NEWER VACCINES

Presenter – Pramod Kumar SahModerator – Dr. Subodh S. Gupta

"With the exception of safe water, no other modality, not even antibiotics, has had such a major effect on mortality reduction…"

FRAMEWORK

Introduction Vaccine Development of vaccines Need for new vaccines Regulation & testing of vaccines Newer / Improved vaccines Vaccine on clinical trial

VACCINE

It is a suspension of attenuated or killed microorganisms, or of antigenic proteins derived from them, administered for prevention or amelioration of infectious diseases.

Helps stimulate the body's own immune system to produce antibodies to fight particular disease.

Vaccine may contain live but avirulent organism, or killed microorganism , or purified macromolecular component of a microorganism or a plasmid that contains a complementary DNA encoding a microbial antigens. Antibodies that are produced to protect against future infection.

Type of Vaccine Disease

Live, attenuated vaccine Measles, mumps, rubella, polio (Sabin vaccine), yellow fever

Inactivated or “killed” vaccine

Cholera, flu, hepatitis A, Japanese encephalitis, plague, polio (Salk vaccine), rabies

Toxoid vaccine Diphtheria, tetanus

Subunit vaccines Hepatitis B, pertussis, pneumonia caused by Streptococcus pneumoniae

Conjugate vaccines Haemophilus Influenza type B, pneumonia caused by Streptococcus pneumoniae

DNA vaccines In clinical testing

Recombinant vector vaccines In clinical testing

THE DEVELOPMENT OF VACCINES

First generation—whole - organism vaccines - Inactivated/Killed,

-live attenuated Second generation

subunit vaccine, recombinant antigen Vaccine,, synthetic peptide vaccines

Third generation----DNA vaccine

YEAR MILESTONES1796, Inoculation of pus from the hand of a milkmaid with cowpox

1881 First vaccine against rabies,

1896 Vaccine for cholera and typhoid

1897 Plague vaccine

1923 Use of diphtheria "toxoid" to kill bacteria. 1926 A killed vaccine for pertussis ("whooping cough")

1927 A tetanus "toxoid" is developed.

1954 Jonas Salk develops a killed polio virus vaccine1961 Alfred Sabin develops an oral polio vaccine using a live virus1963 Measles vaccine1964 A killed rabies vaccine1967 Mumps1970s Meningoccocal, pneumococcal and haemophilus influenza type b (Hib) vaccines are developed,

1986 A vaccine for Hepatitis B is licensed with an antigen that is cloned rather than grown. 1990 A killed vaccine for hepatitis A is developed1995 A varicella (chicken pox) vaccine is licensed for use in children2005-6 RotaTeq vaccine

2003 1st Vaccine for Influenza

2006 1st vaccine for HPV

2009 Swine flu vaccine

2011 Pentavac vaccines

NEED FOR NEW VACCINES

Pathogens that have circulated for long but existence ignored : HepB, Pneumococcal diseases, Rota - virus 

Old pathogens change geographical habitat and are introduced into newer areas : Chikungunya, West Nile

New pathogens have emerged : SARS, Avian Flu

Pathogens thought to be controlled have re-emerged : M tuberculosis

FRAMEWORK FOR DECISION MAKING ON INTRODUCING NEW VACCINES

Is the disease a public health problem? Is immunization the best control strategy for this disease? Is the immunization programme working well enough to add a vaccine? What would be the net impact of the vaccine? Is the vaccine a good investment? How will be the vaccine funded? How will the addition of the new vaccine be implemented?

REGULATION & TESTING OF VACCINES

Phase I: is a human trial & focuses on safety involving small groups.

Phase II: Involves moderate-sized "target" populations to determine both safety and the stimulation of immune response

Phase III: extensive testing performed on large target populations to establish whether a vaccine actually prevents a disease as intended (efficacy)

GENERAL WHO POSITION ON NEW VACCINESVaccines for large-scale public health use should: meet the quality requirements as defined in the Global Programme on

Vaccines policy statement on vaccine quality be safe and have a significant impact against the actual disease in all

target populations if intended for infants or young children, be easily adapted to schedules

and timing of the national childhood immunization programmes not interfere significantly with the immune response to other vaccines

given simultaneously be formulated to meet common technical limitations, e.g. in terms of

refrigeration and storage capacity be appropriately priced for different markets.

