Human Vaccine Science and Technology Status in India
India was one among leaders when vaccine research began to gain importance in the rest of the World and continues to do so even today despite some lag period during I & II World war and the following period till 1970s (Madhavi 2005). Several dedicated vaccine R&D institutions were set up between the 1950s-1980s with the help of Rockefeller foundation, UNICEF etc., and the real emphasis on vaccine research was initiated and promoted by the Department of Biotechnology (DBT) that was set up in 1986. In fact, DBT’s initiative gave tremendous boost to vaccine research and development (R&D) in this country and the following description and the table presents the evidence. However, these indigenous efforts have not yet been translated into appropriate use for Indian masses.
Vaccine R&D Institutions in India
There are around 26 vaccine R&D institutions in India that are actively engaged in research and development of vaccines, as of today. There are 2 institutes under DBT (came up in late 1980s), 11 under ICMR (came up between 1950s - 1990s), 6 under CSIR, and others include university departments and other autonomous institutions like AIIMS New Delhi, IISC Bangalore etc. (Table 1). Out of these Central Research Institute, Kasauli; Haffkine Institute (HI), Mumbai,; King Institute of Preventive Medicine, Chennai; and Pasteur Institute of India(PII), Coonoor are century old institutes that came up during British India. Their institutional structures are based on the innovation model where R&D and Production co-exist under the same roof. This was basically to facilitate research that would lead to vaccine development against a particular disease and transfer of technology to the production division. This model facilitated better and faster coordination between R&D and production divisions, for scaling up technology and other improvements and technological up-gradation. Rest of the research institutions that were set up after independence are dedicated to research and development of vaccines (Table 1).
Vaccine R&D status in India
Ideal vaccine is the one that has high protective efficiency with no or less side effects and can be affordable. Research is going on in the above mentioned institutions to develop an ideal vaccine against diseases such as cholera, TB, Hepatitis A, Hepatitis E, Hepatitis B, rotaviral diarrhoea, cervical cancer, pneumococcal infections, acquired immune deficiency syndrome, influenza, meningitis, filarial, rabies, typhoid, malaria, dengue, japanese encephalitis, leprosy etc. (Table 1). Efforts are on to use the modern tools of science and technology such as tissue culture, genetic engineering, construction of peptide/carbohydrate subunits and also unconventional delivery systems such as edible vaccines, nasal sprays, thermo-stable, slow release etc., basically to obtain the most purified uncontaminated antigens that can elicit high immune response, with no side effects. Currently, genetically engineered vaccines against HIV/AIDS, cholera, leprosy, malaria and TB (mycobacterium habana) were developed from indigenous strains and reached various stages of clinical trails. Basic research and development efforts are onto develop candidate molecules against HPV, rotavirus, edible cholera vaccine (edible, subunit), anti-rabies (tissue culture based) improved BCG vaccine, filarial, dengue, JE (tissue culture based, chimeric peptide), typhoid, HIV, filarial (recombinant), Pneumococcal (thermostable) and Hepatitis E (vaccine like particles). Out of these rotavirus vaccine, HIV/AIDS type C and malaria candidte vaccines have been developed under Indo-US bilateral programme called Indo-US Vaccine action Programme (Indo-US VAP), which was initiated in 1987 between India and US. Around 35 collaborative research projects have been funded so far to develop vaccines and diagnostics.
