Newer Vaccine: Advancements in Immunization

Detailed presentation on Newer vaccines with Advancements in Immunisation, mRNA vaccines, Vaccines developed after 2000 covid vaccines

1. NEWER VACCINES ADVNCEMENTS IN IMMUNIZATION Presented by Dr. Sainath Gore Junior Resident, Department of Community Medicine, Guide Dr. S.D. Kotnis Associate Professor Department of Community Medicine,

2. 1. INTRODUCTION HISTORY. CONCEPT OF NEWER VACCINE. HOW IT WORKS. 2. NEED AND NECESSITY NEWER OF VACCINE . 3. NEWER VACCINE. i . RECENTALY DEVELOPED VACCINE ii. DEVELOPING VACCINE iii. FUTURE VACCINE CONTENTS

3. History “With the exception of safe water,no other intervention,not even antibiotics,has had such a major effect on mortality reduction”

4. EDWARD JENNER 1796 Edward Jenner was an English physician and scientist who pioneered the concept of vaccines and created the smallpox vaccine, the world's first vaccine

5. In China, a method of acquiring immunity from smallpox by collecting biological samples from smallpox patients was developed relatively early in history. Although it is believed that the variolation method was introduced from India to China in the 11th century [ 1 ],  Douzhen Xinfa  (Essential knowledge and secrets of pox diseases),, which Manjeon published in 1549, is believed to be the oldest record of the variolation method in China. During the Ming Dynasty ( Longqing , 1567–1572), the variolation method was further developed in Huangshan City, and this area became the center of variolation in China [ 2 ]. VARIOLATION

6. THE VACCINE STORY

7. “A Vaccine is an immuno-biological substance designed to produce specific protection against a given disease.” A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe. Vaccines may be prepared from live modified organisms, inactivated or killed organisms, extracted cellular fractions, toxoids or combination of these. The word “ Vaccine ” comes from the cowpox virus vaccinia which derives from the Latin word vacca for cow . WHAT IS A VACCINE?

8. Vector to TYPES OF VACCINES

9. Live Attenuated Vaccines Microorganisms can be attenuated or disabled so that they lose their ability to cause significant disease (pathogenicity) but retain their capacity for transient growth within an inoculated host. The first vaccine used by Jenner is of this type. Inoculation of humans with vaccinia (cowpox) virus confers immunity to smallpox (without causing smallpox).

10. The pathogen is treated with heat or chemicals, killed making it incapable of replication, but allows it to induce an immune response to at least some of the antigens contained within the organism. It is important to maintain the structure of epitopes on the surface antigens during inactivation. Heat inactivation is often unsatisfactory because it causes extensive denaturation of proteins. Chemical inactivation with formaldehyde or various alkylating agents has been successful. The Salk polio vaccine is produced by formaldehyde inactivation of the poliovirus. Inactivated or “Killed” Vaccines

11. Subunit Vaccines contains only specific, purified macromolecules derived from the pathogen. It contains only the antigenic parts of the pathogen which are necessary to elicit a protective immune response. The three most common available subunit vaccines are inactivated exotoxins or toxoids capsular polysaccharides or surface glycoproteins key recombinant protein antigens. Subunit Vaccines

12. Some bacteria produce disease in their host by producing exotoxins. Toxoid Vaccines are inactivated exotoxins. The exotoxins are treated with heat/ chemicals to inactivate it. This makes them unable to cause the disease but can stimulate the body to produce antitoxoid antibodies which are capable of binding to the toxins and neutralizing their effects. Example : Tetanus, Diphtheria bacterial vaccines Toxoid Vaccines

13. The virulence of some pathogenic bacteria depends primarily on the antiphagocytic properties of their polysaccharide capsule. Coating the capsule with antibodies and/or complement greatly increases the ability of macrophages and neutrophils to phagocytose such pathogens. The current vaccine for Streptococcus pneumoniae consists of 13 antigenically distinct capsular polysaccharides (PCV13). The vaccine induces formation of opsonizing antibodies and it is on the list of vaccines recommended for all infants. The vaccine for Neisseria meningitidis , a common cause of bacterial meningitis, also consists of purified capsular polysaccharides. Capsular polysaccharide Vaccines

14. Live attenuated vaccines prolong antigen delivery and encourage cell-mediated responses, but have the disadvantage of reverting to pathogenic forms rarely. Recombinant vectors maintain the advantages of live attenuated vaccines while avoiding this major disadvantage. Individual genes that encode key antigens of especially virulent pathogens can be introduced into attenuated viruses or bacteria. The attenuated organism serves as a vector, replicating within the vaccinated host and expressing the gene product of the pathogen. Since most of the genome of the pathogen is missing, reversion potential is virtually eliminated. Recombinant vector Vaccines