NEWER VACCINES

LICENSED VACCINES THAT ARE NOT BEING USED WIDELY

New/Improved: Hib: PRP-conjugates Pneumococcus: PS-conjugates Cholera: inactivated Rotavirus: live, attenuated Typhoid: Vi, Ty2la HAV: Inactivated Group A Meningococcus: PS-conjugates Varicella: Live-attenuated Human papilioma virus Japanese Encephalitis

VACCINES ON CLINICAL TRIALS

1. Malaria2.Dengue4. HIV

HAEMOPHILLUS INFLUENZAE TYPE B (HIB)

Indications: Pneumonia, respiratory infection common in children < 2 years

Vaccine Conjugate polysaccharide b vaccine

Schedule: 6,10,14 weeks booster at 12-15 months

Unvaccinated children ≥ 7 months of age- 2 doses Unvaccinated children ≥ 15 months of age- 1 dose Unvaccinated children ≥ 5 yrs- only if underlying immune disorder or

asplenia

HIB VACCINES CONT…

Dose: 0.5 ml IM ant.lat.aspect of thigh

Contra-indictaions: Local pain, erythema, fever

Immunogenicity- More than 95% of infants- protective antibody levels after a primary series of two or three doses. Immunogenic in patients with increased risk for invasive disease, such as sickle-cell disease, leukemia, (HIV) infection, splenectomy.

Recently, quadruple vaccine (DPT+Hib) and pentavalent (DPT+Hib+HepB) available.

WHO POSITION

 Calls for the use of Hib vaccines in all infant immunization programs and

states that the vaccine is the only public health tool capable of preventing the majority of cases of serious Hib disease.

PNEUMOCOCCAL VACCINEA. Pneumococcal polysaccharide vaccine (PV23): 1977- purified cap.polysaccharide Ag from 14 strains(14-valent)

Indication: widely licensed for use in adults and children aged >2 years who have certain underlying medical conditions.(Sickle cell disease, damaged spleen / spleenectomised , AIDS, disease affecting immune system, diabetes, liver ds. chronic lung & heart disease, who is on immunosuppresive therapy).

B .Pneumococcal conjugated vaccine (PCV7): 2000Composition: Purified cap. Polysaccharide of 7 serotypes(PCV7) of

pneumococci (4, 9V, 14, 19F, 23F, 18C, 6B) conjugated to a non toxic variant of diptheria toxin (CRM197)

Indication : infants and toddlers (6 weeks to 9 years)

PNEUMOCOCCAL VACCINE CONT…. Dose: 0.5 ml Schedule – S/C or IM

<6 months 3 doses (6, 10, 14wks) 7-11 months- 2 doses & booster after 1yr 12-23 months-2 doses >24mnths single dose

Not recommended for >59 months of age

No revaccination recommended

Side-effects: Redness, tenderness, swelling ,fever, loss of appetite, irritability, drowsiness

Contraindications: Allergic reaction to 1st dose, Severely ill Efficacy of upto 57 % for cases of otitis media by serotypes represented in the vaccine is

reported.

PNEUMOCOCCAL VACCINE CONT… The Gambia Pneumococcal Vaccine Trial:

A Phase III trial of the vaccine involving 40 000 people was completed in South Africa in 2002, and

Phase III trial with 17 437 subjects was concluded in the Gambia in 2004 9-valent vaccine (PCV7+ 1 & 5) 77% effective in preventing pneumococcal infections 16% decrease in child mortality

New 10-valent pneumococcal vaccine:

“Synflorix” developed by GSK Additional 3 serotypes to PCV7- 1, 5, 7F Conjugated to protein D of Non Typable H.Influenza (NTHi) GSK received European Commission authorisation on 31st March 2009

PNEUMOCOCCAL VACCINE - INDIA

Actual burden of pneumococcal disease in India- not known.

Currently available seven-valent conjugate vaccine (PCV-7) covers strains

attributable to approximately 50% burden of S. pneumoniae in India.

