingestion
of contaminated drinking water.
• Other, less common, transmission routes have been identified including through
ingestion of food products derived from infected animals and shellfish; transfusion
of infected blood products; and vertical transmission in pregnancy.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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31.  Hepatitis E Vaccine :
Development of vaccine :
• Recombinant HEV vaccine (HEV 239):
--It was developed in China and was approved in June 2012.
--3 doses (30 ug of purified recombinant hepatitis E antigen per dose)
of HEV 239
-- administered at months 0, 1 and 6 resulted in 100% efficacy at 1
year in a Chinese study
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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32.  Rota virus Vaccine :
 Need of vaccine :
• Rotaviruses are the most common cause of severe diarrhoeal disease in young
children throughout the world.
• According to WHO 2008 estimates, about 450 000 children aged <5 years die each
year from vaccine-preventable rotavirus infections; the vast majority of these
children live in low-income countries.
Development of vaccine :
Two oral, live, attenuated rotavirus vaccines,
1] Rotarix™ (derived from a single common strain of human rotavirus)
2] RotaTeq™ (a reassorted bovine-human rotavirus), are available internationally
and WHO prequalified; and both vaccines are considered highly effective in
preventing severe gastrointestinal disease.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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33.  JE Vaccine :
 Need of vaccine:
• Japanese encephalitis (JE) is the main cause of viral encephalitis in many
countries of Asia.
• The case fatality rate can be as high as 30% among those with disease symptoms;
20-30% of those who survive suffer permanent neuropsychiatric sequelae.
• In areas where the JE virus is common, encephalitis occurs mainly in young
children because older children and adults have already been infected and are
immune.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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34.  JE Vaccine :
 vaccine:
• There are four main types of JE vaccines currently in use:
1] inactivated mouse brain-based vaccines,
2] inactivated cell-based vaccines,
3] live attenuated vaccines , SA 14-14-2
4] live recombinant vaccines.
• JE vaccination should be integrated into national immunization schedules in all
areas where JE is recognized as a public health priority.[ Karnataka , West
Bengal, Uttar Pradesh & Assam.]
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
40

35.  Tick Borne Encephalitis Vaccine :
 Need of Vaccine:
• Tick-borne encephalitis is an important cause of viral infections of the central
nervous system in eastern, central and northern European countries, and in
northern China, Mongolia, and the Russian Federation.
• Approximately 10 000–12 000 clinical cases of tick-borne encephalitis are
reported each year, but this figure is believed to be significantly lower than the
actual total.
• Immunization offers the most effective protection.
Vaccines :
• Currently, there are four widely used vaccines of assured quality:
• FSME- Immun and Encepur, manufactured in Austria and Germany respectively,
and based on European strains of the virus;
• TBE-Moscow and EnceVir, manufactured in the Russian Federation and based on
Far-Eastern strains.
• The four vaccines are considered to be safe and efficacious.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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36.  Tick Borne Encephalitis Vaccine :
Recommendations of WHO:
• In areas where the disease is highly endemic (i.e. where the average pre-
vaccination incidence of clinical disease is ≥5 cases/100 000 population per year),
implying that there is a high individual risk of infection, WHO recommends that
vaccination be offered to all age groups, including children.
• Where the pre-vaccination incidence of the disease is moderate or low (that is, the
annual average during a 5-year period is <5/100 000) or is limited to particular
geographical locations or certain outdoor activities, immunization should target
individuals in the most severely affected cohorts.
• People travelling from non-endemic areas to endemic areas should be offered
vaccination if their visits will include extensive outdoor activities.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
42

37.  Yellow fever Vaccine :
 Need of vaccine :
• Yellow Fever (YF) is a mosquito-borne viral disease of humans and other
primates, and is currently endemic in over 43 countries in the tropical regions of
Africa and The Americas.
• Infection with the YF virus can be asymptomatic or cause a wide spectrum of
disease, from mild symptoms to severe illness with bleeding, jaundice and,
ultimately, death.
• Over 30,000 deaths occur each year and this figure would be much higher
without vaccination.
• Aedes aegypti, is the most important vector. Transmission is complex with
different characteristics in different endemic areas.
• All currently available yellow fever vaccines are live, attenuated and based on
the 17D attenuation variant.
• Vaccines from four manufacturers are currently prequalified by WHO.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
43

38.  Yellow fever Vaccine :
 vaccine :
• All currently available yellow fever vaccines are live, attenuated and based on
the 17D attenuation variant.
• Vaccines from four manufacturers are currently prequalified by WHO.
• A single dose of YF vaccine is sufficient to confer sustained life-long protective
immunity against YF disease.
• In view of the ongoing transmission of YF virus, and the proven efficacy and
safety of YF vaccination, WHO recommends that all endemic countries should
introduce YF vaccine into their routine immunization programmes.
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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39. References:-
1. State of the worlds vaccines and immunization, third ed. Geneva, World Health Organization,2009
2. Vaccines & Biologicals ,Annual Report 2000, Department of Vaccines &Biologicals , Geneva, World
Health Organization,2001
3. Jonathan A. Advances in vaccine Technology and their impact on managed care ,Vaccine journal ,
Volume 33 -1 January 2008 page 35-41
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http://www.who.int/immunization/research/development/hiv_vaccdev/en/
, accessed on 20 June 2015
5. World Health Organization. Development of Malaria vaccines . Available from:
http://www.who.int/immunization/research/development/malaria_vaccdev/en/
, accessed on 20 June 2015
6. Ahsan M., Recent advances in the development of vaccines for tuberculosis , Journal of Therapeutic
Advances in Vaccines-2015, Downloaded from :http://www.tav.sagepub.com on July 20, 2015
7. PATH, Malaria Vaccine Development Initiative Malaria ,Vaccine Development Update Fact sheet
downloaded from :http:// www.path.org.www.malariavaccine.org
30/07/2015
Department of Community Medicine, Grant Medical College
,Mumbai
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40. References:-
10. Malaria Vaccine Development Initiative, Development of Malaria Vaccine
downloaded from :http:// www.malariavaccine.org on July 20 , 2015
11. Asha N Shah. Guidelines from IAP, Immunology section 14 ,Chapter no.101 on Adult Immunization
12. World Health Organization. Development of Tuberculosis vaccines . Available from:
http://www.who.int/immunization/research/development/tb_vaccdev/en/
, accessed on 20 June 2015
13. World Health Organization. Global strategy for Dengue prevention and control 2012-2020
, Geneva,WHO,2012.Available from http://www.who.int/immunization/reasesrch/develpoment
, accessed on 20 June 2015.
14. Kyogo I. et al . Recent Advances in Cancer Vaccines: An Overview Japanese Journal of Clinical
Oncology 2009;39(2)73–80 doi:10.1093/ jjco /hyn132. Downloaded from
:http://ijco.oxford.djournal.org. on 20 June 2015
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,Mumbai
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41. Thank you !!
30/07/2015
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,Mumbai
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