15. A DNA vaccine, utilizes plasmid DNA encoding antigenic proteins that are injected directly into the muscle of the recipient. This strategy relies on the host cells to take up the DNA and produce the immunogenic protein in vivo, thus directing the antigen through endogenous MHC class I presentation pathways, helping to activate better CTL responses. The DNA appears either to integrate into the chromosomal DNA or to be maintained for long periods in an episomal form, and is often taken up by dendritic cells or muscle cells in the injection area. Tests in animal models have shown that DNA vaccines are able to induce protective immunity against a number of pathogens, including influenza and rabies viruses. The addition of a follow-up booster shot with protein antigen or inclusion of supplementary DNA sequences in the vector, may enhance the immune response. DNA Vaccines

16. Advantages of DNA vaccines: Since the encoded protein is expressed in the host in its natural form, there is no denaturation or modification. The immune response is directed to the antigen exactly as it is expressed by the pathogen, inducing both humoral and cell-mediated immunity. No refrigeration of the plasmid DNA is required, eliminating longterm storage challenges. In addition, the same plasmid vector can be custom tailored to insert DNA encoding a variety of proteins, which allows the simultaneous manufacture of a variety of DNA vaccines for different pathogens, saving time and money. Human trials are underway with several different DNA vaccines, for malaria, HIV, influenza, Ebola, and herpes virus, along with several vaccines aimed at cancer therapy. Although there are currently no licensed human DNA vaccines, three such vaccines have been licensed for veterinary use, including a WNV vaccine that is protective in horses.

17. mRNA vaccine

18. DNA vaccines Vs Traditional vaccines Uses only the DNA from infectious organisms. Avoid the risk of using actual infectious organism. Provide both Humoral & Cell mediated immunity Refrigeration is not required Uses weakened or killed form of infectious organism. Create possible risk of the vaccine being fatal. Provide primarily Humoral immunity Usually requires Refrigeration. DNA vaccines Traditional vaccines

19. NEWER VACCINES ‘New’ is relative: New to the Immunization program New because of recent discovery New to the specific market or region (after Licensing) Introduction of a New vaccine may be Vaccine against a disease not previously covered by immunization New product formulation of a vaccine ( e.g.,a liquid vaccine replacing a lyophilized vaccine) New combination vaccine (e.g., DTP- HepB -Hib replacing previous individual vaccines) Vaccine that uses a new route of administration in place of a currently-used vaccine (e.g., an injectable vaccine)

20. NEED for Newer VACCINES

21. NEED for Newer VACCINES “ prevention is better then cure ” Emerging and Re-emerging Infectious Diseases : New infectious diseases continue to emerge (e.g., COVID-19), and some previously controlled diseases can resurge (e.g., measles). New vaccines are crucial to address these threats effectively. Evolution of Pathogens : Many pathogens, like influenza viruses, mutate rapidly, necessitating updated vaccines to maintain efficacy. Similarly, antibiotic-resistant bacteria require novel vaccine strategies to prevent infections. Unmet Medical Needs : Some diseases still lack effective vaccines (e.g., HIV, malaria). Research and development are needed to create vaccines that can protect against these challenging pathogens. Improved Efficacy and Safety : Advances in vaccine technology can lead to more effective and safer vaccines. For example, newer vaccines may offer longer-lasting immunity or require fewer doses. Global Health Equity : Developing vaccines that are affordable, easy to transport, and stable at various temperatures can improve access in low-resource settings, helping to reduce health disparities.

22. NEED for Newer VACCINES Changing Demographics and Health Conditions : Aging populations and the increase in individuals with chronic health conditions necessitate vaccines that are effective in these groups, who may have different immunological responses. Bioterrorism and Biosecurity : New vaccines are needed to protect against potential bioterrorism threats and to ensure biosecurity. This includes vaccines for pathogens that could be used as biological weapons. One Health Approach : Addressing zoonotic diseases (those that jump from animals to humans) requires vaccines for both humans and animals to prevent outbreaks at the source. Eg. Rabies vaccine Advances in Technology : Breakthroughs in vaccine technologies, such as mRNA vaccines, viral vector vaccines, and nanoparticle vaccines, open new possibilities for preventing diseases more efficiently and effectively. Pandemic Preparedness : The COVID-19 pandemic highlighted the need for rapid vaccine development and deployment. Developing platforms and infrastructures for quick response is vital for future pandemics.

