Kyasanur Forest Disease – How far is a regulatory approved vaccine? 

Kyasanur Forest Disease (KFD) is a tick-borne viral hemorrhagic fever endemic to parts of India, particularly in Karnataka and neighboring states such as Kerala, Tamil Nadu, and Goa, along the Western Ghats. The KFD virus belongs to the Flavivirus genus within the Flaviviridae family. Its vectors commonly include Haemaphysalis spinigera, Dermacentor, and Ixodes ticks. The disease, also known as “monkey fever,” has a fatality rate of three to five per cent. Developing a more effective vaccine is therefore critical for public health.

A regulatory-approved KFD vaccine for humans is still several years away. While an older, formalin-inactivated vaccine existed (not formally approved by Indian authorities), it demonstrated limited efficacy and has been discontinued. The new and more promising vaccine candidate is being developed by Indian Immunologicals (Hyderabad) in collaboration with the Indian Council of Medical Research (ICMR)–National Institute of Virology (NIV), Pune.

A regulatory-approved KFD vaccine for humans is still several years away. While an older, formalin-inactivated vaccine existed (not formally approved by Indian authorities), it demonstrated limited efficacy and has been discontinued3 . The new and more promising vaccine candidate is being developed by Indian Immunologicals (Hyderabad) in collaboration with the Indian Council of Medical Research (ICMR)–National Institute of Virology (NIV), Pune.

This inactivated, adjuvanted vaccine—based on KFD virus strain NIV 164187 isolated by ICMR–NIV—is scheduled to enter Phase 1 clinical trials in India before the end of 2025.

As of October 2025, the inactivated KFD vaccine candidate has completed preclinical single- and repeat-dose toxicity and immunogenicity studies. Based on these data, the vaccine was found to be safe, well-tolerated, and immunogenic. The sponsor has proposed a first-inhuman study involving two doses (≥18 μg per dose), administered 28 days apart in healthy volunteers (aged 18–49 years) residing in endemic areas. The trial will assess seroconversion rates as the primary endpoint, with exploratory analyses comparing immunogenicity among subgroups stratified by baseline flavivirus serostatus. Participants will be followed for 366 days for safety and immunogenicity outcomes. A Data and Safety Monitoring Board (DSMB) report will be submitted after 57 days to the Central Drugs Standard Control Organisation (CDSCO) before initiating Phase II trials. The vaccine candidate is currently undergoing developmental and reproductive toxicology (DART) studies. Recruitment of female volunteers will commence after DART completion. 

Until 2022, a formalin-inactivated vaccine produced by the Karnataka Government’s Institute of Animal Health and Veterinary Biologicals (IAHVB) was used in endemic areas. However, it was discontinued due to several major drawbacks:

◆ Limited efficacy: Protection was moderate and waned over time. 

◆ Production challenges: The vaccine was derived from a mouse brain–passaged virus, leading to supply constraints. 

◆ Strain mismatch: Circulating KFDV strains diverged genetically from the strain used in vaccine production, reducing effectiveness. 

◆Regulatory noncompliance: The vaccine and its manufacturing facility did not meet current Good Manufacturing Practice (cGMP) standards and lacked CDSCO approval.

The earlier vaccine showed 62.4 per cent efficacy with two doses and 82.9 per cent with boosters, but waning immunity and production issues limited its usefulness. Due to suboptimal protection, it was discontinued in October 2022. Recent approaches—including vesicular stomatitis virus (VSV)-based live-attenuated platforms, subunit vaccines targeting recombinant envelope domain III, and in silico-designed multi-epitope constructs—have shown promising immunogenicity and protection in preclinical models.

Developing a regulatory-approved KFD vaccine presents several technical and clinical challenges. KFD occurs sporadically; in 2024, Karnataka reported 2,567 suspected cases, of which 103 were confirmed 14,15. Transmission peaks between January and April16, and by mid-2025, 175 confirmed cases had been reported17. Conducting a full-scale Phase III clinical trial is challenging because vaccine efficacy must be evaluated while the virus is actively circulating— something that occurs only during limited seasonal windows. Thus, completing such trials could take several years.

Women living near the Western Ghats are particularly vulnerable, as they often enter forested areas for firewood collection and other livelihood activities, exposing them to Ixodes ticks that transmit KFDV from infected bonnet macaques. Considering the complications observed in other flavivirus infections (e.g., dengue, Zika), DART studies are critical for demonstrating vaccine safety in female laboratory animals. Given the urgent need for a regulatory-approved KFD vaccine, emergency authorisation by Indian authorities may be considered based on Phase I and II clinical data, supported by nonhuman primate challenge studies (bonnet macaques) and DART results from two animal species.

Another major constraint in developing a fully regulatory compliant KFD vaccine is its limited commercial potential. Between 2000 and 2018, IAHVB produced 1.28 million doses at a cost of Rs 20–30 ($0.22–0.33) per dose18. The estimated annual domestic demand is approximately 0.5 million doses, with virtually no private market. The government would likely remain the sole purchaser, using the vaccine for annual immunisation in high-risk areas or maintaining stockpiles for emergency use.

