Download Newer Vaccines

Newer Vaccines
Moderator – Prof. A. M. Mehendale
Framework:
•
•
•
•
•
•
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
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 lifethreatening 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
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.
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,
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
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
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 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.
Newer Vaccines
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
Contraindicat severe allergic reactions to previous
ions
dose, severe acute illness, pregnant
females
same
Protection
70% against cervical
cancers
70% against cervical cancers
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.
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
Mild & transient symptoms of
gastrointestinal or respiratory tract gastrointestinal or respiratory
tract
Contra
indications
Hypersensitivity, history of
Hypersensitivity, history of
intussusception or intestinal
intussusception or intestinal
malformations AGE febrile illness malformations AGE, febrile ill
Cholera vaccine:
Vaccine
Indications/Age
Killed whole-cell vaccine DUKORAL, 2004
(cholerae 01 in combination with
recombinant B-sub unit of cholera toxin)
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.
Cholera vaccine:
Vaccine
Indications/Age
Shanchol and mORCVAX
The closely related bivalent oral cholera
vaccines based on serogroups O1 and O139.
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.
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 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.
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 14-14-2 vaccine.
(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 14-14-2 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
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
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.
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
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
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
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.
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
Dose:
• 0.5 ml im ant.lat.aspect of thigh
Contra-indictaions:
• Local pain, erythema, fever
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
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
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
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.
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.
Thank You!
References
•
•
•
•
•
Weekly Epidemiological Records http://www.who.int/wer
Vaccines update, www.cdc.gov
Arora, Textbook of Microbiology, 3rd Edn.
New generation vaccines, levine & woodrow
Vaccines , Plotkin