Table 1: Vaccine R&D profile in India
Organization |
Vaccines |
Current R & D Status |
International Centre for Genetic Engineering & Biotechnology (ICGEB), New Delhi |
Malaria |
Developed a malaria vaccine (p. vivox and p falciparum) and technology has been transferred recently. |
HIV/AIDs vaccine |
Basic R&D |
|
Dengue |
Developing a tetravalent dengue vaccine candidate |
|
Hepatitis E (VLP vaccine)
|
R&D |
|
HIV/AIDS (Recombinant vaccine) |
Phase-I, II clinical trial |
|
National Institute of Immunology (NII), New Delhi |
Tuberculosis (TB) |
Developing r-DNA based vaccine candidate molecule |
Human Papilloma virus (HPV) |
Developing vaccine candidates against HPV |
|
Typhoid |
Basic R&D |
|
Cholera |
Basic R&D |
|
JE (Tissue culture based) |
Basic R&D |
|
Leprosy (mw) immuvac |
Phase III clinical trail |
|
hcg-TT |
Phase III clinical trail |
|
Hepatitis C |
Basic R&D |
|
Pneumococcal vaccines |
Basic R&D |
|
National Institute of Virology (NIV), Pune |
Hepatitis A |
Vaccine candidate developed |
Rota virus |
Basic R&D |
|
Japanese encephalitis (Chimeric peptide vaccine) |
Basic R&D |
|
Typhoid
|
Basic R&D
|
|
Hepatitis C |
Basic R&D
|
|
HIV/AIDS Vaccine (subtype C) |
PhaseI, II, III clinical trial |
|
National Aids Research Institute (NARI), Pune |
HIV/AIDS Vaccine (subtype C) |
PhaseI, II, III clinical trial |
National Institute of Cholera and Enteric Diseases (NICED), Kolkata |
Indigenous HIV/AIDS (subtype C) |
PhaseI, II, III clinical trial |
V. Cholerea |
Phase I, II, III clinical trial |
|
Rota virus |
Basic R&D |
|
Typhoid |
Basic R&D |
|
Hib |
Basic R&D |
|
Tuberculosis Research Centre (TRC), Chennai |
Indigenous HIV/AIDS Subtype C Vaccine |
PhaseI, II, III clinical trial |
TB |
Basic R&D |
|
Regional Medical Research Centre (BBSR), Bhuvaneshwar |
Filariasis (a synthetic vaccine developed) |
Basic R&D |
Central Drug Research Institute (CDRI), Lucknow |
Cholera vaccine (subunit) |
Basic R&D |
Anti-leprosy vaccine (mycobacterium habana) |
Developed and undergone Phase I Clinical trial |
|
Anti-TB vaccine (mycobacterium habana) |
Being evaluated to be used in replacement of BCG vaccine |
|
Institute of Microbial Technology (IMTECH) ,Chandigarh |
Malaria |
Basic R&D |
Leishmaniasis |
Basic R&D |
|
Tuberculosis |
Basic R&D |
|
Cholera |
Phase I Clinical trials |
|
Centre for cellular and Molecular Biology (CCMB), Hyderabad |
Hepatitis B Vaccine |
Basic R&D |
Japanese Encephalitis |
Basic R&D |
|
Indian Institute of Chemical Technology (IICT), Hyderabad |
Hepatitis-B vaccine |
Developing Oral Delivery of Hepatitis B Vaccine |
mRNA-based cancer vaccine (new therapeutic agent in collaboration with Dabur) |
Phase II Clinical trial |
|
Synthetic peptide malaria vaccine |
Phase II Clinical trial |
|
Indian Institute of Chemical Biology (IICB), kolkata |
Oral vaccine for cholera |
Basic R&D |
Filariasis |
R&D to develop DNA vaccines |
|
All India Institute of Medical Sciences (AIIMS), New Delhi
|
Dengue |
Basic R&D |
Rotavirus Diarrhoea |
Phase 1 clinical trials |
|
VI Conjugated Typhoid Vaccine |
Development of vaccine candidates |
|
DNA/MVA-based HIV-1 Subtype C Vaccine |
Phase-I, II clinical trial |
|
Malaria vaccine |
Developing novel delivery system |
|
Indian Institute of Sciences (IISC), Banglore |
Tuberculosis |
Develop novel recombinant based candidate vaccine, |
Edible vaccine for cholera |
Basic R&D |
|
Rota virus Diarrhoea |
Basic R&D |
|
Anna University, Chennai |
Filariasis (recombinant DNA vaccine) |
R&D |
Mahatma Gandhi Institute of Medical Sciences (MGIMS), Wardha |
Filariasis (recombinant DNA vaccine) |
R&D |
Indian Immunologicals Ltd. (IIL), Hyderabad |