23. NEWER VACCINE RECENTALY DEVELOPED VACCINE DEVELOPING VACCINE FUTURE OF VACCINES

24. How newer vaccines are developed

25. SOME RECENTALY DEVELOPED VACCINE Prevnar (pneumococcal conjugate vaccine) 2002 Flumist (1st live attenueted influenza vaccine ) 2003 1st killed Influenza vaccine 2004 Menatra (new meningococcal vaccine ) 2005 Rotateq (Rota vaccine) 2006 HPV vaccine (Gardasil)2006 Varivax (for chicken pox)2007 Flumist nasal vaccine of 1st live attenueted influenza vaccine Rotarix (rota virus vaccine) 2008 Influenza-A (H1N1) 2009

26. Pneumococcal Conjugate Vaccine (PCV) APPROVED BRAND- Prevnar 13 AGE- Children - 6 weeks to 5 years Adult - >50 INDICATION AND USAGE- Active immunization for invasive disease caused By streptococcus pneumoniae DOSAGE AND ADMINSTRATION- Children: The four-dose immunization series Consists of a 0.5 ml intramuscular injection administered at 2, 4, 6, and 12-15 months of age Adults 50 years and older: a single dose. CONTRAINDICATIONS :1. Allergy to contents 2. Premature baby 3. Immunocompromised

27. FLUMIST (Influenza Virus ) INDICATION AND USAGE- A gainst Influenza disease caused by Influenza Virus subtypes A and type B DOSAGE & ADMINISTRATION- CONTRAINDICATION : Hypersensitivity to eggs, egg proteins, gentamicin, gelatin, or arginine, or life-threatening reactions to previous influenza , oncomitant aspirin therapy in children and adolescents. .

28. Menactra (N.meningitidis ) INDICATIONS AND USAGE Menactra vaccine is indicated for active immunization to prevent i nvasive meningococcal disease c a u s e d b y N.me n i n g i t i d i s serogroups A, C, Y and W-135. Menactra is approved for use in individuals 9 months through 55 years of age. Menactra vaccine does not prevent N meningitidis serogroup B disease. DOSAGE AND ADMINISTRATION 0.5 mL dose for intramuscula r injection. • Children 9 to 23 months of age: Two doses, three months apart. • Individuals 2 to 55 years of age : A single dose. CONTRAINDICATIONS Severe allergic reaction (eg, anaphylaxis) after a previous dose of a meningococcal capsular polysaccharide-, diphtheria toxoid- or CRM197-containing vaccine, or to any component of Menactra vaccine.

29. Rota virus ROTARIX - ROTARIX is indicated for the prevention of rotavirus gastroenteritis caused by G1 and non-G1 types (G3, G4, and G9), ROTARIX is approved for use in infants 6 weeks to 24 weeks of age dose 1 ml, gap between 2 dose should be 1 month ROTATEQ It is a live, oral pentavalent vaccine that contains five rota viruses types. Dosage forms and strengths :- Rota- teq , 2 mL for oral use, is a ready-to-use solution of live reassortant rotaviruses, containing G1, G2, G3, G4 and P1A Age - Administered as a 3-dose series to infants between the ages of 6 to 32 weeks. The first dose of rotateq should be administered between 6 and 12 weeks of age, with the subsequent doses administered at 4- to 10-week intervals. The third dose should not be given after 32 weeks of age. CONTRAINDICATIONS: Hypersensitivity, History of Intussusceptions , Severe Combined Immunodeficiency Disease.

30. GARDASIL (H.P.V.) INDICATIONS AND USAGE :- Girls and women 9 to 26 years of age for the prevention of the following caused by HPV : - Cervical, vulvar, vaginal, and anal cancer & Genital warts (condyloma acuminata) Boys and men 9 to 26 year s of age for the prevention of the - Anal cancer & Genital warts (condyloma acuminata). DOSAGE AND ADMINISTRATION 0.5-mL suspension for i ntramuscular injection at the following schedule: 0, 2 months, 6 months . CONTRAINDICATIONS- Hypersensitivity, including severe allergic reactions to yeast (a vaccine component), or after a previous dose of GARDASIL

31. Varivax (against Varicella ) INDICATIONS AND USAGE :- VARIVAX is indicated for vaccination against Varicella in individuals 12 months of age and older. The duration of protection of VARIVAX is unknown; however, long-term efficacy studies have demonstrated continued protection up to 10 years after vaccination. DOSAGE AND ADMINISTRATION Children :- 12 months to 12 years of age should receive a 0.5-mL dose administered subcutaneousl y. If a second 0.5-mL dose is administered, it should be given a minimum of 3 months later. Adolescents and Adults :-Adolescents and adults 13 years of age and older should receive a 0.5-mL dose administered S.C. at elected date and a second 0.5-mL dose 4 to 8 weeks later . CONTRAINDICATIONS- Individuals with leukemia, lymphomas of any type, or other malignant neoplasm affecting the bone marrow or lymphatic systems.

32. Panenza & Humenza (H 1 N 1 ) Both vaccines are for influenza A H1N1 virus but basic difference is panenza is non-adjuvant and humenza is adjuvant vaccine, so humenza need less strenght of vaccine.

