A multi-center, randomized, controlled, phase-2/3 study to evaluate the safety and immunogenicity of inactivated Japanese encephalitis vaccine in healthy ≥1 to <3 years old Indian children
DOI:
https://doi.org/10.18203/2349-3259.ijct20231104Keywords:
Children, Incidence, India, JE, Pediatric, Vaccine, Vaccine trialAbstract
Background: Japanese encephalitis (JE) is endemic in various parts of India. Due to the limited treatment options available, a new treatment option that is safe and effective is highly expected for the existing medical needs.
Methods: In the present randomized Phase-2/3 study, safety, immunogenicity, and reactogenicity of JE-vaccine manufactured by Biological E (BE-JE), given in 2-dose schedule, 28-days apart was assessed in 456 healthy ≥1 to <3-year-old children compared to a licensed JE-vaccine with 3-dose schedule manufactured by Green-cross-corporation (GCC-JE).
Results: The BE-JE group demonstrated non‑inferiority compared to GCC-JE group at day-56 as the lower confidence limit of the group difference was not ≥‑10%. At day-56, the geometric mean titre values were significantly higher in BE-JE group compared with the GCC‑JE group (217.97 vs 125.85; p=0.0023). No apparent difference was seen in the safety-profile between both vaccine groups, with all events reported being either mild or moderate in intensity. Also, no significant difference (p=0.2198) was reported in the number of subjects experiencing at least one adverse-event (AE) between both groups.
Conclusions: The present study demonstrated BE‑JE’s Vero-cell‑based inactivated JE-vaccine, administered in 2-dose schedule to be immunogenic, well-tolerated, and non-inferior, compared to GCC‑JE-vaccine, administered in a 3‑dose schedule in the pediatric Indian-population.
This study was prospectively registered with clinical trial registry of India bearing no CTRI/2011/091/000108 on 14/02/2011.
References
Singh Z, Agarwal VK. Japanese encephalitis: is routine immunization required? Med J Armed Forces India. 2005;61:357-9.
Miyake M. The Pathology of Japanese encephalitis. A review. Bull World Health Organ. 1964;30:153-60.
Saxena SK, Tiwari S, Saxena R, Mathur A, Nair MPN. Japanese encephalitis virus: The complex biology of an emerging pathogen. In: Tkachev S, editor. Encephalitis. Rijeka: Intech. 2013;10:162-80.
Dutta K, Rangarajan PN, Vrati S, Basu A. Japanese encephalitis: pathogenesis, prophylactics and therapeutics. Curr Sci. 2010;98:326-34.
Ghosh D, Basu A. Japanese encephalitis-a pathological and clinical perspective. PLoS Negl Trop Dis. 2009;3:e437.
Rao PN. Japanese encephalitis. Indian Pediatr. 2001;38:1252-64.
Kumar A, Sharma P, Shukla KK, Misra S, Nyati KK. Japanese encephalitis virus: Associated immune-response and recent progress in vaccine development. Microb Pathog. 2019;136:103678.
Hsieh JT, St John AL. Japanese encephalitis virus and its mechanisms of neuroinvasion. PLoS Pathog. 2020;16:e1008260.
Chatterjee P. Japanese encephalitis outbreak in India. Lancet Neurol. 2005;4:700.
Campbell GL, Hills SL, Fischer M, Jacobson JA, Hoke CH, Hombach JM et al. Estimated global incidence of Japanese encephalitis: a systematic review. Bull World Health Organ. 2011;89:766-74.
Quan TM, Thao TTN, Duy NM, Nhat TM, Clapham H. Estimates of the global burden of Japanese encephalitis and the impact of vaccination from 2000-2015. Elife. 2020;9:e51027.
Narain JP, Dhariwal AC, MacIntyre CR. Acute encephalitis in India: An unfolding tragedy. Indian J Med Res. 2017;145:584-7.
Parida M, Dash PK, Tripathi NK, Ambuj, Sannarangaiah S, Saxena P, Agarwal S, Sahni AK, Singh SP, Rathi AK, et al. Japanese encephalitis outbreak, India, 2005. Emerg Infect Dis. 2006;12:1427-30.
Gurav YK, Bondre VP, Tandale BV, Damle RG, Mallick S, Ghosh US et al. A large outbreak of Japanese encephalitis predominantly among adults in northern region of West Bengal, India. J Med Virol. 2016;88:2004-11.
Medhi M, Saikia L, Patgiri SJ, Lahkar V, Hussain ME, Kakati S. Incidence of Japanese Encephalitis amongst acute encephalitis syndrome cases in upper Assam districts from 2012 to 2014: A report from a tertiary care hospital. Indian J Med Res. 2017;146:267-71.
WHO, World Health Organization. WHO | Immunization country profile. Available at: https://apps.who.int/immunization_monitoring/globalsummary/incidences?c=IND. Accessed on 20 February 2023.
Muniaraj M, Rajamannar V. Impact of SA 14-14-2 vaccination on the occurrence of Japanese encephalitis in India. Hum Vaccin Immunother. 2019;15:834-40.
Solomon T, Dung NM, Kneen R, Gainsborough M, Vaughn DW, Khanh VT. Japanese encephalitis. J Neurol Neurosurg Psychiatr. 2000;68:405-15.
Kabilan L, Rajendran R, Arunachalam N, Ramesh S, Srinivasan S, Samuel PP, Dash AP. Japanese encephalitis in India: an overview. Indian J Pediatr. 2004;71:609-15.
Vashishtha VM, Ramachandran VG. Vaccination Policy for Japanese encephalitis in India: tread with caution! Indian Pediatr. 2015;52:837-9.
Tauber E, Kollaritsch H, Korinek M, Rendi-Wagner P, Jilma B, Firbas C et al. Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial. Lancet. 2007;370:1847-53.
Russell PK, Nisalak A, Sukhavachana P, Vivona S. A plaque reduction test for dengue virus neutralizing antibodies. J Immunol. 1967;99:285-90.
Heffelfinger JD, Li X, Batmunkh N, Grabovac V, Diorditsa S, Liyanage JB et al. Japanese encephalitis surveillance and immunization - Asia and Western Pacific regions, 2016. MMWR Morb Mortal Wkly Rep. 2017;66:579-83.
WHO. 2010. The immunological basis for immunization series: module 13: Japanese encephalitis. World Health Organization, Geneva, Switzerland. Available at: http://whqlibdoc.who.int/publications/2010/9789241599719_eng.pdf. Accessed on 12 February, 2023.
Kaltenböck A, Dubischar-Kastner K, Schuller E, Datla M, Klade CS, Kishore TSA. Immunogenicity and safety of IXIARO (IC51) in a Phase II study in healthy Indian children between 1 and 3 years of age. Vaccine 2010; 28:834-9.
Mort M, Baleta A, Destefano F, Nsubuga JG, Vellozzi C, Mehta U et al. Vaccine safety basics: learning manual. World Health Organization; 2013. Available at: https://apps.who.int/iris/handle/ 10665/340576. Accessed on 12 February 2023.