Combine DNA based Rabies vaccine |
R&D |
Sanjay Gandhi Post Graduate Institute of Medical Sciences, (SGPGIMS), Lucknow |
Cholera vaccine |
basic R & D and Phase I and II clinical trials |
Delhi university(DU), south campus |
BCG Vaccine |
Developing novel candidate vaccine |
Pasteur Institute of India, (PII), Coonoor |
Tetanus toxoid vaccine DPT vaccine DT |
R&D to improve yield of vaccines |
Haffkine Institute (HI), Mumbai |
Ant-rabies (duck embryo tissue culture) |
R&D |
Anti-Hiv vaccine |
R&D |
|
Influenza vaccine |
Clinical trials |
|
Tata Memorial Cancer Hospital (TMC), Mumbai |
HPV |
Phase I Clinical trial |
king Institute of preventive Medicine, Chennai |
DT ,TT, BCG |
R&D to improve yield of vaccines |
Central Research Institute (CRI), Kasauli |
Combination vaccine (DPT,DT,TT) |
Indigenous development |
Hyderabad University, Hyderabad |
TB |
Basic R&D |
Institute of Cytology & Preventive Oncology (ICPO), Delhi, (started in 1989) |
HPV |
Basic R&D |
Abbreviations: R&D –research & development; HIV-human immune virus; BCG- Bacillus Calmette-Guérin; DPT-Diphtheria Pertussis Tetanus; DT- Diphtheria toxoid; TT-Tetanus toxoid; HiB-Haemophilus influenzae type b vaccine; HPV-Human papilloma virus; VLP: Virus like proteins.
Source: compiled from the websites and annual Reports (2006-08) of DBT, ICMR, CSIR, Universities and Individual organizations.
Fig 1: Vaccine R&D map of India
Status of Vaccine R&D Achievements
Recent developments in the last one decade reveal that vaccine research appears to be high on the agenda and some of the following achievements are the highlights of Indian vaccine R&D:
Institutions like NIV, NII, AIIMS are actively engaged in identifying and developing several vaccine candidate molecules which are at different stages of development.
So far 10 institutions have developed around 12 vaccine candidate molecules and transferred the technology to industry (Table 2).
Out of these anti-lerprosy vaccine (immuvac) developed by NII has been transferred to Cadila ltd., Ahmadabad and the technology has been commercialised (Table 3).
-
The collobarative effort of three institutions named Institute of Microbial Technology (IMTECH), Chandigarh; National Institute of Cholera and Enteric Diseases (NICED), Kolkata; and Indian Institute of Chemical Biology (IICB), Kolkata; led to the indigenous development of a recombinant cholera vaccine based on local strain against cholera and currently it is undergoing phase II clinical trials. The technology has been transferred to Hyderabad based Shatha Biotech Ltd. (Table 1 & 2).
Indian Immunologicals Ltd., (IIL) Hyderabad, a public sector company also developed human anti-rabies vaccine indigenously and launched in the market in 2002 and it also supplies to Expanded Programme on Immunization (EPI).
NII developed a tissue culture based JE vaccine and NIV developed a synthetic peptide vaccine against Japanese encephalitis.
ICGEB is known to be actively involved in malaria vaccine research and the candidate vaccine molecules against P.vivax & P. falciparum are undergoing trials now. The technology has been transferred to Bharat Biotech international Ltd., Hyderabad.
-
Around 10 indigenous technologies (hepatitis B, typhoid, anti-rabies, DTP-HB, DTP-HB-Hib, mOPV type1, leprosy, hepatitis A) have been commercialized in the last one decade (Table 3). Prominent Indian companies that have commercialized vaccine technologies are Shantha Biotech ltd, BBIL, Hyderabad, Panacea Biotech, Cadila Pharma ltd., USV Biopharmaceuticals Mumbai, and Indian Immunologicals Ltd.(IIL), (public sector company).