33. Measles-Rubella(MR) Vaccine India launched one of the world’s largest vaccination campaigns against Measles and Rubella with technical support from WHO on 5 th February, 2017 Launched in 5 states/UTs - Karnataka, Tamil Nadu, Puducherry, Goa and Lakshadweep covering nearly 3.6 crore children. The campaign is targeted at vaccinating more than 41 crore children in the age group of 9 months to less than 15 years over the next 2 years across the country MR vaccine has been introduced in routine immunization and has replaced measles vaccine, given at 9-12 months and 16-24 months of age, in selected states

34. Pediarix ( DTaP + IPV + HEP-B )2004 Diphtheria and Tetanus Toxoid and Acellular Pertussis Adsorbed , Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine Combined] . Recommended Schedule & DOSE : The primary immunization series for PEDIARIX is 3 doses of 0.5 mL, given intramuscularly, at 6- to 8-week intervals (preferably 8 weeks). The customary age for the first dose is 2 months of age, but it may be given starting at 6 weeks of age. Contraindications:- Hypersensitivity to any component of the vaccine, including yeast, neomycin, and polymyxin-B, is a contraindication

35. Proquad ( MMR + VARIVAX ) 2006 INDICATIONS AND USAGE :- ProQuad is a vaccine indicated for active immunization for the prevention of measles, mumps, rubella, and varicella in children 12 months through 12 years of age. DOSAGE AND ADMINISTRATION :- A 0.5-mL dose for subcutaneous injection only. The first dose is usually administered at 12 to 15 months of age. A second dose, if needed, is usually administered at 4 to 6 years of age. CONTRAINDICATIONS:- History of anaphylactic reaction to neomycin or hypersensitivity to gelatin or any other component of the vaccine. Primary or acquired immunodeficiency states. Family history of congenital or hereditary immunodeficiency.

36. RTS,S/AS01(MOSQUIRIX) ' RTS ' stands for 'repeat T epitopes' derived from the sporozoite protein; ' S ' stands for the S antigen derived from Hbs antigen; AS01 is a adjuvant RTS,S/AS01 – most advanced vaccine candidate against most deadly form of human malaria Plasmodium falciparum , with no protection against P. vivax malaria Reconstituted 0.5mL vaccine Administered by intramuscular injection into: antero-lateral thigh in 6-12 weeks age group, and left deltoid in 5-17 months age group

37. R21/Matrix-M  The World Health Organization (WHO) has recommended a new vaccine, R21/Matrix-M, for the prevention of malaria in children. : The R21 vaccine targets the plasmodium sporozoite, which is the first stage of the malaria parasite entering the human body. This is a key innovation compared to previous malaria vaccines. The R21/Matrix-M vaccine showed 74-77% efficacy in preventing clinical malaria in children aged 5-17 months over 6 months. At 1 year, the efficacy remained high at 77%. A recent trial across 4 African countries found the R21/Matrix-M vaccine to be well-tolerated and highly effective. Over 12 months, the vaccine had 75% efficacy at sites with seasonal malaria transmission and 68% efficacy at sites with perennial transmission. The vaccine was shown to significantly reduce the rate of malaria cases, preventing 868 cases per 1,000 children-years at seasonal sites and 296 cases per 1,000 children-years at standard sites.

38. Vaccine for Dengue

39. DENGUE VACCINE 43 World’s first vaccine against Dengue By Sanofi Pasteur – first licensed in December, 2015, in Mexico Registered for use in individuals 9-45 years of age living in endemic areas CYD-TDV – live recombinant tetravalent vaccine 3-dose vaccine given on a 0/6/12 month schedule only who had previously infected Not licensed to use in India ADE:Antibody-dependent enhancement ( DENGVAXIA )

40. COVISHIELD India approved the Emergency Authorisation against novel coronavirus —Covishield by Serum Institute of India Serum Institute of India , the world's largest vaccine manufacturer by volume, joined hands with British-Swedish drugmaker to produce 1 billion doses of its COVID-19 vaccine. The first 100 million doses of Covishield were being sold to the Indian government at a special price of ₹200 The local version of Oxford-AstraZeneca COVID-19 vaccine is known as COVISHIELD

41. Indigenous vaccine India's indigenous COVID-19 vaccine by Bharat Biotech is developed in collaboration with ICMR-(NIV). COVAXIN After successful completion of the interim analysis, Bharat Biotech received DCGI approval for Phase 3 clinical trials in 26,000 participants in over 25 centres across India. “Based on the feedback from the dry-run of vaccination drive, the health ministry is ready to introduce Covid-19 vaccine within 10 days from the date of emergency use authorisation,”