The steps needed for inclusion of these vaccines in UIP:

The burden of disease studies for S. pneumoniae Evidence generation and cost effective analysis studies for vaccine The support and advocacy for vaccine research to incorporate

strains which are prevalent in India The preparation of a decision making tool to introduce new vaccines

in UIP.

WHO POSITION WHO considers that pneumococcal conjugate vaccine should be a

priority for inclusion in national childhood immunization programmes. Countries with mortality among

children aged <5 years of >50 deaths/1000 births or with more than 50 000 children’s deaths annually

should make the introduction of PCV-7 a high priority for their immunization programmes.

CHOLERA VACCINE:

Vaccine Killed whole-cell vaccine DUKORAL, 2004 (cholerae 01 in combination with recombinant B-sub unit of cholera toxin)

Indications/Age Travellers , Aid workers assisting in disaster relief or refugee camps, travelling to remote regions with limited access to medical care, risk travellers with underlying gastrointestinal illness or immune suppression >2yrs of age

Dose & route 2 doses orallySchedule 1wk apart

3 weeks before departureSide effects NoneContraindications Hypersensitivity to previous dose

Protection (85–90%) protection for 6 months after the second dose. Protection declines rapidly in young children after 6 months, but remains as high as 62% in adult vaccine recipients.

CHOLERA VACCINE:

Vaccine Shanchol and mORCVAXThe closely related bivalent oral cholera vaccines based on serogroups O1 and O139.

Indications/Age Above 1 years of age

Dose & route Orally, 2 doses

Schedule 2 liquid doses 14 days apart

Protection protective efficacy of the vaccine for all ages after 2 doses is 66%licensed in 2009 as mORCVAX in Viet Nam and as Shancholin India; mORCVAX is currently intended for domestic use in Viet Nam, whereas Shanchol will be producedfor Indian and international markets.

WHO POSITION Cholera control should be a priority in areas where the disease is

endemic. Given the availability of 2 oral cholera vaccines and data on

their efficacy, field effectiveness, feasibility and acceptance in cholera-affected populations,

immunization with these vaccines should be used in conjunction with other prevention and control strategies in areas where the disease is endemic and should be considered in areas at risk for outbreaks.

Rotavirus vaccine:

Vaccine Rotarix™ vaccine(The monovalent human ) 2007

RotaTeq™ vaccine(pentavalent bovine–human) 05-06

Indications/Age

Infants 2 and 4 months of age. Infants2, 4 and 6 months of age

Route Orally 2 doses Orally 3 dosesSchedule 1st dose at 6wks & 2nd at

16wks.Interval bet 2doses at least 4wks

1st dose at 6-12wks and 2nd,3rd doses at an interval of 4-10wks

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 AGE febrile illness

Hypersensitivity, history of intussusception or intestinal malformations AGE, febrile ill

ROTAVIRUS VACCINES: INDIA A vaccine based on Indian neonatal strains: clinical trials.

RotarixTM (GSK) -now available in India A monovalent attenuated human rotavirus vaccine Human rotavirus strain 89-12 grown in vero cells and contains the G1P1 [8] strain Lyophilized vaccine The vaccine and the diluents should be stored at 2 to 8° C and must not be frozen. Administer promptly after reconstitution as 1 ml orally.

The first dose can be administered at the age of 6 weeks (no later than at the age of 12 weeks.)

The interval between the 2 doses - at least 4 weeks. The 2-dose schedule should be completed by age 16 weeks, (no later than by 24 weeks of age.)

WHO POSITION

included in all national immunization programs, especially in countries with high death rates, such as those in South and South-eastern Asia and Sub- Saharan Africa.

the age restriction should be removed in countries where disease burden is high and delays in vaccinations and deaths from rotavirus are common.

low risk of intussusception from rotavirus vaccination (about 1 to 2 per 100,000 infants vaccinated),

TYPHOID VACCINES

Indications:1. Travelers going to endemic areas who will be staying for a

prolonged period of time,2. Persons with intimate exposure to a documented S. typhi

carrier 3. Microbiology laboratory technologists who work frequently

with S. typhi 4. Immigrants5. Military personnel

TYPHOID VACCINES

Two types:

1. Injectable Typhoid vaccine (TYPHIM –Vi,TYPHIVAX)

2. The live oral vaccine (TYPHORAL)

TYPHOID VACCINE CONT… Injectable Typhim –Vi

1. This single-dose injectable typhoid vaccine, from the bacterial capsule of S. typhi strain of Ty21a.

2. This vaccine is recommended for use in children over 2 years of age.

3. Sub-cutaneous or intramuscular injection4. Efficacy : 64% -72%

TYPHOID VACCINE CONT…Typhoral vaccine: 1. live-attenuated-bacteria vaccine manufactured from the Ty21a strain of

S. typhi. 2. The efficacy rate of the oral typhoid vaccine ranges from 50-80%3. Not recommended for use in children younger than 6 years of age. 4. The course consists of one capsule orally, taken an hour before food with

a glass of water or milk (1stday,3rd day &5th day)5. No antibiotic should be taken during this period6. Immunity starts 2-3 weeks after administration and lasts for 3 years7. A booster dose after 3 years

WHO POSITION Typhim –Vi and Typhoral vaccines provide appreciable levels of

protection and have a good record of safety, improved vaccines against typhoid fever are desirable.

vaccines should confer higher levels and more durable protective immunity in all age groups, including those aged <2 years, preferably without the need for booster doses.

HEPATITIS AType of vaccine Inactivated (killed)

Number of doses Two 0.5ml i.m. Second dose 6–24 months after the first

Booster May not be necessary

Contraindications Hypersensitivity to previous dose

Adverse reactions Mild local reaction of short duration, mild systemic reaction

Before departure Protection 2–4 weeks after first dose

Recommended All non-immune travellers to endemic areas

HEPATITIS A VACCINES: INDIA

India: > one billion population over-crowded living conditions and lack of proper sanitation and education, Hepatitis A continues to be a very frequent infection.

HAV infection produces lifelong immunity to hepatitis A, Based on recent studies (Pune, Mumbai, Delhi Chennai) children specially

from low socio-economic category continue to be almost universally exposed to HAV.

Thus, at present, Indian population does not qualify for immunization with hepatitis A vaccine.

WHO POSITION

Highly endemic countries: HAV infects virtually all young children, without causing symptoms but effectively protecting the population against symptomatic hepatitis A disease in later life. In such countries, large-scale hepatitis A vaccination is not required.

Intermediate endemic countries where a relatively large proportion of the adult population is susceptible to HAV, and where hepatitis A represents a significant public health burden, large-scale childhood vaccination may be considered as a supplement to health education and improved sanitation.

Low endemic countries: indicated for individuals with increased risk of contracting the infection.

HAV be integrated into the national immunization schedule for children aged ≥1 year if indicated on the basis of incidence of acute hepatitis A, change in the endemicity from high to intermediate, and consideration of cost effectiveness.

COMBINED HEPATITIS A AND HEPATITIS B VACCINE 2001- FDA

Twinrix (GlaxoSmithKline)

The vaccine is administered in a three-dose series at 0, 1, and 6 months

Twinrix is approved for persons aged ≥18 years with indications for both hepatitis A and hepatitis B vaccines.

MENINGOCOCCAL VACCINE:Indications: Travellers to industrialized countries are exposed to the possibility of sporadic

cases.

Outbreaks of meningococcal C disease occur in schools, colleges, military barracks and other places where large numbers of adolescents and young adults congregate.

Long-term travellers living in close contact with the indigenous population may be at greater risk of infection.

Vaccines: - Polysaccharide vaccine - Conjugate vaccine

CONTINUATION……………

Polysaccharide vaccines:bivalent (A and C) or tetravalent (A, C, Y and W-135)One dose, provides protection for 3–5 years Vaccine should be given 2 weeks before departureChildren under 2 years of age are not protected by the vaccineTravellers should opt (A, C, Y, W-135) than the bivalent vaccineConjugate vaccine:

Monovalent serogroup C conjugate vaccines licensed for use since 1999 incorporated in national vaccination programmes in an increasing number

of countries. prolonged duration of protection in infants who are vaccinated at 2, 3 and 4

months of age.

WHO POSITION

WHO recommends that countries with high (>10 cases/100 000 population/year) or intermediate endemic rates (2–10 cases/100 000 population/year) of

invasive meningococcal disease and countries with frequent epidemics

In these countries, the vaccine may be administered through routine immunization programmes, supplementary immunization activities (SIAs), during outbreaks, or through private vaccination services.