Table 2: Vaccine Technologies Transferred to Industry
Vaccine Technology Developer |
Vaccine Developed |
Technology Transferred to |
Year of Transfer |
International Centre for Genetic Engineering and Biotechnology (ICGEB) New Delhi |
Malaria (P.vivax & P. falciparum) Development of malaria vaccine candidate antigens ICGEB New Delhi |
Bharat Biotech International Ltd., (BBIL) Hyderabad |
2001 |
National Institute of Immunology (NII), New Delhi |
Tissue culture based Japanese encephalitis vaccine Anti Leprosy vaccine (mw) immuvac |
Panacea Biotech, New Delhi
Cadila Pharmaceuticals, Ahmedabad |
2004
1998 |
National institute of Virology (NIV), Pune |
Vaccine candidate against Hepatitis-A Chimeric T-helper B Cell peptide vaccine against Japanese Encephalitis virus |
Bharat Biotech International Ltd, (BBIL) Hyderabad Panacea Biotech, New Delhi
|
2003
2001 |
All India Institute of Medical Sciences (AIIMS), New Delhi |
Rotavirus Diarrhoea
VI-Conjugated Typhoid Vaccine
DNA/MVA-based HIV-1 Subtype C Vaccine |
BBIL & Shanta Biotechiques Ltd., (SBIL) Hyderabad,
USV Biopharmaceuticals Mumbai Panacea Biotech, New Delhi (Under negotiations) |
2002
2003
2004-05
|
Indian Institute of Sciences (IISC), Bangalore & IIL Hyderabad |
DNA Rabies vaccine for animals |
IIL, Hyderabad |
2004-05 |
Indian Immunologicals Ltd. (IIL) Hyderabad |
Combine DNA based Rabies vaccine |
Indian Immunologicals Ltd., (IIL) Hyderabad |
2005 |
Institute of Microbial Technology (IMTECH), Chandigarh, National Institute of Cholera and Enteric Diseases (NICED) Kolkata, Indian Institute of chemical Biology (IICB), Kolkata |
Recombinant Cholera vaccine |
SBIL, Hyderabad |
2004 |
International Aids Vaccine Initiative (IAVI), New Delhi |
HIV/AIDS vaccine |
GlaxoSmith kline, Merck & Co., Inc., Hoffmann - La Roche. Delhi, & Panacea Biotech, Delhi |
2005-06 |
Source: compiled from – annual report 2006-08 & Websites of DBT, ICMR, CSIR, and universities and other autonomous institutions and R&D organizations & http://www.nature.com/nbt/journal/v25/n4/fig_tab/nbt0407-403_T4.html HIV: Human Immune Virus, AIDS: acquired immune deficiency syndrome
Table 3: Vaccine Technologies Commercialised
Vaccine |
Brand name |
Technology Developed by |
Technology Commercialised by |
Year of launching in the market |
1. DTwP+ Hep B+ Hib (World’s first fully liquid vaccine)
2. DTP + Hib & DTP + Hep B
3. Monovalent Oral Polio Type 1 Vaccine |
Easy five
Easy Four & Ecovac
moPV type-1 |
Panacea Biotech, Delhi |
Panacea Biotech, Delhi |
12th Aug 2008 (UNICEF supplier)
Jan.2008
2005 |
1. Hepatitis B
2. DPT +Hep B |
Shan vac B
Shantetra' |
Shantha Biotech Ltd, Hyderabad |
Shantha Biotechniques Ltd., Hyderabad |
1997
2005 |
DTPw-HB |
Q vac |
Serum Institute of India, Pune |
Serum Institute Of India, Pune |
Jan 2005 |
Anti- leprosy vaccine |
Immuvac |
National Institute of Immunology(NII), New Delhi |
Cadila, Ahmedabad |
2003 |
1.Hepatitis B
2. Typhoid vaccine |
Revac B
TYPBAR® |
Bharat Biotech International Ltd., (BBIL) Hyderabad |
BBIL Hyderabad |
Oct. 1998
2003 |
Hepatitis-A |
Havrix |
National Institute of Virology (NIV), Pune |
BBIL Hyderabad |
2003 |
Combine DNA based Rabies vaccine |
|
Indian Institute of Sciences (IISC), Bangalore |
Indian Immunologicals Ltd. (IIL) Hyderabad |
2005 (Ready for commercialization) |
DNA/MVA Subtype-C vaccine against AIDS |
|
All India Institute of Medical Sciences(AIIMS), NewDelhi |
Panacea Biotech, Delhi |
2005 (Under negotiation) |
Vi conjugated typhoid vaccine |
Ty21 |
All India Institute of Medical Sciences, New Delhi |
