1. Moderator – Prof. A. M. Mehendale
Newer Vaccines
Moderator – Prof. A. M. Mehendale

2. Framework: List of newer vaccines: Introduction Immunization Vaccine
Development of vaccines
Need for new vaccines
Regulation & testing of vaccines
List of newer vaccines:
HPV
Malaria
Pandemic -influenza A (H1N1)
Rotavirus
Cholera vaccine
Meningococcal
Japanese encephalitis
Yellow fever
Hepatitis A&B
Varicella
Haemophilus Influenza B
Pneumococcal
HIV vaccine

3. Introduction: Immunization:
Immunization is the process whereby a person is made immune or resistant to an infectious disease
Immunization is a proven tool for controlling and eliminating life-threatening infectious diseases
It is one of the most cost-effective health investments, with proven strategies that make it accessible to even the most hard-to-reach and vulnerable populations
It has clearly defined target groups, can be delivered effectively through outreach activities and does not require any major lifestyle change
typically by the administration of a vaccine

4. Vaccine Vaccine may contain
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.

5. Vaccine
Live attenuated vaccines: BCG, typhoid, oral polio, plague, yellow fever, measles, mumps, rubella
Inactiavted/ Killedvaccines: Typhoid, cholera, rabies, polio(salk)
Toxoids: Diptheria &tetanus
Immunoglobulins: Hepatitis A, rabies,
Immunobiological substance
Specific protection
Most powerful & cost effective disease prevention tool
Primarily for Prevention of infectious diseases now for non-infectious diseases (e.g. fertility, autoimmune disease & cancer)
Immunizing agents:

6. Immune Response
Vaccination stimulates the immune system with a particular agent (e.g. bacterium, virus, toxin) causing it to develop antibody against it and produces immunological memory.
Anything that stimulates an immune response, whether naturally or via vaccination is called an antigen.
Vaccinated individuals produce a much stronger immune response if they encounter the agent again and will have a much lower chance of developing disease.
Types of immune responses:
Cell-mediated
specific cells called cytotoxic T cells attack cells in the body that have become infected, and
Humoral
body develops antibodies that neutralize and help eliminate antigens in the blood, on epithelial surfaces and in tissues fluid

7. 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
Other - Anti-idiotypic vaccine
Dendritic cell vaccine

8. Milestones In Vaccines Development

9. 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

10. 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?

11. An ideal Vaccine Should have …
Good Immune response
Both cell mediated immunity and antibody response
Provide long lived immunity
Preferably single dose
Safety
Danger of reversion to virulence or severe disease in immuno-compromised
Stability
Organisms in the vaccine must remain viable in order to infect and replicate in the host
Vaccine preparations should be less sensitive to adverse storage conditions
Expense
Cheap to prepare

12. 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)

13. General WHO position on new vaccines
Vaccines 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.

14. Newer Vaccines

15. Human papilloma virus 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
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
Protection
70% against cervical cancers

16. Malaria vaccine: Mosquirix (RTS,S):
Recombinant protein-based virus-like particle malaria antigens on Hepatitis B particle
30% efficacy against clinical malaria, 57% efficacy against severe malaria
RTS,S induces production of Ab’s and T cells that interfere with the ability of the malaria parasite to infect humans
Based on normal timelines that could see Mosquirix reaching the market in 2012.
Mosquirix vaccine is currently in third - stage clinical trials, GlaxoSmithKline reported.
Mosquirix is being tested in  some 16,000 children and infants at 11 trial sites in seven countries.
(circumsporozoite protein

17. 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 doses
Schedule
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
Contra indications
Hypersensitivity, history of intussusception or intestinal malformations AGE febrile illness
Hypersensitivity, history of intussusception or intestinal malformations AGE, febrile ill

18. 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
2doses orally
Schedule
1wk apart
3 weeks before departure
Side effects
None
Contraindications
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.
Dukoral is a monovalent
vaccine based on formalin and heat-killed whole
cells (WC) of V. cholerae O1

19. Cholera vaccine: Vaccine Shanchol and mORCVAX
The 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 Shanchol
in India; mORCVAX is currently intended for domestic
use in Viet Nam, whereas Shanchol will be produced
for Indian and international markets.
Dukoral is a monovalent
vaccine based on formalin and heat-killed whole
cells (WC) of V. cholerae O1

20. 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

21. 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 departure
Children under 2 years of age are not protected by the vaccine
Travellers should opt (A, C, Y, W-135) than the bivalent vaccine
Conjugate 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.

22. 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.
Two types of JE vaccine are widely available
inactivated mouse-brain-derived vaccine (IMB)
cell-culture-derived live attenuated SA vaccine.

