Status of Outbreak Response Immunization in India

Overview

The World Health Organization guidelines in 1999 were negative¹ about outbreak response immunization (ORI) specifically for low-and-middle income countries. However, this trend has been reversed since the COVID-19 pandemic. With the discovery of safer and efficacious vaccines that can be produced indigenously also, cost-effectively, there is tremendous scope for ORI strengthened epidemic control.

WHO enlists pathogens needing urgent vaccine development which are classified² as:

1. 1. Requiring research- HIV-1, Hepatitis C, Group A streptococcus and Klebsiella pneumoniae
   2. For further development- CMV, influenza, leishmaniasis, non-typhoidal salmonella, norovirus, P. falciparum, Shigella and Staph. Aureus
   3. For approval, policy recommendation or introduction- Dengue, Group B streptococcus, extraintestinal pathogenic E. coli, TB, RSV

The Immunization Agenda³ (IA) 2030 was promulgated by the 73^rd WHA, 2020. It sought to scale-up COVID-19 vaccines in all countries based on the principle of equity. The purpose of the IA framework is to reduce zero-dose communities and continue existing vaccination drives apart from pandemic prophylaxis.

GAVI⁴ through its First Response Fund, emulated the principle of African vaccine Manufacturing Accelerator (AVMA), which allocated US$ 1.2 billion for over 10 years to develop vaccines. The First Response Fund has set aside US$ 500 million for early-stage Global Health Security response, as an effective Day Zero Financing Facility for Pandemics (DZF).

The Coalition for Epidemic Preparedness Innovations⁵ (CEPI) collaborated with the Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India, for self-sufficiency in vaccine development, biosecurity, maintain global competitiveness in the quality and quantity of vaccines, and facilitate access to vaccines and technology even if not developed in India. Such collaboration was termed, the Ind-CEPI Mission, approved on March 27^th, 2019, for 5 years. Ultimately vaccines were envisaged for Zika, COVID-19, Nipah, KFD, Chikungunya (support late-stage development, prequalification and access) and any other Disease X for rapid response platforms and vaccine development.

The Ind-CEPI Mission⁵ was being implemented by Biotechnology Industry Research Assistance Council (BIRAC), a Public-Sector Undertaking (PSU). A tripartite agreement was signed by CEPI, DBT and BIRAC to support the vaccine candidates for COVID-19 and Chikungunya inactivated vaccines. Partnerships for Accelerating Clinical Trials or PACT initiative was undertaken by DBT and Clinical development Services Agency (CDSA), under the Ind-CEPI Mission.

Moreover, Global Influenza surveillance and Response system⁶ (GISRS) was hampered due to Covid-19 pandemic. Also, WHO recommended 14 days interval between Covid-19 vaccination and other vaccines, but later contralateral limbs were immunized parallelly with both Covid-19 and influenza vaccine, reason being, not much evidence in spacing. AstraZeneca or BioNTech Covid-19 vaccines along with Influenza were recommended.

India approved the Oxford–AstraZeneca vaccine⁷, manufactured under license by Serum Institute of India under the trade name Covishield and Covaxin, Bharat Biotech. Joining these vaccines, the Sputnik V was marketed under the license of Dr. Reddy’s Laboratories, with additional production from Serum Institute of India. Moderna, Johnson & Johnson and ZyCoV-D (a vaccine locally developed by Zydus Cadila) and other vaccine candidates are also undergoing local clinical trials.

Monitoring and quality Control Stakeholders

The Central Drugs Standard Control Organization⁸ (CDSCO) under the Directorate General of Health Services (DGHS) in MoH&FW is the National Drug Regulatory Authority of India. Its headquarters are in Delhi, with 8 zonal offices, 6 sub-zonal offices, 13 port offices and 7 laboratories under its coverage across India. All states and UTs have a drugs control department for monitoring of drugs and vaccines. Central Drugs Laboratory is in Kasauli, and CDSCO performs quality control of vaccines.

WHO’s CEPI in COVID-19 vaccines identified 23 pre-defined adverse medically significant events (AESIs). The Immunization Technical Support Unit (ITSU) under the Technical Advisory Group is carrying out multiple site sentinel surveillance study for AESI, involving 16 medical colleges from a few of the 23 enlisted. Several immunoassay labs were set-up with global standards under CEPI, costing a huge revenue.

Scope

A Genetically Defined Human Associated Microbial Culture Collection⁵ (Ge-HuMic) Facility was established at the Regional Centre of Biotechnology: Translational Health Science & Technology Institute (THSTI), Faridabad. It acts as a repository of microbial cultures for research institutes, universities, and industries for Research and Development.

A public private partnership⁸ will mobilize resources in synchronization with experienced drug companies which may seek assistance from outside India establishments for research and development of prophylactic vaccines for public health emergencies (PHEs).

Conclusion

With the growing threat of pandemics and about 191 outbreaks of zoonotic infections being reported from 2009-13, India needs to enhance its capacity of immunizing animals and humans against outbreaks apart from RI with zero-day financing for indigenous manufacturing. This can be materialized with the collaboration from the private sector resources also. India has biosafety laboratories for storing diverse pathogens which can be marketed to foreign companies for the sake of vaccine development (already functioning). Mechanisms for swift vaccine development is a promising strategy for epidemic control in the immediate future of Public Health. Monitoring and quality control trials must be begun for enhancing our capacity for gauging pathogens like strains of Influenza A,B,C circulating cyclically in the country for timely vaccine production.

References

1. 1. K. Lisa Cairns, Robert T. Perry, Tove K. Ryman, Robin K. Nandy, Rebecca F. Grais, Should Outbreak Response Immunization Be Recommended for Measles Outbreaks in Middle- and Low-Income Countries? An Update, The Journal of Infectious Diseases, Volume 204, Issue suppl_1, July 2011, Pages S35–S46, https://doi.org/10.1093/infdis/jir072
   2. https://www.who.int/news/item/05-11-2024-who-study-lists-top-endemic-pathogens-for-which-new-vaccines-are-urgently-needed
   3. Implementing The Immunization Agenda 2030: A Framework for action through Coordinated Planning, Monitoring & evaluation, Ownership & Accountability, and Communications & Advocacy. WHO manual.
   4. Annual Progress Report 2023. GAVI.
   5. Union Minister Dr Jitendr Singh inaugurates Asia’s first health research related “Pre-Clinical Network facility” under Coalition of Epidemic Preparedness Innovations (CEPI). Available from: https://pib.gov.in/PressReleasePage.aspx?PRID=2033656.
   6. Covid-19 Vaccines. WHO evaluation report issues. October 1^st 2022.
   7. AEFI Surveillance and Response. Operational Guidelines. National Health Mission. MoH&FW. 2024.