USV Biopharmaceuticals Mumbai |
2003 |
Tissue culture based anti-rabies vaccine |
rabirix |
Bharat biotech International ltd., (BBIL)Hyderabad |
BBIL , Hyderabad |
Dec 2006 |
Abbreviations: DTwP: Diphtheria Tetanus and Wholecell pertussis; DTP: Diphtheria Tetanus and pertussis;
Hep B; Hepatitis B; Hib: Influenza type B; UNICEF: United Nations Childrens Fund
Source: Compiled from annual reports, websites of research organizations and companies company,
http://www.intec-online.net/uploads/tx_intec/Biotechnologie-Report,
http://icmr.nic.in/ipr/full_doc.pdf ,
http://dst.gov.in/whats_new/press_releases05/ministry.html,
http://www.financialexpress.com/news/AIIMStyphoid-vaccine-
http://www.domain-b.com/industry/pharma/2005/20050820_launche
Indian Vaccine manufacturing capabilities
In India vaccines are traditionally produced by public sector companies and by state sponsored organizations like in many parts of the World. However, globally there is a radical transformation of the industry and now significant vaccine business is in the private sector, which is growing at rapid rate. US vaccine market accounted for a negligible 0.3% and Indian market for 0.1% of the total pharmaceutical industry till 1980s (Madhavi 2007), now accounts for 2% of total global pharmaceutical industry. Currently, Indian vaccine market is estimated to be around US$ 900 million (www.rncos.com/Report/IM153.htm) and global vaccine market is around US$ 10 billion (United Press International) and expected to grow up to US$ 23 billion by 2012. Thus, vaccine market is growing rapidly and it is considered to be significant profit making business in the global pharmaceutical industry. In India too several new companies have come up in 1990s and several new companies have entered vaccine business (Table 5). Prominent among them are Serum institute of India Pune, Bharat Biotech International Ltd., Shantah Biotech Ltd., Hyderabad and Panacea Biotech, Delhi. Some of the companies market imported vaccines and some new companies have developed new vaccines indigenously. Details are presented in the following table.
Table 4: Vaccine Manufacturers in India
Vaccine Institute |
Year of establishment |
Vaccines/sera produced |
1. Serum Institute of India, Pune |
1966 |
TT (1972), DTP, tetanus anti-toxin, measles vaccine(1989), Rubella (1992) MR& MMR (1993), DTP-IPV(1985), r-HB(2001), BCG(2002), HDC rabies (2004), DTP-HB(2005), Hib (2007) |
2. Shantha Biotech, Hyderabad |
1993 |
r-Hb, DTP-HB (2005) and JE vaccine |
3. Panacea Biotech, Delhi |
1984 |
OPV, r-Hb, DTP-HB, DTP-Hib, DTP-HB-Hib |
4. Biological Evans Ltd.(BE), Hyderabad |
1953 |
DTP, TT, R-HB (2004) |
5. Cadila laboratories |
1952 |
Typhoid |
6. Bharat Biotech International Ltd.(BBIL ), Hyderabad |
1996 |
R-HB (without cesium chloride), typhoid, anti-rabies (2006) |
7. Zydus Cadila (a divison Zydus Biogene manufactures vaccines) |
1995 |
R-HB, typhoid, anti-rabies chicken pox vaccine |
8. Biovaccines Pvt. Ltd., Hyderabad |
1977 |
TT |
9. LG Life Sciences India Pvt. Ltd.(LGLS), |
2002 |
r-HB |
10. UniChem Laboratories Ltd., Mumbai |
1944 but ventured into biotech business in 2001 including vaccines |
r-HB |
1946 and marketed OPV in 1960-70 and new vaccines since 1984 (Hb vaccines to others) |
R-HB, typhoid, anti-rabies, varicella vaccine |
|
12. Solvay Pharma India Ltd.,(SPIL) Mumbai |
Since 2004 |
Markets Netherland’s Influenza vaccine |
13. Intas Biopharmaceuticals Ltd., Ahmedabad |
2000 |
r-HB |
14. Pfizer India Ltd. |
mid 1990s |
Markets r-HB made in USA and also shantha biotech’s Hb vaccine |