VARICELLA In several industrialized countries, Varicella vaccines have been

introduced into the childhood immunization programmes. Most adult travellers from temperate climates are immune (as a result of

either natural disease or immunization). Adult travellers without a history of Varicella who travel from tropical

countries to temperate climates may be at increased risk and should consider vaccination.

Use at 9 months of age and older. optimal age for Varicella vaccination is 12–24 months.

In Japan and several other countries 1 dose of the vaccine is considered sufficient regardless of age.

In the United States 2 doses 4–8 weeks apart, are recommended for adolescents and adults.

VARICELLA VACCINE CONT… Side effects: Mild Varicella-like disease with rash within 4 weeks. Contraindications Pregnancy (pregnancy should be avoided for 4 weeks following

vaccination), Ongoing severe illness Anaphylactic reactions Immuno suppression.

WHO POSITION These position papers are concerned primarily with the use of vaccines

in large-scale immunization programmes.

Limited vaccination for individual protection, as executed mostly in the private sector, may be a valuable supplement to the national programmes, but is not emphasized in this policy document.

MMR VARICELLA VACCINE (MMRV) Vaccination schedule and use- 12 months- 12 yrs of age 1st dose as early as possible after 12 months of age, 2nd after at least 3 months

interval Post-exposure prophylaxis within 3 days

Adverse reactions- Fever, measles like rash 5-12 days after vaccination, febrile seizures ( risk

higher than MMR and Varicella given separately)

Storage- Very fragile, -15°C Never at room temp.or refrigerator Diluent (sterile water) - refrigerator or room temp.

HUMAN PAPILLOMA VIRUS VACCINE

Vaccine Quadrivalent vaccine (2006)VLPs for 6,11,16,18

Bivalent vaccine (2007)VLPs for 16,18

Indications Young adolescent girls as young as 9 years & prevention of anogenital warts in females & males

Young adolescent girls as young as 10 years

Dose &route 0.5ml IM 0.5ml IM

Schedule 0, 2 & 6 months. minimum 4 wks interval bet 1st & 2nd &12 wks bet 2nd&3rd

0, 1 & 6 months.2nd dose bet 1 and 2 ½ months after the 1st dose.

Side effects Mild and transient local reactions at the site of injection i.e erythema, pain or swelling

same

Contraindications

severe allergic reactions to previous dose, severe acute illness, pregnant females

same

Protection 70% against cervical cancers 70% against cervical cancers

WHO POSITION HPV vaccination should be introduced into national

immunization programmes where prevention of cervical cancer is a public health priority,

the introduction is programmatically feasible and economically sustainable, and

where cost-effectiveness aspects have been duly considered.

JAPANESE ENCEPHALITIS

Indications:

Vaccination is recommended for travellers with extensive outdoor exposure (camping, hiking, bicycle tours, outdoor occupational activities, in particular in areas where flooding irrigation is practiced)

In rural areas of an endemic region during the transmission season.

It is also recommended for expatriates living in endemic areas through a transmission season or longer.

JAPANESE ENCEPHALITIS VACCINES

Currently, three types of JE vaccines in use:

1. Mouse brain-derived inactivated vaccine.2. Cell culture-derived inactivated vaccine and3. Cell culture-derived live attenuated vaccine.

No JE vaccine- WHO-prequalified

The Mouse Brain-derived Inactivated Vaccine: (MBD)

Produced in several Asian countries including India (Central Research Institute, Kasauli). So far, the only type of JE vaccine that is commercially available in the

international market. Safe, efficacious

JAPANESE ENCEPHALITIS VACCINES CONT…. Disdvantages of the MBD vaccine

Multiple doses ( 3 Primary + Booster) Expensive vaccine, complicated schedule, side effects Low availability - Production stopped by major manufacturers globally - CRI may also close down the production

Cell-culture-derived inactivated vaccine

Manufactured in China Based upon the Beijing P-3 strain High viral yields when propagated in primary hamster kidney cells. Formalin-inactivated vaccine, inexpensive

