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
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 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.
Malaria vaccine: Mosquirix (RTS,S): • Recombinant protein-based virus-like particle malaria antigenson 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.
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
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
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 imant.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.
References • Weekly Epidemiological Records http://www.who.int/wer • Vaccines update, www.cdc.gov • Arora, Textbook of Microbiology, 3rdEdn. • New generation vaccines, levine & woodrow • Vaccines , Plotkin