References:

1. Pattnaik P (2006) Kyasanur forest disease: an epidemiological view in India. Rev Med Virol 16(3):151-165. https://doi.org/10.1002/rmv.495 
2. Rajaiah P (2019) Kyasanur Forest Disease in India: innovative options for intervention. Hum Vaccin Immunother 15(10):2243-2248. https://doi.org/10.1080/21645515. 2019.1602431. 
3. Bohra B, Srivastava KS, Raj A, Pal N, Shukla R (2025) Kyasanur Forest Disease Virus: Epidemiological Insights, Pathogenesis, Therapeutic Strategies, and Advances in Vaccines and Diagnostics. Viruses 17(8):1022. https://doi.org/10.3390/v1708102 2 
4. Gireesh Babu (2025) SEC recommends approval for phase I clinical trial of KFD vaccine from IIL. 06 October 2025. https://www.pharmabiz.com/Ne wsDetails.aspx?aid=181662&sid =1. Accessed on 06–10–25 
5. Minutes of the Meeting of Subject Expert Committee (SEC) – Vaccine to review proposals and advice Drugs Controller General (India) in matters for Biologicals & PAC proposals held on 24.09.2025. https://cdsco.gov.in/opencms/ope ncms/system/modules/CDSCO.WEB/elements/common_do wnload.jsp?num_id_pk=Mjc3M A==. Accessed on 06–10–25 
6. Pattnaik S, Agrawal R, Murmu J, Kanungo S, Pati S (2023) Does the rise in cases of Kyasanur forest disease call for the implementation of One Health in India? IJID Regions 7:18-21. https://doi.org/10.1016/j.ijregi.20 23.02.003 
7. Systemic Failures Led to Ineffective KFD Vaccine Being Used for Decades: Report (2022) Science the Wire. https://science.thewire.in/health/kfd-vaccine-karnataka-drugregulation-failure/. Accessed on 06–10–25 
8. Dandawate CN, Desai GB, Achar TR, Banerjee K (1994) Field evaluation of formalin inactivated Kyasanur forest disease virus tissue culture vaccine in three districts of Karnataka state. Indian J Med Res 99(4):152–158. PMID: 7927566. 
9. Kasabi GS, Murhekar MV, Sandhya VK, Raghunandan R, Kiran SK, Channabasappa GH, Mehendale SM, Bausch DG (2013) Coverage and effectiveness of Kyasanur forest disease (KFD) vaccine in Karnataka, South India, 2005–2010. PLoS Negl Trop Dis 7(1): e2025. https://doi.org/10.1371/journal.p ntd.0002025 
10. Bhatia B, Tang-Huau T-L, Feldmann F, Hanley PW, Rosenke R, Shaia C, Marzi A, Feldmann H (2023) Single-dose VSV-based vaccine protects against Kyasanur Forest disease in nonhuman primates. Sci Adv 9: eadj1428. https://doi.org/10.1126/sciadv.adj 1428 
11. Bhatia B, Meade-White K, Haddock E, Feldmann F, Marzi A, Feldmann H (2021) A live-attenuated viral vector vaccine protects mice against lethal challenge with Kyasanur Forest disease virus. NPJ Vaccines 6(1):152. https://doi.org/10.1038/s41541- 021-00416-2 
12. Das M, Kumar V, Madhukalya R, Gupta R, Agarwal V, Choudhary S, Bhutkar M, Tomar S, Kumar D, Kumar R (2025) Purification and characterization of kyasanur forest disease virus EDIII domain of major envelope glycoprotein. J Virol Methods 333: 115089. https://doi.org/10.1016/j.jviromet.2024.115089 
13. Arumugam S, Varamballi P (2021) In-silico design of envelope based multi-epitope vaccine candidate against Kyasanur forest disease virus. Sci Rep 11:17118. https://doi.org/10.1038/s41598- 021-94488-8 
14. Srilekha N, Kandi V, Sri Ram G, Jayashankar CA, Harshitha A, Akshay AS, Challa K, Pratyusha SP (2024) Kyasanur Forest Disease: A Comprehensive Review. Cureus 16(7): e65228. https://doi.org/10.7759/cureus.65 228 
15. Nikhil KC, Soumajit S, Patel SKumar, Aderao GN, Kanaka KK, Agrawal AN, Kiran NA, Tlha BE (2024) Battling Kyasanur forest disease: the race for robust and long-lasting Kyasanur forest disease vaccine. Intl J Surgery Global Health 7(6):e00496. https://doi.org/10.1097/GH9.000 0000000000496 
16. Kumar JS, Yadav PD, Shete AM, Majumdar T, Patil S, Dash PK (2021) Intl J Infect Dis 112(11):346-351. https://doi.org/10.1016/j.ijid.2021. 01.041 
17. Weekly Infectious Disease Report, 01 January to 28 September 2025, Commissionerate – Health & Family Welfare Services, State Surveillance Unit, Government of Karnataka, India. 28 September 2025. https://hfwcom.karnataka.gov.in/uploads/39%20ID SP%20Weekly%20Infectious%20Diseases%20Report_1759487331.pdf. Accessed on 06–10–25 
18. Sunitha RR (2018) Bengaluru lab steps up production of vaccines for monkey fever. 20 March 2028. http://timesofindia.indiatimes.com/articleshow/63372226.cms. Accessed on 06–10–25 

(About the author: Honorary Scientific Advisor to multiple Indian Biotech Start-ups, and Professorof-Practice (Honorary), KIIT Deemed-to-Be University, Bhubaneswar)