JAPANESE ENCEPHALITIS VACCINES CONT… Cell-culture-derived live attenuated vaccine 1988 Chinese vaccine based on a stable neuro-attenuated strain of the JE virus (SA-14-14-2). Licensed for use in South Korea, Nepal and Sri Lanka. Vaccination schedule- 2 doses administered 12 months apart in children aged 1–2 years and a booster at 6

years of age > 6 yrs- single dose

Immunogenicity- Children 6-7 years- single dose & Older children- immunized twice at intervals of one to three months: Ab - 83%–100%

Modest reduction in both seroconversion and Ab titre when measles vaccine co-administered with JE vaccine

JAPANESE ENCEPHALITIS VACCINES CONT… October 04, 2013, India’s first indigenously prodcued vaccine against Japanese

Ence.phalitis (JE).

National Institute of Virology, Indian Council of Medical Research and Bharat Biotech Ltd. jointly developed the vaccine— JENVAC-- under the public-private-partnership. 

To begin with, the programme will focus on five worst affected states— Assam, Bihar, Tamil Nadu, Uttar Pradesh and West Bengal.

be administered free of cost under the National Immunization Programme.

The vaccine, developed by Bharat Biotech, will be more expensive than the Chinese option.

The imported vaccine costs around Rs.20 per dose while Jenvac is likely to be priced around Rs.70 per dose.

WHO POSITION

With increasing availability of efficacious, safe and affordable vaccines, JE immunization should be integrated into the EPI programmes in all areas where JE constitutes a public health problem.

The most effective immunization strategy in JE-endemic settings is one time catch-up campaigns including child health weeks

SWINE FLU VACCINE/ PANDEMIC INFLUENZA A (H1N1) VACCINES:

INFLUENZA VACCINES 2 Types: Inactivated And Live Attenuated

Inactivated Vaccine: 2009-2010 influenza season (25th Feb. 2009) Trivalent Inactivated Vaccine (TIV): - Type A/Brisbane/59/2007 (H1N1) - Type A/Brisbane/10/2007 (H3N2) - Type B/Brisbane/60/2008

Indications – All children 6 months to 18 yrs > 50 yrs of age Long term hospital stay Pregnant women High risk e.g. aspirin therapy, chronic diseases,

haemoglobinopathies, immunosuppression, compromised resp.function

INFLUENZA VACCINES CONT… Vaccination schedule-

Northern hemisphere- December – MarchSouthern hemisphere- April - September TIV effective if given 2-4 months before exposure 6 months – 9 yrs: 2 doses 1 month apart, annually > 9 yrs – 1 dose annually

Dose and route of administration- 0.25 ml – paediatric and 0.5 ml – adults Intramuscular injection

Efficacy – varies with age, health status, similarity between vaccine strains with circulating strains

INFLUENZA VACCINES CONT… LIVE ATTENUATED INFLUENZA VACCINE (LAIV) 2003- USFDA Same 3 strains as TIV Temperature sensitive, cold adapted Replicate effectively in the mucosa of nasopharynx Efficacy- 87 % efficacy against culture confirmed influenza 27 % decrease in febrile otitis media Can be given anytime in influenza season Dose and route of administration- 5-8 yrs- 2 doses at least 6 wks apart 9-49 yrs- single dose 0.5ml Intranasal route, half dose in each nostril

INFLUENZA VACCINES CONT…

Adverse reactions-

Local- Swelling, erythema, induration Systemic- (not common) fever, chills, myalgia, rarely anaphylaxis

Contraindications - Severe allergic reaction to prior dose, Acute moderate to severe illness

Storage: 2 °C and 8 °C Must not be frozen Opened multidose vials – till expiry date

WHO POSITION Pregnant women should have the highest priority.

Additional risk groups to be considered for vaccination, in no particular order of priority, are children aged 6–59 months, the elderly, individuals with specific chronic medical conditions, and health-care workers.

Countries with existing influenza vaccination programmes targeting any of these additional groups should continue to do so and should incorporate immunization of pregnant women into such programmes.