23. (1) Inactivated mouse-brain-derived
Dose: 0.5 or 1.0 ml for adults, 0.25 or 0.5 ml for children depending on age
Schedule: 3 doses given 0, 7 and 28days.If 2doses given preferably 4 weeks apart. Booster after 1 year and then 3-yearly
Before departure : At least two doses
(2) Cell-culture-derived live attenuated SA vaccine
Dose: Same, Single dose given
Booster: single booster dose given at an interval of about 1 year
Before departure: one dose
Contraindications:
Hypersensitivity to a previous dose of vaccine
pregnancy and immuno-suppression
Adverse reactions:
Occasional mild local or systemic reaction; occasional
severe reaction with generalized urticaria,
hypotension and collapse
Contraindications:
Hypersensitivity to a previous dose of vaccine, pregnancy and immuno-suppression
Adverse reactions:
Occasional mild local or systemic reaction; occasional
severe reaction with generalized urticaria,
hypotension and collapse

24. Yellow Fever Type of vaccine Live, attenuated (17D viral strain)
Number of doses
One priming dose of 0.5 ml (s/c or im)
Booster
10-yearly (if re-certification is needed)
Contraindications
Egg allergy, immunodeficiency from medication, disease or symptomatic HIV infection, hypersensitivity to a previous dose, pregnancy
Adverse reactions
Rarely, encephalitis or hepatic failure
Before departure
International certificate of vaccination becomes valid 10 days after vaccination
Recommended
All travellers to areas with risk of yellow fever transmission
Special precautions
Not for infants under 9 months of age; restrictions in pregnancy

25. Hepatitis B
Three doses given the first two doses are usually given 1 month apart, with the third dose 1–12 months later
Protection for at least 15 years and probably for life. Boosters are not recommended.
Because of the prolonged incubation period of hepatitis B, some protection will be afforded to most travellers following the second dose given before travel. The final dose should always be given upon return.
A rapid schedule of administration of Monovalent hepatitis B vaccine has been given day 0, 1 month 2 months. An additional dose is given 6-12 months after the first dose.
A very rapid schedule of administration of hepatitis B vaccine has been proposed day 0, 7 , 21 days. An additional dose is given at 12 months.

26. Hepatitis B
A combination vaccine that provides protection against both hepatitis A and hepatitis B should be considered for travellers potentially exposed to both organisms
This inactivated vaccine is administered as follows day 0,
1 month, 6 months.
A rapid schedule at day 0, 1 month and 2 months, with an additional dose at 12 months
Very rapid schedule with administration at day 0, day 7 and day 21 with a booster dose at 12 months

27. Hepatitis A Type 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

28. 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.

29. Varicella vaccine 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.

30. 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 months
Dose:
0.5 ml im ant.lat.aspect of thigh
Contra-indictaions:
Local pain, erythema, fever

31. Influenza vaccine two vaccines are available:
The inactivated killed Vaccine (2004)
2 doses 4 weeks apart recommended. Immunity lasts for 3-6 months so annual revaccination recommended.
Live attenuated influenza vaccine (2003)
Given only to healthy persons 5 to 49 yrs of age who are not in contact with severely immuno-suppressed persons
Intra nasally annually to optimize protection
The inactivated killed Vaccine
Live attenuated influenza vaccine
Both vaccines includes Two type A strains (eg H3N2 and H1N1) & One type B strain

32. Pandemic influenza A (H1N1) vaccines:
Pandemic influenza A (H1N1) vaccines are available for use since September 2009
Most of these vaccines are produced using chicken eggs, while a few manufacturers are using cell culture technology for vaccine production
Health care workers worldwide should be immunized as a first priority
A maximum of 4.9 billion doses potentially could be produced in 12 months.

33. Pneumococcal vaccine Pneumococcal conjugated vaccine (PCV7): 2000
-infants and toddlers (6 weeks to 9 years)
Pneumococcal polysaccharide vaccine (PV23):
widely licensed for use in adults and children aged >2 years who have certain underlying medical conditions.(Sickle cell disease, damaged spleen / spleenec-tomised , AIDS, disease affecting immune system, diabetes, liver ds. chronic lung & heart disease, who is on immunosuppresive therapy).
Dose: 0.5 ml
Schedule s/c or i.m
<6 months 3 doses (6, 10, 14wks)
7-11 months- 2 doses & booster after 1yr
12-23 months-2 doses
>24mnths single dose

34. Pneumococcal vaccine
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.

35. HIV Vaccine
The availability of safe, highly effective and accessible HIV vaccine
Phase III trial for evaluating the efficacy of an envelope GP120 candidate vaccine and GP160 vaccine are conducted.

36. Thank You!

37. References Weekly Epidemiological Records http://www.who.int/wer
Vaccines update,
Arora, Textbook of Microbiology, 3rd Edn.
New generation vaccines, levine & woodrow
Vaccines , Plotkin