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 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

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 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

Human papilloma virus vaccineVaccine Quadrivalent vaccine (2006)

VLPs for 6,11,16,18Bivalent 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 imSchedule 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

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 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

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 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 dosesSchedule 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 domesticuse in Viet Nam, whereas Shanchol will be producedfor 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

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.

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 ageSchedule: 3 doses given 0, 7 and 28days.If 2doses given preferably 4 weeks apart. Booster

after 1 year and then 3-yearlyBefore departure : At least two doses

(2) Cell-culture-derived live attenuated SA 14-14-2 vaccineDose: Same, Single dose givenBooster: single booster dose given at an interval of about 1 yearBefore departure: one dose

Contraindications:• Hypersensitivity to a previous dose of vaccine• pregnancy and immuno-suppressionAdverse 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 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

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