15. Wyeth India Ltd., Mumbai |
Started as ledrle lab ltd in 1947 and later changed its name to cynamid Uindia ltd and in 1962 and became Public sector. In 1998 3 copanies merged as Wyeth Ledrle lTd and in 2003 as Wyeth Ltd., a MNC company now. |
Markets Hib, DTP, prevenar since late 1990s |
16. Chowgule & Co. (India)
|
Late 1940s |
Triple antigen |
17. GSK India |
Established in 1924 used to produce vaccines and in 1970s it business is more on other medicines and in post 1990s ventured into new vaccines |
Varicella, DTP-HB, Hb, Hib conjugate, DPT, Hepatitis A, Hb-TT |
18. Sanofi Pasteur India Ltd., |
1997 |
Typhoid, hib, anti-rabies, varicella, OPV, combination vaccines, Pneumococcal, Hb, Hepatitis A, meningococcal |
19. Zydus Cadila healthcare ltd., Ahmadabad |
|
Varicella,typhoid, |
20. Chiron Behring vaccines Ltd., Ankelswar India |
In 1978, and Hoecst sold its rabies manufacturing unit to Chiron Behring vacs India ltd., and taken over by Aventis and now by Sanofi pasteur |
Markets all new vaccines |
21. Bharat Serums and vaccines Private ltd.(BSV), |
1971 |
In1970s produced DPT group of vaccines and in 1990 markets typhoid vaccine etc. |
22. Biomedical Private Ltd., Ghaziabad |
2000 |
OPV, typhoid |
23. Dano vaccine & Bio Hyderabad, |
2000 |
TT |
24. Prime vaccine Pvt. Ltd., Hyderabad |
2000 |
TT |
25. Transgene biotech Ltd., Hyderabad |
2000 |
Typhoid |
26. B M pharmaceuticals Bhuveneswar |
1999 |
Suppliers of Anti-snake and anti-rabies liquid and freeze dried vaccines |
27. childcare Biotech Ltd., Jalgaon, Maharashtra |
2000 |
TT pertussis other vaccines |
28. Ruchi Networks, New Delhi |
Post 2000 |
Vaccine makers & suppliers Anti-cancer vaccines |
29.Ishitha Phrama Mumbai |
Post 2000 |
Vaccine makers & suppliers: Entire range of human vaccines like Polio, DTP, DTAP, Dual, Measles, MMR, Hepatitis A, Hepatitis B, BCG, Chicken Pox, Anti rabies, etc. Anti : HIV Vaccine Hepatitis A and combination vaccines |
30. Rajgarhia Drug Agencies, Ranchi |
1982 |
Vaccine distributors |
NOTE: HiB: influenza type b, TB: Tuberculosis, DPT: Diphtheria Pertusis Tetanus, HB: Hepatitis B, IBR: infectious bovine rhinotracheitis, HPV: human papillomavirus, BCG: Bacille Calmette-Guérin, OPV: Oral polio vaccine, DT: Diphtheria tetanus, MMR: Measles, mumps, and rubella, DTaP: Diphtheria tetanus Pertusis, TT: Tetanus toxide, AP: Alum Precipitated, BQ: Black Quarter, C-19: Cotton Strain-19, FD: Freeze Dried, GTV: Goat-adapted Tissue vaccine, HS: Haemorrhagic Septicaemia, OA: Oil Adjuvant, RP: Rinderpest and TCV: Tissue Culture Vaccine.
Source: Compiled from websites and annual reports of companies
http://pharmaceuticals.indiabizclub.com/directory/vaccines,
http://mohfw.nic.in/dofw%20website/family%20welfare%20programme/vaccines.ht
http//www.nature.com/nbt/journal/v25/n4/fig_tab/nbt0407-403_T4.html
References:
- Madhavi Y., 2005. Vaccine Policy in India. PLOS Medicine Weekly, May 2005, 2(5), e127, 0387-0391.
- Madhavi Y., 2006. New combination vaccines: Backdoor entry into India’s Universal Immunization Programme? Current Science, 10 June, 90 (11), 1465-1469.
- Madhavi Y., 2007. Transnational factors and national linkages: Indian experience in Human Vaccines. Asian Biotechnology and Development Review (ABDR), 9(2), 1-43.
- Steve Mitchell 2007., Global vaccine market to top 23 billion dollars, United Press International, Feb 8, 2007. http://www.terradaily.com/reports/Global_Vaccine_Market_To_Top_23_Billion_Dollars_999.html
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