Vaccines on clinical trials

MALARIA VACCINES

World’s most important parasitic disease No vaccine currently licensed for malaria

Challenges – Complex malarial parasite life cycle Each stage- immunologically distinct Perception- limited market potential

Asexual stage vaccines- Based on the Ag of Pf in man Reduce severe complicated malaria- ↓mortality and morbidity So, WHO research priority vaccinese.g. Synthetic Pf (Pfs) conjugate vaccines (Pfs 66) Recombinant protein based

vacines

MALARIA VACCINES CONT…

Sexual stage vaccines- Transmission blocking vaccines e.g. Pfs 25 conjugate vaccine

Pre-erythrocytic stage vaccines- Pre clinical stage e.g. radiation attenuated sporozoite vaccines, polypeptide DNA vaccines, circumsporozoite (CS) protein vaccines

VERY YOUNG TAKEN FOR TRAILS IN VIEW OF HIGH MORTALITY AND MORBIDITY Phase III trial will demonstrate

how the vaccine performs in two groups of children—one aged 6 to 12 weeks and a second aged 5 to 17 months—in different transmission settings across a wide geographic region in Africa.

MALARIA VACCINE POSSIBLE IN NEXT FEW YEARS

In Phase II testing, the vaccine reduced cases of malaria in young children 5 to 17 months by 53%.

If Phase III results are as good, the vaccine could be fully available in the next 5 - 10 years.

DENGUE VACCINES

4 types of dengue vaccines under clinical trials: Live tetravalent dengue vaccine Intertypic Chimeric vaccine (infectious clone technology) Chimeric vaccine Recombinant DNA vaccine

Intertypic chimeric vaccine- Structural genes from the DNA copy of an attenuated strain of dengue virus is replaced by the corresponding genes of a different dengue virus

serotype

Chimeric vaccine- Infectious clone technology Replaces the E gene of the 17D yellow fever (YF) vaccine with the analogous gene of the vaccine-targeted flavivirus

DENGUE VACCINES: CURRENT STATUS (2008)

HIV / AIDS VACCINES Challenges for vaccine development:

• Viral Genetic Diversity: HIV is not just one specific virus.• Immune Protection: We don’t know what immune responses are needed, or how

strong they need to be.• Neutralizing Antibody: Difficult to generate broadly neutralizing antibodies.• Vaccine Testing: Slow process, very expensive• Transmitted by mucosal route & infected cells• Time consuming & costly clinical trials

Vaccine approaches in development:

Subunit vaccine, Recombinant vector vaccine, Vaccine combination, Peptide vaccine, Virus-like particle vaccine (pseudovirion vaccine), Plasmid DNA vaccine (nucleic acid vaccine), Whole-inactivated virus vaccine, Live-attenuated virus vaccine

AIDS VACCINES CURRENTLY IN CLINICAL TRIALS Subunit Vaccines

- Recombinant envelope protein: gp 160, gp 120- Peptide: V3 peptide, T-B peptide

Live vector-based vaccines- Vaccinia envelope- Canarypox envelope

DNA vaccines

HIV / AIDS VACCINES CONT.. Preventive vaccines

Designed for people who are not infected with HIV If effective, would reduce risk of infection or viral load set

point after infection

Therapeutic vaccinesDesigned for people who are living with HIV If effective, would use the body’s immune system to help

control or clear HIV in the body

Luc Montagnier on Vaccine for AIDS

Our goal is not to completely eradicate the infection - that would be very difficult - but to produce a vaccine that will prevent not infection but disease. I think this is more possible.

It's clear that prevention will never be sufficient. That's why we need a vaccine that will be safe.

THE NEW GMO SWINE FLU CORN FLAKES Iowa State University

researchers are putting flu vaccines into the genetic makeup of corn, which may someday allow pigs and humans to get a flu vaccination simply by eating corn or corn products.

REFERENCES Weekly Epidemiological Records http://www.who.int/wer Vaccines update, www.cdc.gov www.gavialliance.com Arora, Textbook of Microbiology, 3rd Edn. New generation vaccines, levine & woodrow Vaccines , Plotkin Summary papers of Global Immunization Meeting New York, 17-19 Feb 200 Dengue Vaccine: The Current Status Maj MS Mustafa*, Lt Col VK Agrawal MJAFI 2008; 64 : 161-164

Albert Einstein said:“ We cannot solve today’s problems with the same

level of thinking that we were at when we created them.”

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