42. VACCINE PLATFORM DESCRIPTION Viral vector (Non-replicating) Inactivated virus TYPE OF VACCINE ChAdOx1-S - (AZD1222) Whole-Virion Inactivated SARS-CoV-2 Vaccine (BBV152) NUMBER OF DOSES 1-2 2 DOSING SCHEDULE Day 0 + 28 Day 0 + 14 ROUTE OF ADMINISTRATION IM IM DEVELOPERS AstraZeneca + University of Oxford Bharat Biotech International Limited MANUFACTURING COMPANY India +UK India CLAIMED EFFICACY 62% in two full doses,90% of those initially given half dose  60-70% COVISHIELD COVAXIN

43. Sputnik V - Third Covid-19 vaccine approved in India – is the world’s first registered based on well studied human adeno virus vector platform. It has been approved for use in 71 countries with a total population of 4 billion. Sputnik V has demonstrated 3-7 times less of a reduction in virus neutralizing activity against omicron as compared to other leading vaccines. SPUTNIK LIGHT

44. Caption iNCOVACC ® iNCOVACC ® is a nasal vaccine indicated for active immunization against SARS-CoV-2 virus infection developed by Bharat biotech. It has been approved for active immunization against SARS-CoV-2 virus infection for age ≥ 18 years. iNCOVACC ® is administered through the nose, as a 2-dose series, 4 weeks apart. A total of 8 drops (0.5 mL per dose), 4 drops are administered into each nostril. Single booster dose to individuals aged 18 years and above, at ≥6 months after completion of primary schedule of Covishield or Covaxin .

45. DEVELOPING VACCINE Hiv Vaccine Leprosy

46. HIV VACCINE In 1984, after the confirmation of the etiological agent of AIDS by scientists at the U.S. National Institutes of Health and the  Pasteur Institute , the United States Health and Human Services Secretary Margaret Heckler  declared that a  vaccine  would be available within two years. But still it is a dream.

47. The ineffectiveness of previously developed vaccines primarily stems from two related factors. First, HIV is highly mutable. Because of the virus' ability to rapidly respond to selective pressures imposed by the immune system,  Second, HIV isolates are themselves highly variable. HIV can be categorized into multiple  clades  and subtypes with a high degree of genetic divergence. Therefore, the immune responses raised by any vaccine need to be broad enough to account for this variability. Any vaccine that lacks this breadth is unlikely to be effective.

48. Challenges in HIV Vaccine Research 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

49. …but on the Brightside… Precedent from animal studies: Long-term control of infection in vaccinated monkeys Immune control of HIV-1: Infected individuals control infection Vaccine Trials: In progress

50. Vaccine Vector Platform Vaccine Approach : Genetic engineer, doctors characterize and optimize a viral vector system that can be used to deliver HIV antigen(s) to antigen presenting cells (APCs) and that could also improve immune responses to induce long-term immunological memory. Approach are-- Viral Vectors HSV-based Amplicon Vector Recombinant Adenovirus Type 5 Vector Bacteriophage Lambda Vector

51. Transgenic plants Transgenic plants  can be a convenient and efficient way to obtain HIV vaccine. Plant-based vaccines, which are easy to produce and administer, and require no cold chain for their heat stability are, in principle, suited to such a strategy. More recently, it has been shown that even highly immunogenic, enveloped plant-based vaccines can be produced at a competitive and more efficient rate than conventional strategies

52. Leprosy vaccine

53. A vaccine containing ICRC bacilli (which are cultivable leprosy derived mycobacteria probably belonging to M. avium intracellulare complex) was prepared in 1979 at the Cancer Research Institute, Mumbai[12]. Studies, both on humans and animals, show that the ICRC bacilli exhibit antigenic cross-reactivity with M.leprae with reference to both B and T cell antigens

54. FUTURE OF VACCINES Therapeutic cancer vaccine Biodefense and special pathogen vaccines

55. 1. Therapeutic cancer vaccine . A number of innovative vaccines are also in development and in use: Dendritic cell vaccines combine dendritic cells with antigens in order to present the antigens to the body's white blood cells, thus stimulating an immune reaction. These vaccines have shown some positive preliminary results for treating brain tumors. [9]

56. Vaccine for non infectious disease T-cell receptor peptide vaccines are under development for several diseases using models of   Valley Fever ,  stomatitis , and  atopic dermatitis . These peptides have been shown to modulate cytokine  production and improve cell mediated immunity.

57. Synthetic Vaccines Targeting of identified bacterial proteins that are involved in complement inhibition would neutralize the key bacterial virulence mechanism. [10] While most vaccines are created using inactivated or attenuated compounds from micro-organisms,  synthetic vaccines  are composed mainly or wholly of synthetic peptides, carbohydrates or antigens that will produced more strong immunity and can be expected to stay longer or life time.

