future generation vaccines

Department of Community Medicine, Grant Medical College ,Mumbai

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Future Generation Vaccines PG Student : Dr.Santosh Kadle PG Teachers: Dr. Lalit Sankhe

Dr. Amit Mohite

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Contents of seminar :Future generation vaccinesNeed of new vaccinesCurrent scenario for development of newer

vaccinesTechnology transformation from inoculation to

recombinant technology.Funding agenciesTimeline for newer vaccines in market.

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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.

• .

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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.

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Vaccines currently in useLive 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

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Future generation vaccine Vaccines against HIV Vaccines against TB Vaccines against MalariaVaccines against Dengue Vaccines against Cancer Vaccines against Rotavirus Vaccines against JE Vaccines against TBE Vaccines against Influenza Vaccines against H1N1 Vaccines against Ebola………..

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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.

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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.

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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.

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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.

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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.

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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.

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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 preerythrocytic 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

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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.]

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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

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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

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http://www.malariavaccine.org/malvac-glossary.php#preerythrocytic

http://www.malariavaccine.org/malvac-glossary.php#preerythrocytic

http://www.malariavaccine.org/malvac-glossary.php#sporozoite


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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.

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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

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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

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Image courtesy from Dengue vaccine initiative : downloaded from http://www.denguevaccines.org/

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.

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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.

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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.

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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.

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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.

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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).

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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.

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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

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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


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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.

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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.]

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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.

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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.

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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.

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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.

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References:-1. State of the worlds vaccines and immunization, third ed. Geneva, World Health Organization,20092. Vaccines & Biologicals ,Annual Report 2000, Department of Vaccines &Biologicals , Geneva, World

Health Organization,20013. Jonathan A. Advances in vaccine Technology and their impact on managed care ,Vaccine journal ,

Volume 33 -1 January 2008 page 35-414. World Health Organization. Development of HIV vaccines . Available from: http://www.who.int/immunization/research/development/hiv_vaccdev/en/ , accessed on 20 June 20155. World Health Organization. Development of Malaria vaccines . Available from: http://www.who.int/immunization/research/development/malaria_vaccdev/en/ , accessed on 20 June 20156. 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, 20157. PATH, Malaria Vaccine Development Initiative Malaria ,Vaccine Development Update Fact sheet downloaded from :http:// www.path.org.www.malariavaccine.org

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References:-10. Malaria Vaccine Development Initiative, Development of Malaria Vaccine downloaded from :http:// www.malariavaccine.org on July 20 , 201511. 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 201513. 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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Thank you !!

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future generation vaccines

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