58. Recent updates in national immunisation schedule Inactivated Polio Vaccine (IPV) : IPV has been introduced in UIP as part of Global Polio end-game strategy, to mitigate the risk associated with tOPV to bOPV switch. IPV was introduced in November 2015 initially in 6 states, which was expanded across the country by April 2016. Rotavirus vaccine (RVV) : RVV has been introduced to reduce mortality and morbidity caused by Rotavirus diarrhoea in March 2016. It has been introduced in 11 states (Andhra Pradesh, Haryana, Himachal Pradesh, Jharkhand, Odisha, Assam, Tripura, Rajasthan, Tamil Nadu, Madhya Pradesh and Uttar Pradesh). The vaccine will be expanded across the country in 2019-20. Measles Rubella (MR) vaccine : India is committed to the goal of measles elimination and rubella control and to achieve the goal MR vaccine was introduced in the country through a campaign mode in a phased manner in 2017. MR campaign target around 41 crore children in the age group of 9 months to 15 years (covering ⅓ of the total population of the country) followed by 2 doses in routine immunization at 9-12 months and 16-24 months. Rubella component is now under routine immunization as MR vaccine. .

59. Recent updates in national immunisation schedule Pneumococcal Conjugate Vaccine (PCV) : PCV has been launched in May 2017 for reducing Infant mortality and morbidity caused by pneumococcal pneumonia. It has been introduced in Bihar, Himachal Pradesh, Madhya Pradesh, 19 districts of Uttar Pradesh and 18 districts of Rajasthan. Tetanus and adult diphtheria (Td) vaccine : TT vaccine has been replaced with Td vaccine in UIP to limit the waning immunity against diphtheria in older age groups. Td vaccine to be administered to adolescents at 10 and 16 years of age and to pregnant women.

60. MISSION INDRDHANUSH Mission Indradhanush (MI) was launched in December 2014 and aims at increasing the full immunization coverage to children to 90%. Under this drive focus is given on pockets of low immunization coverage and hard to reach areas where the proportion of unvaccinated and partially vaccinated children is highest. A total of six phases of Mission Indradhanush have been completed covering 554 districts across the country. It was also identified as one of the flagship schemes under Gram Swaraj Abhiyan (16,850 villages across 541 districts) and Extended Gram Swaraj Abhiyan (48,929 villages across 117 aspirational districts). While the first two phases of Mission Indradhanush resulted in 6.7% increase in full immunization coverage in a year, a recent survey carried out in 190 districts covered in Intensified Mission Indradhanush (5th phase of Mission Indradhanush) shows 18.5% points increase in full immunization coverage as compared to NFHS-4 survey carried out in 2015-16.

61. New intiateves in vaccine management and logiostics Capacity building : National Cold Chain Training Centre (NCCTE), Pune and National Cold Chain  & Vaccine Management Resource Centre (NCCVMRC) -NIHFW, New Delhi have been established to provide technical training to cold chain technicians in repair & maintenance of cold chain equipment System Strengthening: National Cold Chain Management Information System (NCCMIS) to track the cold chain equipment inventory, availability and functionality.

62. e VIN Electronic Vaccine Intelligence Network ( eVIN ) rollout : The Government of India has rolled out an Electronic Vaccine Intelligence Network ( eVIN )system that digitizes the entire vaccine stock management, their logistics and temperature tracking at all levels of vaccine storage – from national to the sub-district. This enables program managers to have real time view of the vaccine stock position and their storage temperature across all the cold chain points providing a detailed overview of the vaccine cold chain logistics system across the entire country. eVIN system has been completed in 12 states in the first phase – Assam, Bihar, Chhattisgarh, Himachal Pradesh Gujarat, Jharkhand, Madhya Pradesh, Manipur, Nagaland, Odisha, Rajasthan, and Uttar Pradesh. Second phase is ongoing in 9 states – Andhra Pradesh, Daman & Diu, Dadra & Nagar Haveli, Goa, Karnataka, Maharashtra, Telangana, Tripura and Uttarakhand. eVIN is to be scaled up to entire country.

63. VACCINE DELIVE RY SYSTEMS

64. SINGLE SHOT VACCINE In traditional vaccines are requires booster dose and repeated dose to induced immunity. . Single shot vaccines are given for preventing four to six diseases with only one injection. These disadvantages have spurred the development of single shot vaccine that can provide protection against infection with only one injection

65. TRANSDERMAL VACCINE DELIVERY SYSTEM The transdermal drug delivery system is a technique that provides drug absorption via the skin. Skin is known to be the highly immunogenic site for vaccination. Transdermal delivery is one of the needle free method of vaccine delivery.

66. Jet injector uses either spring mechanism or it consist of pressurised gases in a small cartridge or large canister form to force the aerosolized drug into the solution or through the skin either directly into the muscle or into the subcutaneous or intradermal layers. A high enough pressure can be generated by a fluid in intimate contact with the skin, then the liquid will punch a hole in to the skin and be delivered in to the tissues JET INJECTORS

67. MICRONEEDLES It consist of pointed micro sized projections fabricated into arrays up to hundred needles to penetrate the skin surface thereby allow the vaccine delivery. It is made of titanium or silicone. There are several approaches for the delivery of vaccines by the microneedles namely: Poke and patch method Coat and poke method Poke and release method Poke and flow method

68. INTRANASAL VACCINE DELIVERY Nasal administrations of vaccines have been shown to achieve a better systemic bioavailability and protection from gastric enzymes compared with parenteral and oral administration. Thus increasing the general efficacy of the vaccine Nasal immunization does not require needles and syringes

69. ORAL VACCINE DELIVERY Oral vaccination is the preferred route for patients, it is easy to administer to all ages of patient. Oral vaccination is much easier to arrange for large-scale vaccination programs. There are examples of oral administration of oral polio.

70. The lungs are a good target for vaccine administration due to their large surface area and the presence of large numbers of antigen-processing alveolar macrophages and dendritic cells. There are a variety of delivery devices for achieving drug delivery to the lungs, including inhalers and nebulizer. eg -BCG Vaccine INTRA PULMONARY VACCINE DELIVERY

71. MUCOSAL VACCINE DELIVERY SYSTEM Mucosal surface area is major portal of entry for many human pathogens that are the cause of infectious disease worldwide. Immunization by mucosal routes may be more effective at inducing protective immunity against mucosal pathogens at their site of entry. Discovery of safe and effective mucosal adjuvants are also being sought to enhance the magnitude and quality of the protective immune response. It is estimated that 70% of infectious agents enter the host by mucosal routes.

72. DESIGN AND STRATERGIES FOR MUCOSAL DELIVERY EMULSION TYPE DELIVERY LIPOSOME BASED DELIVERY POLYMERIC NANO PARTICLES VIROSOMES MELT IN MOUTH STRIPS

73. Sr.no Name of vaccine unit and address Licensed Vaccine 1 Bharat biotech International Ltd , Genome Valley, Turka-pally (V), Shameerpet Mandal, Ranga Reddy District, Hyderabad Hib, Rabies, bOPV, mOPV, DTP+Hib+HepB, Vi polysaccharide Typhoid, H1N1, DTP, DTP+HepB, Rotavirus vaccine, Inactivated JE vaccine, Typhoid+TT Conjugate Vaccine & DTP+Hep- B+Hib (Liquid), DTP+Hib 2 Biomed Pvt. Ltd, C-96, B.S. Road, Industrial Road, Ghaziabad- 201009. Hib, Meningococcal Polysaccharide (A,C, Y,W 135), bOPV, Vi Polysaccharide Typhoid Vaccine & Meningococcal polysaccharide (A & C), Rabies 3 Cadila healthcare , Sarkhej Bavla, NH No. 8-A, Moraiya, Sanand, Ahmedabad (Guj. Rabies vaccine, Bulk Rabies vaccine 4 Chiron Behering , Plot No. 3502, Post Box No. 136, GIDC, Estate, Ankleshwar, Bharuch (Guj.) Rabies vaccine 5 Green signal BioPharma Ltd , 49, Pappankuppan Village, Gummidipoondi, Chennai–601201 BCG Vaccine 6 Ranbaxy Lab , Sy. No.16, Ekarajapura, Siddlaghatta Road, Hasigila Post, Hoskote, Bangalore-562114 Typhoid polysaccharide & Hib Conjugate vaccine 7 Serum Institute of India, 212/2, Hadapsar,Pune- 411028 DTP, TT, DT, Hep-B, Hib (Vaccine & bulk), MMR, Measles, Rubella,BCG,     Rabies,  IPV, DTP+Hep B+Hib (Liquid +lyophilized), DTP+HepB, DTP+Hib, H1N1, Meningococcal A conjugate (Freeze dried), Mumps, MR, H1N1(whole virion inactivated), Measles +mumps, Measles+ Rubela, Influenza, Vaccine seasonal, Diphtheria Vaccine (bulk),TT bulk, Pertussis bulk, Measles bulk, Mumps bulk, Rubella bulk & DT bulk & OPV vaccine, CRM 197 Bulk, DTP+ Hep B+ Hib Bulk List of Vaccine indigenous manufacturers in the private sector with address of sites and products:

74. Sr.no Name of vaccine unit and address Licensed Vaccine 1 BCG vaccine, Guindy , Chennai. BCG, Tuberculine 2 CRI, Kasauli, District Solan, HP. DTP, yellow fever, JE, TT, DT,
Concentrated DTP vaccine 3 Pasteur institute of India , Coonor- 643103, Nilgiris District, Tamil Nadu DTP, TT, DT & inactivated Rabies vaccine 4 BIBCOL , village- Chola, Dist- Bulandshahr, U.P bOPV 5 Haffkine , Acharya Donde Marg, Parle, Mumbai- 400012 mOPV & bOPV 6 HLL Biotech Ltd ., Ticel  Biopark campus, CSIR Road, Taramani, Chennai HLL Biotech Ltd., Ticel   Biopark campus, CSIR Road, Taramani , Chennai List of Vaccine indigenous Manufacturers in Government and PSU with address of sites and products:

75. “ Humanly Possible: Saving lives through immunization Theme for year 2024

76. K. PARK. , BOOK of social and preventive medicine,21 st edition, bhanot publication. Plotkin , book on vaccine http://www.niaid.nih.gov/topics/vaccines/understanding/pages/typesvaccines.aspx  J.K. Sinha & S. Bhattacharya.  A Text Book of Immunology . Academic Publishers. p. 318. ISBN 978-81-89781-09-5. Retrieved 16 March 2012.  Kim W, Liau LM (2010). "Dendritic cell vaccines for brain tumors".  Neurosurg Clin N Am   21  (1): 139–57.DOI:10.1016/j.nec.2009.09.005. PMC 2810429.PMID 19944973 http://www.cdc.gov/vaccinesafety/Vaccines/gbsfactsheet.html History of Vaccines — A  Vaccine History  Project of The College of  ... www. history of vaccines .org/ Timelines —  History  of  Vaccines www. history of vaccines .org/content/timelines/al (accessed on 5/7/2012)  "Monovalent" at  Dorland's Medical Dictionary Polyvalent vaccine at  Dorlands Medical Dictionary 11. Vaccines : HOME page for  Vaccines  and  Immunizations  site www. cdc .gov/ vaccines 12 . anonymous, literature description of menctra vaccine, 2012

77. 13. anonymous, literature description of prevnar vaccine, 2012 14. anonymous, literature description of proqud vaccine, 2012 15 . anonymous, literature description of menctra vaccine, 2012 anonymous, literature description of flumist vaccine, 2012 anonymous, literature description of panenza vaccine, 2012 Alarcon JB, Waine GW, McManus DP (1999). "DNA vaccines: technology and application as anti-parasite and anti-microbial agents".Adv. Parasitol. 42: 343–410.DOI:10.1016/S0065-308X(08)60152-9.PMID 10050276.  Robinson HL, Pertmer TM (2000). "DNA vaccines for viral infections: basic studies and applications". Adv. Virus Res. 55: 1–74.DOI:10.1016/S0065-3527(00)55001-5.PMID 11050940.  Tang, D.; Devit, M.; Johnston, S.A.; Others, (1992). "Genetic immunization is a simple method for eliciting an immune response". Nature356 (6365): 152–154.DOI:10.1038/356152a0.PMID 1545867.  Barnes, Kirsty (2004-06-07). "First positive results for DNA-based flu vaccine". in-PharmaTechnologist.  "Fort Dodge Animal Health Announces Approval of West Nile Virus DNA Vaccine for Horses". PR Newswire. 2005-07-18. Retrieved 2007-11-21.

78. 23. "CDC and Fort Dodge Animal Health Achieve First Licensed DNA Vaccine" . CDC . 2005-07-18. Archived from  the original  on 2007-08-20. Retrieved 2007-11-21. 24. Wolff JA, Dowty ME, Jiao S,  et al.  (December 1, 1992).  "Expression of naked plasmids by cultured myotubes and entry of plasmids into T tubules and caveolae of mammalian skeletal muscle" .  J. Cell. Sci. . 103  ( Pt 4)  (4): 1249–59. PMID   1487500 . 25.  Anderson RG, Kamen BA, Rothberg KG, Lacey SW (January 1992).  "Potocytosis: sequestration and transport of small molecules by caveolae" .  Science   255 (5043): 410–1. DOI : 10.1126/science.1310359 .  PMID   1310359 . 26. Casares S, Inaba K, Brumeanu TD, Steinman RM, Bona CA (November 1997)."Antigen presentation by dendritic cells after immunization with DNA encoding a major histocompatibility complex class II-restricted viral epitope". J. Exp. Med. 186(9): 1481 6. DOI:10.1084/jem.186.9.1481.  PMC 2199124.PMID 9348305. 27. http://www.aidsinfo.nih.gov/clinical-trials/, clinical trial on h.i.v. vaccine (accessed on 03/07/2012) 28. Vaccine trial on malaria, www.who.int/vaccine_research/.../Session3_loucq_presentation.pdf (accessed on 4/6/2012) 29. Bock, R. (2010). "The give-and-take of DNA: horizontal gene transfer in plants". Trends in Plant Science 15 (1): 11–22.DOI :10.1016/j.tplants.2009.10.001. PMID 19910236. 

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